Trial Outcomes & Findings for A Study to Evaluate the Efficacy and Safety of Faricimab (RO6867461) in Participants With Diabetic Macular Edema (YOSEMITE) (NCT NCT03622580)

Last Updated: 2025-07-11

Results Overview

Best Corrected Visual Acuity (BCVA) was measured on the Early Treatment Diabetic Retinopathy Study (ETDRS) chart at a starting distance of 4 meters. The BCVA letter score ranges from 0 to 100 (best score), and a gain in BCVA letter score from baseline indicates an improvement in visual acuity. For the Mixed Model for Repeated Measures (MMRM) analysis, the model adjusted for treatment arm, visit, visit-by-treatment arm interaction, baseline BCVA (continuous), baseline BCVA (\<64 vs. ≥64 letters), prior intravitreal anti-VEGF therapy (yes vs. no), and region of enrollment. An unstructured covariance structure was used. Treatment policy strategy (i.e., all observed values used) and hypothetical strategy (i.e., all values censored after the occurrence of the intercurrent event) were applied to non-COVID-19 related and COVID-19 related intercurrent events, respectively. Missing data were implicitly imputed by MMRM. Invalid BCVA values were excluded. 97.5% CI is a rounding of 97.52% CI.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

940 participants

Primary outcome timeframe

From Baseline through Week 56

Results posted on

2025-07-11

Participant Flow

Participant milestones

Participant milestones
Measure	A: Faricimab 6 mg Q8W Participants randomized to Arm A received 6 milligrams (mg) faricimab intravitreal (IVT) injections once every 4 weeks (Q4W) to Week 20, followed by 6 mg faricimab IVT injections once every 8 weeks (Q8W) to Week 96, followed by the final study visit at Week 100.	B: Faricimab 6 mg PTI Participants randomized to Arm B received 6 milligrams (mg) faricimab intravitreal (IVT) injections Q4W to at least Week 12, followed by a personalized treatment interval (PTI) dosing of 6 mg faricimab IVT injections up to once every 16 weeks (Q16W) through Week 96, followed by the final study visit at Week 100.	C: Aflibercept 2 mg Q8W Participants randomized to Arm C received 2 milligrams (mg) aflibercept intravitreal (IVT) injections Q4W to Week 16, followed by 2 mg aflibercept IVT injections Q8W to Week 96, followed by the final study visit at Week 100.
Overall Study STARTED	315	313	312
Overall Study Received at Least One Dose of Study Drug	313	313	311
Overall Study Completed up to Week 56	291	289	292
Overall Study COMPLETED	263	269	260
Overall Study NOT COMPLETED	52	44	52

Reasons for withdrawal

Reasons for withdrawal
Measure	A: Faricimab 6 mg Q8W Participants randomized to Arm A received 6 milligrams (mg) faricimab intravitreal (IVT) injections once every 4 weeks (Q4W) to Week 20, followed by 6 mg faricimab IVT injections once every 8 weeks (Q8W) to Week 96, followed by the final study visit at Week 100.	B: Faricimab 6 mg PTI Participants randomized to Arm B received 6 milligrams (mg) faricimab intravitreal (IVT) injections Q4W to at least Week 12, followed by a personalized treatment interval (PTI) dosing of 6 mg faricimab IVT injections up to once every 16 weeks (Q16W) through Week 96, followed by the final study visit at Week 100.	C: Aflibercept 2 mg Q8W Participants randomized to Arm C received 2 milligrams (mg) aflibercept intravitreal (IVT) injections Q4W to Week 16, followed by 2 mg aflibercept IVT injections Q8W to Week 96, followed by the final study visit at Week 100.
Overall Study Death	16	21	13
Overall Study Adverse Event	6	6	5
Overall Study Withdrawal by Subject	12	7	19
Overall Study Lost to Follow-up	12	9	9
Overall Study Protocol Violation	1	0	1
Overall Study Physician Decision	3	0	1
Overall Study Pregnancy	0	1	0
Overall Study Lack of Efficacy	0	0	1
Overall Study Other	2	0	3

Baseline Characteristics

The ITT and Treatment-Naive (TN) Populations are grouped according to treatment assigned at randomization. The ITT Population (940) includes all global participants randomized in the study. The TN Population (725), a subset of ITT, includes randomized participants who had not received any IVT anti-VEGF agents in the study eye before randomization.

Baseline characteristics by cohort

PRIMARY outcome

Timeframe: From Baseline through Week 56

Population: ITT Population and Treatment-Naive Population

Outcome measures

Outcome measures
Measure	A: Faricimab 6 mg Q8W n=315 Participants Participants randomized to Arm A received 6 milligrams (mg) faricimab intravitreal (IVT) injections once every 4 weeks (Q4W) to Week 20, followed by 6 mg faricimab IVT injections once every 8 weeks (Q8W) to Week 96, followed by the final study visit at Week 100.	B: Faricimab 6 mg PTI n=313 Participants Participants randomized to Arm B received 6 milligrams (mg) faricimab intravitreal (IVT) injections Q4W to at least Week 12, followed by a personalized treatment interval (PTI) dosing of 6 mg faricimab IVT injections up to once every 16 weeks (Q16W) through Week 96, followed by the final study visit at Week 100.	C: Aflibercept 2 mg Q8W n=312 Participants Participants randomized to Arm C received 2 milligrams (mg) aflibercept intravitreal (IVT) injections Q4W to Week 16, followed by 2 mg aflibercept IVT injections Q8W to Week 96, followed by the final study visit at Week 100.
Change From Baseline in BCVA in the Study Eye Averaged Over Weeks 48, 52, and 56, ITT and Treatment-Naive Populations ITT Population	10.7 ETDRS Letters Interval 9.4 to 12.0	11.6 ETDRS Letters Interval 10.3 to 12.9	10.9 ETDRS Letters Interval 9.6 to 12.2
Change From Baseline in BCVA in the Study Eye Averaged Over Weeks 48, 52, and 56, ITT and Treatment-Naive Populations Treatment-Naive Population	10.6 ETDRS Letters Interval 9.1 to 12.1	11.4 ETDRS Letters Interval 9.9 to 12.8	11.3 ETDRS Letters Interval 9.8 to 12.8

SECONDARY outcome

Timeframe: Baseline and Week 52

Population: ITT Population and Treatment-Naive Population. Only participants with non-missing, valid assessments at Baseline and Week 52 were included in the analysis.

The Early Treatment Diabetic Retinopathy Study (ETDRS) Diabetic Retinopathy Severity Scale (DRSS) classifies diabetic retinopathy into 12 severity steps ranging from absence of retinopathy to advanced proliferative diabetic retinopathy. Ocular imaging assessments were made independently by a central reading center. The weighted estimates of the percentage of participants were based on the Cochran-Mantel Haenszel (CMH) weights stratified by baseline BCVA (≥64 vs. \<64 letters), prior IVT anti-VEGF therapy (yes vs. no), and region (U.S. and Canada vs. rest of the world; Asia and rest of the world regions were combined). Treatment policy strategy (i.e., all observed values used) and hypothetical strategy (i.e., all values censored after the occurrence of the intercurrent event) were applied to non-COVID-19 related and COVID-19 related intercurrent events, respectively. Missing data were not imputed. 97.5% confidence interval (CI) is a rounding of 97.52% CI.

Outcome measures

Outcome measures
Measure	A: Faricimab 6 mg Q8W n=237 Participants Participants randomized to Arm A received 6 milligrams (mg) faricimab intravitreal (IVT) injections once every 4 weeks (Q4W) to Week 20, followed by 6 mg faricimab IVT injections once every 8 weeks (Q8W) to Week 96, followed by the final study visit at Week 100.	B: Faricimab 6 mg PTI n=242 Participants Participants randomized to Arm B received 6 milligrams (mg) faricimab intravitreal (IVT) injections Q4W to at least Week 12, followed by a personalized treatment interval (PTI) dosing of 6 mg faricimab IVT injections up to once every 16 weeks (Q16W) through Week 96, followed by the final study visit at Week 100.	C: Aflibercept 2 mg Q8W n=229 Participants Participants randomized to Arm C received 2 milligrams (mg) aflibercept intravitreal (IVT) injections Q4W to Week 16, followed by 2 mg aflibercept IVT injections Q8W to Week 96, followed by the final study visit at Week 100.
Percentage of Participants With a ≥2-Step Diabetic Retinopathy Severity Improvement From Baseline on the ETDRS Diabetic Retinopathy Severity Scale at Week 52, ITT and Treatment-Naive Populations ITT Population	46.0 Percentage of participants Interval 38.8 to 53.1	42.5 Percentage of participants Interval 35.5 to 49.5	35.8 Percentage of participants Interval 29.1 to 42.5
Percentage of Participants With a ≥2-Step Diabetic Retinopathy Severity Improvement From Baseline on the ETDRS Diabetic Retinopathy Severity Scale at Week 52, ITT and Treatment-Naive Populations Treatment-Naive Population	49.7 Percentage of participants Interval 41.2 to 58.2	47.6 Percentage of participants Interval 39.5 to 55.8	42.5 Percentage of participants Interval 34.4 to 50.6

SECONDARY outcome

Timeframe: Baseline, Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, 56, 60, 64, 68, 72, 76, 80, 84, 88, 92, 96, and 100

Population: ITT Population: all participants who were randomized in the study, grouped according to the treatment assigned at randomization.

Outcome measures

Outcome measures
Measure	A: Faricimab 6 mg Q8W n=315 Participants Participants randomized to Arm A received 6 milligrams (mg) faricimab intravitreal (IVT) injections once every 4 weeks (Q4W) to Week 20, followed by 6 mg faricimab IVT injections once every 8 weeks (Q8W) to Week 96, followed by the final study visit at Week 100.	B: Faricimab 6 mg PTI n=313 Participants Participants randomized to Arm B received 6 milligrams (mg) faricimab intravitreal (IVT) injections Q4W to at least Week 12, followed by a personalized treatment interval (PTI) dosing of 6 mg faricimab IVT injections up to once every 16 weeks (Q16W) through Week 96, followed by the final study visit at Week 100.	C: Aflibercept 2 mg Q8W n=312 Participants Participants randomized to Arm C received 2 milligrams (mg) aflibercept intravitreal (IVT) injections Q4W to Week 16, followed by 2 mg aflibercept IVT injections Q8W to Week 96, followed by the final study visit at Week 100.
Change From Baseline in BCVA in the Study Eye Over Time, ITT Population Week 4	5.5 ETDRS Letters Interval 4.8 to 6.3	6.7 ETDRS Letters Interval 6.0 to 7.4	6.5 ETDRS Letters Interval 5.8 to 7.2
Change From Baseline in BCVA in the Study Eye Over Time, ITT Population Week 8	7.2 ETDRS Letters Interval 6.4 to 7.9	8.2 ETDRS Letters Interval 7.4 to 9.0	8.1 ETDRS Letters Interval 7.3 to 8.8
Change From Baseline in BCVA in the Study Eye Over Time, ITT Population Week 12	8.2 ETDRS Letters Interval 7.4 to 9.0	9.2 ETDRS Letters Interval 8.4 to 10.0	9.1 ETDRS Letters Interval 8.3 to 9.9
Change From Baseline in BCVA in the Study Eye Over Time, ITT Population Week 16	9.1 ETDRS Letters Interval 8.2 to 9.9	10.0 ETDRS Letters Interval 9.2 to 10.8	9.7 ETDRS Letters Interval 8.8 to 10.5
Change From Baseline in BCVA in the Study Eye Over Time, ITT Population Week 20	9.6 ETDRS Letters Interval 8.7 to 10.5	9.9 ETDRS Letters Interval 9.0 to 10.8	9.8 ETDRS Letters Interval 8.9 to 10.7
Change From Baseline in BCVA in the Study Eye Over Time, ITT Population Week 24	10.2 ETDRS Letters Interval 9.3 to 11.1	11.3 ETDRS Letters Interval 10.4 to 12.2	9.4 ETDRS Letters Interval 8.5 to 10.3
Change From Baseline in BCVA in the Study Eye Over Time, ITT Population Week 28	9.5 ETDRS Letters Interval 8.6 to 10.5	11.0 ETDRS Letters Interval 10.0 to 11.9	10.5 ETDRS Letters Interval 9.6 to 11.5
Change From Baseline in BCVA in the Study Eye Over Time, ITT Population Week 32	10.2 ETDRS Letters Interval 9.2 to 11.2	10.9 ETDRS Letters Interval 9.9 to 11.9	10.2 ETDRS Letters Interval 9.2 to 11.2
Change From Baseline in BCVA in the Study Eye Over Time, ITT Population Week 36	10.1 ETDRS Letters Interval 9.1 to 11.1	11.7 ETDRS Letters Interval 10.7 to 12.8	10.4 ETDRS Letters Interval 9.4 to 11.4
Change From Baseline in BCVA in the Study Eye Over Time, ITT Population Week 40	10.2 ETDRS Letters Interval 9.1 to 11.2	11.4 ETDRS Letters Interval 10.3 to 12.5	10.3 ETDRS Letters Interval 9.2 to 11.4
Change From Baseline in BCVA in the Study Eye Over Time, ITT Population Week 44	9.9 ETDRS Letters Interval 8.8 to 11.0	11.4 ETDRS Letters Interval 10.3 to 12.5	10.7 ETDRS Letters Interval 9.6 to 11.9
Change From Baseline in BCVA in the Study Eye Over Time, ITT Population Week 48	10.5 ETDRS Letters Interval 9.4 to 11.6	11.4 ETDRS Letters Interval 10.3 to 12.5	10.8 ETDRS Letters Interval 9.7 to 11.9
Change From Baseline in BCVA in the Study Eye Over Time, ITT Population Week 52	9.9 ETDRS Letters Interval 8.7 to 11.1	11.0 ETDRS Letters Interval 9.8 to 12.2	10.9 ETDRS Letters Interval 9.7 to 12.2
Change From Baseline in BCVA in the Study Eye Over Time, ITT Population Week 56	10.8 ETDRS Letters Interval 9.7 to 12.0	11.6 ETDRS Letters Interval 10.4 to 12.8	10.6 ETDRS Letters Interval 9.4 to 11.8
Change From Baseline in BCVA in the Study Eye Over Time, ITT Population Week 60	10.3 ETDRS Letters Interval 9.1 to 11.5	12.0 ETDRS Letters Interval 10.8 to 13.1	11.3 ETDRS Letters Interval 10.1 to 12.5
Change From Baseline in BCVA in the Study Eye Over Time, ITT Population Week 64	10.7 ETDRS Letters Interval 9.5 to 12.0	11.5 ETDRS Letters Interval 10.3 to 12.7	10.8 ETDRS Letters Interval 9.6 to 12.0
Change From Baseline in BCVA in the Study Eye Over Time, ITT Population Week 68	10.2 ETDRS Letters Interval 8.9 to 11.5	11.4 ETDRS Letters Interval 10.1 to 12.6	11.3 ETDRS Letters Interval 10.0 to 12.5
Change From Baseline in BCVA in the Study Eye Over Time, ITT Population Week 72	10.4 ETDRS Letters Interval 9.1 to 11.7	11.3 ETDRS Letters Interval 10.0 to 12.6	10.7 ETDRS Letters Interval 9.4 to 12.0
Change From Baseline in BCVA in the Study Eye Over Time, ITT Population Week 76	10.2 ETDRS Letters Interval 8.8 to 11.6	11.5 ETDRS Letters Interval 10.1 to 12.9	11.0 ETDRS Letters Interval 9.6 to 12.4
Change From Baseline in BCVA in the Study Eye Over Time, ITT Population Week 80	10.9 ETDRS Letters Interval 9.5 to 12.2	11.1 ETDRS Letters Interval 9.8 to 12.4	10.9 ETDRS Letters Interval 9.6 to 12.2
Change From Baseline in BCVA in the Study Eye Over Time, ITT Population Week 84	9.9 ETDRS Letters Interval 8.6 to 11.2	11.5 ETDRS Letters Interval 10.2 to 12.8	11.8 ETDRS Letters Interval 10.5 to 13.1
Change From Baseline in BCVA in the Study Eye Over Time, ITT Population Week 88	9.8 ETDRS Letters Interval 8.4 to 11.2	10.9 ETDRS Letters Interval 9.5 to 12.3	11.0 ETDRS Letters Interval 9.6 to 12.4
Change From Baseline in BCVA in the Study Eye Over Time, ITT Population Week 92	10.5 ETDRS Letters Interval 9.1 to 11.9	11.2 ETDRS Letters Interval 9.9 to 12.6	11.5 ETDRS Letters Interval 10.1 to 12.9
Change From Baseline in BCVA in the Study Eye Over Time, ITT Population Week 96	11.1 ETDRS Letters Interval 9.7 to 12.6	10.6 ETDRS Letters Interval 9.2 to 12.0	11.1 ETDRS Letters Interval 9.7 to 12.5
Change From Baseline in BCVA in the Study Eye Over Time, ITT Population Week 100	10.5 ETDRS Letters Interval 9.1 to 12.0	10.4 ETDRS Letters Interval 9.0 to 11.8	11.6 ETDRS Letters Interval 10.1 to 13.1

SECONDARY outcome

Timeframe: Baseline, Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, 56, 60, 64, 68, 72, 76, 80, 84, 88, 92, 96, and 100

Best-Corrected Visual Acuity (BCVA) was measured on the Early Treatment Diabetic Retinopathy Study (ETDRS) chart at a starting distance of 4 meters. The BCVA letter score ranges from 0 to 100 (best score attainable), and a gain in BCVA letter score from baseline indicates an improvement in visual acuity. For the Mixed Model for Repeated Measures (MMRM) analysis, the model adjusted for treatment group, visit, visit-by-treatment group interaction, baseline BCVA (continuous), baseline BCVA (\<64 vs. ≥64 letters), and region of enrollment. An unstructured covariance structure was used. Treatment policy strategy (i.e., all observed values used) and hypothetical strategy (i.e., all values censored after the occurrence of the intercurrent event) were applied to non-COVID-19 related and COVID-19 related intercurrent events, respectively. Missing data were implicitly imputed by MMRM. Invalid BCVA values were excluded from analysis. 95% confidence interval (CI) is a rounding of 95.04% CI.

Outcome measures

Outcome measures
Measure	A: Faricimab 6 mg Q8W n=238 Participants Participants randomized to Arm A received 6 milligrams (mg) faricimab intravitreal (IVT) injections once every 4 weeks (Q4W) to Week 20, followed by 6 mg faricimab IVT injections once every 8 weeks (Q8W) to Week 96, followed by the final study visit at Week 100.	B: Faricimab 6 mg PTI n=245 Participants Participants randomized to Arm B received 6 milligrams (mg) faricimab intravitreal (IVT) injections Q4W to at least Week 12, followed by a personalized treatment interval (PTI) dosing of 6 mg faricimab IVT injections up to once every 16 weeks (Q16W) through Week 96, followed by the final study visit at Week 100.	C: Aflibercept 2 mg Q8W n=242 Participants Participants randomized to Arm C received 2 milligrams (mg) aflibercept intravitreal (IVT) injections Q4W to Week 16, followed by 2 mg aflibercept IVT injections Q8W to Week 96, followed by the final study visit at Week 100.
Change From Baseline in BCVA in the Study Eye Over Time, Treatment-Naive Population Week 4	5.8 ETDRS Letters Interval 5.0 to 6.7	6.8 ETDRS Letters Interval 6.0 to 7.6	6.9 ETDRS Letters Interval 6.1 to 7.7
Change From Baseline in BCVA in the Study Eye Over Time, Treatment-Naive Population Week 8	7.2 ETDRS Letters Interval 6.3 to 8.1	8.3 ETDRS Letters Interval 7.4 to 9.2	8.7 ETDRS Letters Interval 7.8 to 9.5
Change From Baseline in BCVA in the Study Eye Over Time, Treatment-Naive Population Week 12	8.5 ETDRS Letters Interval 7.6 to 9.4	9.3 ETDRS Letters Interval 8.4 to 10.2	9.6 ETDRS Letters Interval 8.7 to 10.5
Change From Baseline in BCVA in the Study Eye Over Time, Treatment-Naive Population Week 16	9.3 ETDRS Letters Interval 8.4 to 10.3	10.0 ETDRS Letters Interval 9.1 to 10.9	10.1 ETDRS Letters Interval 9.2 to 11.1
Change From Baseline in BCVA in the Study Eye Over Time, Treatment-Naive Population Week 20	9.7 ETDRS Letters Interval 8.7 to 10.8	9.7 ETDRS Letters Interval 8.6 to 10.7	10.3 ETDRS Letters Interval 9.3 to 11.4
Change From Baseline in BCVA in the Study Eye Over Time, Treatment-Naive Population Week 24	10.5 ETDRS Letters Interval 9.4 to 11.5	11.2 ETDRS Letters Interval 10.2 to 12.2	9.8 ETDRS Letters Interval 8.7 to 10.8
Change From Baseline in BCVA in the Study Eye Over Time, Treatment-Naive Population Week 28	9.6 ETDRS Letters Interval 8.5 to 10.7	11.0 ETDRS Letters Interval 9.9 to 12.1	11.0 ETDRS Letters Interval 9.9 to 12.1
Change From Baseline in BCVA in the Study Eye Over Time, Treatment-Naive Population Week 32	10.3 ETDRS Letters Interval 9.1 to 11.5	10.9 ETDRS Letters Interval 9.8 to 12.1	10.6 ETDRS Letters Interval 9.5 to 11.8
Change From Baseline in BCVA in the Study Eye Over Time, Treatment-Naive Population Week 36	10.3 ETDRS Letters Interval 9.1 to 11.6	11.9 ETDRS Letters Interval 10.7 to 13.1	10.6 ETDRS Letters Interval 9.4 to 11.8
Change From Baseline in BCVA in the Study Eye Over Time, Treatment-Naive Population Week 40	10.0 ETDRS Letters Interval 8.7 to 11.3	11.4 ETDRS Letters Interval 10.1 to 12.7	10.7 ETDRS Letters Interval 9.4 to 12.1
Change From Baseline in BCVA in the Study Eye Over Time, Treatment-Naive Population Week 44	10.1 ETDRS Letters Interval 8.8 to 11.4	11.4 ETDRS Letters Interval 10.1 to 12.7	11.3 ETDRS Letters Interval 10.0 to 12.6
Change From Baseline in BCVA in the Study Eye Over Time, Treatment-Naive Population Week 48	10.3 ETDRS Letters Interval 9.0 to 11.7	11.0 ETDRS Letters Interval 9.7 to 12.4	11.2 ETDRS Letters Interval 9.8 to 12.5
Change From Baseline in BCVA in the Study Eye Over Time, Treatment-Naive Population Week 52	9.6 ETDRS Letters Interval 8.2 to 11.1	10.7 ETDRS Letters Interval 9.3 to 12.2	11.3 ETDRS Letters Interval 9.9 to 12.8
Change From Baseline in BCVA in the Study Eye Over Time, Treatment-Naive Population Week 56	10.9 ETDRS Letters Interval 9.5 to 12.3	11.5 ETDRS Letters Interval 10.1 to 12.8	11.0 ETDRS Letters Interval 9.6 to 12.4
Change From Baseline in BCVA in the Study Eye Over Time, Treatment-Naive Population Week 60	10.1 ETDRS Letters Interval 8.7 to 11.6	12.0 ETDRS Letters Interval 10.6 to 13.4	11.6 ETDRS Letters Interval 10.2 to 13.0
Change From Baseline in BCVA in the Study Eye Over Time, Treatment-Naive Population Week 64	10.6 ETDRS Letters Interval 9.1 to 12.1	11.5 ETDRS Letters Interval 10.0 to 13.0	11.0 ETDRS Letters Interval 9.5 to 12.4
Change From Baseline in BCVA in the Study Eye Over Time, Treatment-Naive Population Week 68	10.3 ETDRS Letters Interval 8.8 to 11.8	11.3 ETDRS Letters Interval 9.8 to 12.8	11.4 ETDRS Letters Interval 9.9 to 12.9
Change From Baseline in BCVA in the Study Eye Over Time, Treatment-Naive Population Week 72	10.2 ETDRS Letters Interval 8.6 to 11.7	11.3 ETDRS Letters Interval 9.8 to 12.8	10.8 ETDRS Letters Interval 9.3 to 12.4
Change From Baseline in BCVA in the Study Eye Over Time, Treatment-Naive Population Week 76	9.9 ETDRS Letters Interval 8.2 to 11.6	11.4 ETDRS Letters Interval 9.7 to 13.0	10.8 ETDRS Letters Interval 9.2 to 12.5
Change From Baseline in BCVA in the Study Eye Over Time, Treatment-Naive Population Week 80	10.6 ETDRS Letters Interval 9.0 to 12.2	11.0 ETDRS Letters Interval 9.4 to 12.6	11.1 ETDRS Letters Interval 9.6 to 12.7
Change From Baseline in BCVA in the Study Eye Over Time, Treatment-Naive Population Week 84	9.6 ETDRS Letters Interval 8.0 to 11.1	11.6 ETDRS Letters Interval 10.0 to 13.1	11.9 ETDRS Letters Interval 10.3 to 13.4
Change From Baseline in BCVA in the Study Eye Over Time, Treatment-Naive Population Week 88	9.4 ETDRS Letters Interval 7.7 to 11.1	10.8 ETDRS Letters Interval 9.1 to 12.5	10.9 ETDRS Letters Interval 9.2 to 12.6
Change From Baseline in BCVA in the Study Eye Over Time, Treatment-Naive Population Week 92	10.1 ETDRS Letters Interval 8.4 to 11.7	11.2 ETDRS Letters Interval 9.5 to 12.8	11.6 ETDRS Letters Interval 10.0 to 13.3
Change From Baseline in BCVA in the Study Eye Over Time, Treatment-Naive Population Week 96	11.1 ETDRS Letters Interval 9.4 to 12.8	10.5 ETDRS Letters Interval 8.9 to 12.1	11.4 ETDRS Letters Interval 9.7 to 13.0
Change From Baseline in BCVA in the Study Eye Over Time, Treatment-Naive Population Week 100	10.5 ETDRS Letters Interval 8.8 to 12.3	10.5 ETDRS Letters Interval 8.8 to 12.1	11.7 ETDRS Letters Interval 10.0 to 13.4

SECONDARY outcome

Timeframe: Baseline, average of Weeks 48, 52, and 56

Population: ITT Population: all participants who were randomized in the study, grouped according to the treatment assigned at randomization. Only participants with at least one non-missing, valid assessment at Weeks 48, 52, or 56 were included in the analysis.

BCVA was measured on the ETDRS chart at a starting distance of 4 meters. The BCVA letter score ranges from 0 to 100 (best score), and a gain in BCVA from baseline indicates an improvement in visual acuity. For each participant, an average BCVA value was calculated across the three visits, and this averaged value was then used to determine if the endpoint was met. The results were summarized as the percentage of participants per treatment arm who met the endpoint. The weighted estimates of the percentage of participants were based on the Cochran-Mantel Haenszel (CMH) weights stratified by baseline BCVA (≥64 vs. \<64 letters), prior IVT anti-VEGF therapy (yes vs. no), and region (U.S. and Canada vs. rest of the world). Treatment policy strategy and hypothetical strategy were applied to non-COVID-19 related and COVID-19 related intercurrent events, respectively. Missing data were not imputed. Invalid BCVA values were excluded. 95% confidence interval (CI) is a rounding of 95.04% CI.

Outcome measures

Outcome measures
Measure	A: Faricimab 6 mg Q8W n=271 Participants Participants randomized to Arm A received 6 milligrams (mg) faricimab intravitreal (IVT) injections once every 4 weeks (Q4W) to Week 20, followed by 6 mg faricimab IVT injections once every 8 weeks (Q8W) to Week 96, followed by the final study visit at Week 100.	B: Faricimab 6 mg PTI n=276 Participants Participants randomized to Arm B received 6 milligrams (mg) faricimab intravitreal (IVT) injections Q4W to at least Week 12, followed by a personalized treatment interval (PTI) dosing of 6 mg faricimab IVT injections up to once every 16 weeks (Q16W) through Week 96, followed by the final study visit at Week 100.	C: Aflibercept 2 mg Q8W n=276 Participants Participants randomized to Arm C received 2 milligrams (mg) aflibercept intravitreal (IVT) injections Q4W to Week 16, followed by 2 mg aflibercept IVT injections Q8W to Week 96, followed by the final study visit at Week 100.
Percentage of Participants Gaining Greater Than or Equal to (≥)15, ≥10, ≥5, or ≥0 Letters in BCVA From Baseline in the Study Eye Averaged Over Weeks 48, 52, and 56, ITT Population Gaining ≥15 Letters	29.2 Percentage of participants Interval 23.9 to 34.5	35.5 Percentage of participants Interval 30.1 to 40.9	31.8 Percentage of participants Interval 26.6 to 37.0
Percentage of Participants Gaining Greater Than or Equal to (≥)15, ≥10, ≥5, or ≥0 Letters in BCVA From Baseline in the Study Eye Averaged Over Weeks 48, 52, and 56, ITT Population Gaining ≥10 Letters	57.2 Percentage of participants Interval 51.3 to 63.1	58.3 Percentage of participants Interval 52.6 to 64.0	57.6 Percentage of participants Interval 51.8 to 63.4
Percentage of Participants Gaining Greater Than or Equal to (≥)15, ≥10, ≥5, or ≥0 Letters in BCVA From Baseline in the Study Eye Averaged Over Weeks 48, 52, and 56, ITT Population Gaining ≥5 Letters	78.9 Percentage of participants Interval 74.1 to 83.8	79.6 Percentage of participants Interval 74.9 to 84.3	81.4 Percentage of participants Interval 76.9 to 86.0
Percentage of Participants Gaining Greater Than or Equal to (≥)15, ≥10, ≥5, or ≥0 Letters in BCVA From Baseline in the Study Eye Averaged Over Weeks 48, 52, and 56, ITT Population Gaining ≥0 Letters	91.5 Percentage of participants Interval 88.1 to 94.8	94.5 Percentage of participants Interval 91.8 to 97.2	91.4 Percentage of participants Interval 88.1 to 94.6

SECONDARY outcome

Timeframe: Baseline, Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, 56, 60, 64, 68, 72, 76, 80, 84, 88, 92, 96, and 100

Population: ITT Population: all participants who were randomized in the study, grouped according to the treatment assigned at randomization. At each timepoint, only participants with non-missing, valid assessments were included in the analysis.

Best Corrected Visual Acuity (BCVA) was measured on the Early Treatment Diabetic Retinopathy Study (ETDRS) chart at a starting distance of 4 meters. The BCVA letter score ranges from 0 to 100 (best score), and a gain in BCVA letter score from baseline indicates an improvement in visual acuity. The weighted estimates of the percentage of participants were based on the Cochran-Mantel Haenszel (CMH) weights stratified by baseline BCVA (≥64 vs. \<64 letters), prior IVT anti-VEGF therapy (yes vs. no), and region (U.S. and Canada vs. rest of the world; Asia and rest of the world were combined). Treatment policy strategy (i.e., all observed values used) and hypothetical strategy (i.e., all values censored after the occurrence of the intercurrent event) were applied to non-COVID-19 related and COVID-19 related intercurrent events, respectively. Missing data were not imputed. Invalid BCVA values were excluded from analysis. 95% confidence interval (CI) is a rounding of 95.04% CI.

Outcome measures

Outcome measures
Measure	A: Faricimab 6 mg Q8W n=315 Participants Participants randomized to Arm A received 6 milligrams (mg) faricimab intravitreal (IVT) injections once every 4 weeks (Q4W) to Week 20, followed by 6 mg faricimab IVT injections once every 8 weeks (Q8W) to Week 96, followed by the final study visit at Week 100.	B: Faricimab 6 mg PTI n=313 Participants Participants randomized to Arm B received 6 milligrams (mg) faricimab intravitreal (IVT) injections Q4W to at least Week 12, followed by a personalized treatment interval (PTI) dosing of 6 mg faricimab IVT injections up to once every 16 weeks (Q16W) through Week 96, followed by the final study visit at Week 100.	C: Aflibercept 2 mg Q8W n=312 Participants Participants randomized to Arm C received 2 milligrams (mg) aflibercept intravitreal (IVT) injections Q4W to Week 16, followed by 2 mg aflibercept IVT injections Q8W to Week 96, followed by the final study visit at Week 100.
Percentage of Participants Gaining ≥15 Letters in BCVA From Baseline in the Study Eye Over Time, ITT Population Week 4	7.7 Percentage of participants Interval 4.8 to 10.7	13.0 Percentage of participants Interval 9.4 to 16.6	11.4 Percentage of participants Interval 8.0 to 14.9
Percentage of Participants Gaining ≥15 Letters in BCVA From Baseline in the Study Eye Over Time, ITT Population Week 8	13.4 Percentage of participants Interval 9.6 to 17.1	18.8 Percentage of participants Interval 14.8 to 22.9	16.7 Percentage of participants Interval 12.7 to 20.7
Percentage of Participants Gaining ≥15 Letters in BCVA From Baseline in the Study Eye Over Time, ITT Population Week 12	14.9 Percentage of participants Interval 11.0 to 18.9	23.1 Percentage of participants Interval 18.6 to 27.5	22.1 Percentage of participants Interval 17.6 to 26.5
Percentage of Participants Gaining ≥15 Letters in BCVA From Baseline in the Study Eye Over Time, ITT Population Week 16	20.4 Percentage of participants Interval 15.9 to 24.9	27.8 Percentage of participants Interval 22.9 to 32.7	22.2 Percentage of participants Interval 17.7 to 26.8
Percentage of Participants Gaining ≥15 Letters in BCVA From Baseline in the Study Eye Over Time, ITT Population Week 20	25.6 Percentage of participants Interval 20.8 to 30.5	28.4 Percentage of participants Interval 23.4 to 33.4	24.0 Percentage of participants Interval 19.4 to 28.6
Percentage of Participants Gaining ≥15 Letters in BCVA From Baseline in the Study Eye Over Time, ITT Population Week 24	26.8 Percentage of participants Interval 21.8 to 31.8	34.2 Percentage of participants Interval 29.0 to 39.3	25.7 Percentage of participants Interval 21.0 to 30.5
Percentage of Participants Gaining ≥15 Letters in BCVA From Baseline in the Study Eye Over Time, ITT Population Week 28	23.5 Percentage of participants Interval 18.6 to 28.4	31.2 Percentage of participants Interval 26.2 to 36.3	29.2 Percentage of participants Interval 24.3 to 34.2
Percentage of Participants Gaining ≥15 Letters in BCVA From Baseline in the Study Eye Over Time, ITT Population Week 32	28.5 Percentage of participants Interval 23.1 to 33.8	36.2 Percentage of participants Interval 30.7 to 41.7	25.8 Percentage of participants Interval 21.0 to 30.7
Percentage of Participants Gaining ≥15 Letters in BCVA From Baseline in the Study Eye Over Time, ITT Population Week 36	24.4 Percentage of participants Interval 19.3 to 29.5	40.2 Percentage of participants Interval 34.6 to 45.8	32.5 Percentage of participants Interval 27.1 to 37.9
Percentage of Participants Gaining ≥15 Letters in BCVA From Baseline in the Study Eye Over Time, ITT Population Week 40	29.7 Percentage of participants Interval 24.3 to 35.1	37.1 Percentage of participants Interval 31.6 to 42.7	30.3 Percentage of participants Interval 24.9 to 35.6
Percentage of Participants Gaining ≥15 Letters in BCVA From Baseline in the Study Eye Over Time, ITT Population Week 44	29.2 Percentage of participants Interval 23.8 to 34.6	37.1 Percentage of participants Interval 31.7 to 42.6	34.9 Percentage of participants Interval 29.4 to 40.4
Percentage of Participants Gaining ≥15 Letters in BCVA From Baseline in the Study Eye Over Time, ITT Population Week 48	31.7 Percentage of participants Interval 26.1 to 37.2	39.6 Percentage of participants Interval 33.9 to 45.3	34.0 Percentage of participants Interval 28.7 to 39.3
Percentage of Participants Gaining ≥15 Letters in BCVA From Baseline in the Study Eye Over Time, ITT Population Week 52	31.2 Percentage of participants Interval 25.7 to 36.8	37.2 Percentage of participants Interval 31.7 to 42.7	36.0 Percentage of participants Interval 30.3 to 41.6
Percentage of Participants Gaining ≥15 Letters in BCVA From Baseline in the Study Eye Over Time, ITT Population Week 56	38.1 Percentage of participants Interval 32.3 to 43.9	38.4 Percentage of participants Interval 32.7 to 44.0	31.5 Percentage of participants Interval 26.1 to 36.9
Percentage of Participants Gaining ≥15 Letters in BCVA From Baseline in the Study Eye Over Time, ITT Population Week 60	34.4 Percentage of participants Interval 28.8 to 40.0	41.3 Percentage of participants Interval 35.5 to 47.1	35.9 Percentage of participants Interval 30.3 to 41.4
Percentage of Participants Gaining ≥15 Letters in BCVA From Baseline in the Study Eye Over Time, ITT Population Week 64	37.5 Percentage of participants Interval 31.7 to 43.4	41.4 Percentage of participants Interval 35.8 to 47.1	34.8 Percentage of participants Interval 29.1 to 40.5
Percentage of Participants Gaining ≥15 Letters in BCVA From Baseline in the Study Eye Over Time, ITT Population Week 68	37.1 Percentage of participants Interval 31.4 to 42.9	43.7 Percentage of participants Interval 37.9 to 49.6	37.1 Percentage of participants Interval 31.4 to 42.8
Percentage of Participants Gaining ≥15 Letters in BCVA From Baseline in the Study Eye Over Time, ITT Population Week 72	34.8 Percentage of participants Interval 29.1 to 40.6	38.2 Percentage of participants Interval 32.6 to 43.8	35.2 Percentage of participants Interval 29.5 to 41.0
Percentage of Participants Gaining ≥15 Letters in BCVA From Baseline in the Study Eye Over Time, ITT Population Week 76	36.6 Percentage of participants Interval 30.7 to 42.6	44.1 Percentage of participants Interval 38.4 to 49.9	37.2 Percentage of participants Interval 31.3 to 43.1
Percentage of Participants Gaining ≥15 Letters in BCVA From Baseline in the Study Eye Over Time, ITT Population Week 80	39.3 Percentage of participants Interval 33.4 to 45.3	42.1 Percentage of participants Interval 36.5 to 47.8	36.9 Percentage of participants Interval 31.1 to 42.6
Percentage of Participants Gaining ≥15 Letters in BCVA From Baseline in the Study Eye Over Time, ITT Population Week 84	40.6 Percentage of participants Interval 34.5 to 46.6	41.5 Percentage of participants Interval 35.8 to 47.2	38.8 Percentage of participants Interval 32.9 to 44.6
Percentage of Participants Gaining ≥15 Letters in BCVA From Baseline in the Study Eye Over Time, ITT Population Week 88	39.2 Percentage of participants Interval 33.2 to 45.2	39.8 Percentage of participants Interval 34.2 to 45.4	35.9 Percentage of participants Interval 30.1 to 41.6
Percentage of Participants Gaining ≥15 Letters in BCVA From Baseline in the Study Eye Over Time, ITT Population Week 92	39.7 Percentage of participants Interval 33.8 to 45.7	41.0 Percentage of participants Interval 35.3 to 46.6	38.8 Percentage of participants Interval 33.0 to 44.7
Percentage of Participants Gaining ≥15 Letters in BCVA From Baseline in the Study Eye Over Time, ITT Population Week 96	41.3 Percentage of participants Interval 35.1 to 47.4	40.2 Percentage of participants Interval 34.5 to 45.8	38.8 Percentage of participants Interval 32.9 to 44.7
Percentage of Participants Gaining ≥15 Letters in BCVA From Baseline in the Study Eye Over Time, ITT Population Week 100	40.2 Percentage of participants Interval 34.2 to 46.1	40.3 Percentage of participants Interval 34.7 to 46.0	40.9 Percentage of participants Interval 34.9 to 46.9

SECONDARY outcome

Timeframe: Baseline, Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, 56, 60, 64, 68, 72, 76, 80, 84, 88, 92, 96, and 100

Best Corrected Visual Acuity (BCVA) was measured on the Early Treatment Diabetic Retinopathy Study (ETDRS) chart at a starting distance of 4 meters. The BCVA letter score ranges from 0 to 100 (best score), and a gain in BCVA letter score from baseline indicates an improvement in visual acuity. The weighted estimates of the percentage of participants were based on the Cochran-Mantel Haenszel (CMH) weights stratified by baseline BCVA (≥64 vs. \<64 letters), prior IVT anti-VEGF therapy (yes vs. no), and region (U.S. and Canada vs. rest of the world; Asia and rest of the world were combined). Treatment policy strategy (i.e., all observed values used) and hypothetical strategy (i.e., all values censored after the occurrence of the intercurrent event) were applied to non-COVID-19 related and COVID-19 related intercurrent events, respectively. Missing data were not imputed. Invalid BCVA values were excluded from analysis. 95% confidence interval (CI) is a rounding of 95.04% CI.

Outcome measures

Outcome measures
Measure	A: Faricimab 6 mg Q8W n=315 Participants Participants randomized to Arm A received 6 milligrams (mg) faricimab intravitreal (IVT) injections once every 4 weeks (Q4W) to Week 20, followed by 6 mg faricimab IVT injections once every 8 weeks (Q8W) to Week 96, followed by the final study visit at Week 100.	B: Faricimab 6 mg PTI n=313 Participants Participants randomized to Arm B received 6 milligrams (mg) faricimab intravitreal (IVT) injections Q4W to at least Week 12, followed by a personalized treatment interval (PTI) dosing of 6 mg faricimab IVT injections up to once every 16 weeks (Q16W) through Week 96, followed by the final study visit at Week 100.	C: Aflibercept 2 mg Q8W n=312 Participants Participants randomized to Arm C received 2 milligrams (mg) aflibercept intravitreal (IVT) injections Q4W to Week 16, followed by 2 mg aflibercept IVT injections Q8W to Week 96, followed by the final study visit at Week 100.
Percentage of Participants Gaining ≥10 Letters in BCVA From Baseline in the Study Eye Over Time, ITT Population Week 16	43.7 Percentage of participants Interval 38.0 to 49.3	48.4 Percentage of participants Interval 42.8 to 54.0	49.7 Percentage of participants Interval 44.1 to 55.3
Percentage of Participants Gaining ≥10 Letters in BCVA From Baseline in the Study Eye Over Time, ITT Population Week 4	23.9 Percentage of participants Interval 19.2 to 28.6	31.1 Percentage of participants Interval 26.2 to 36.1	27.1 Percentage of participants Interval 22.2 to 32.0
Percentage of Participants Gaining ≥10 Letters in BCVA From Baseline in the Study Eye Over Time, ITT Population Week 8	30.8 Percentage of participants Interval 25.7 to 35.9	37.1 Percentage of participants Interval 31.8 to 42.3	41.0 Percentage of participants Interval 35.6 to 46.4
Percentage of Participants Gaining ≥10 Letters in BCVA From Baseline in the Study Eye Over Time, ITT Population Week 12	35.5 Percentage of participants Interval 30.2 to 40.8	47.5 Percentage of participants Interval 42.0 to 53.0	46.2 Percentage of participants Interval 40.7 to 51.7
Percentage of Participants Gaining ≥10 Letters in BCVA From Baseline in the Study Eye Over Time, ITT Population Week 20	45.6 Percentage of participants Interval 40.0 to 51.3	53.1 Percentage of participants Interval 47.6 to 58.6	50.3 Percentage of participants Interval 44.7 to 56.0
Percentage of Participants Gaining ≥10 Letters in BCVA From Baseline in the Study Eye Over Time, ITT Population Week 24	55.6 Percentage of participants Interval 50.0 to 61.2	58.6 Percentage of participants Interval 53.2 to 64.1	48.2 Percentage of participants Interval 42.6 to 53.9
Percentage of Participants Gaining ≥10 Letters in BCVA From Baseline in the Study Eye Over Time, ITT Population Week 28	55.6 Percentage of participants Interval 49.9 to 61.3	57.0 Percentage of participants Interval 51.4 to 62.6	57.2 Percentage of participants Interval 51.6 to 62.9
Percentage of Participants Gaining ≥10 Letters in BCVA From Baseline in the Study Eye Over Time, ITT Population Week 32	56.7 Percentage of participants Interval 50.9 to 62.6	58.5 Percentage of participants Interval 52.8 to 64.2	53.1 Percentage of participants Interval 47.3 to 58.8
Percentage of Participants Gaining ≥10 Letters in BCVA From Baseline in the Study Eye Over Time, ITT Population Week 36	55.6 Percentage of participants Interval 49.7 to 61.5	65.5 Percentage of participants Interval 60.0 to 71.1	55.7 Percentage of participants Interval 49.9 to 61.6
Percentage of Participants Gaining ≥10 Letters in BCVA From Baseline in the Study Eye Over Time, ITT Population Week 40	55.7 Percentage of participants Interval 49.8 to 61.5	60.0 Percentage of participants Interval 54.2 to 65.8	53.2 Percentage of participants Interval 47.2 to 59.2
Percentage of Participants Gaining ≥10 Letters in BCVA From Baseline in the Study Eye Over Time, ITT Population Week 44	55.1 Percentage of participants Interval 49.3 to 61.0	60.5 Percentage of participants Interval 54.7 to 66.2	57.2 Percentage of participants Interval 51.3 to 63.2
Percentage of Participants Gaining ≥10 Letters in BCVA From Baseline in the Study Eye Over Time, ITT Population Week 48	57.0 Percentage of participants Interval 51.0 to 62.9	60.2 Percentage of participants Interval 54.5 to 65.9	61.7 Percentage of participants Interval 55.9 to 67.4
Percentage of Participants Gaining ≥10 Letters in BCVA From Baseline in the Study Eye Over Time, ITT Population Week 52	59.9 Percentage of participants Interval 54.0 to 65.8	59.5 Percentage of participants Interval 53.8 to 65.2	60.2 Percentage of participants Interval 54.3 to 66.2
Percentage of Participants Gaining ≥10 Letters in BCVA From Baseline in the Study Eye Over Time, ITT Population Week 56	63.5 Percentage of participants Interval 57.7 to 69.4	62.6 Percentage of participants Interval 56.9 to 68.3	59.0 Percentage of participants Interval 53.0 to 64.9
Percentage of Participants Gaining ≥10 Letters in BCVA From Baseline in the Study Eye Over Time, ITT Population Week 60	59.4 Percentage of participants Interval 53.5 to 65.2	62.6 Percentage of participants Interval 56.9 to 68.3	60.7 Percentage of participants Interval 54.9 to 66.5
Percentage of Participants Gaining ≥10 Letters in BCVA From Baseline in the Study Eye Over Time, ITT Population Week 64	64.9 Percentage of participants Interval 59.2 to 70.7	60.0 Percentage of participants Interval 54.3 to 65.7	59.6 Percentage of participants Interval 53.8 to 65.5
Percentage of Participants Gaining ≥10 Letters in BCVA From Baseline in the Study Eye Over Time, ITT Population Week 68	60.1 Percentage of participants Interval 54.2 to 66.0	58.9 Percentage of participants Interval 53.1 to 64.7	59.4 Percentage of participants Interval 53.5 to 65.4
Percentage of Participants Gaining ≥10 Letters in BCVA From Baseline in the Study Eye Over Time, ITT Population Week 72	61.2 Percentage of participants Interval 55.2 to 67.1	61.0 Percentage of participants Interval 55.2 to 66.8	56.8 Percentage of participants Interval 50.7 to 62.9
Percentage of Participants Gaining ≥10 Letters in BCVA From Baseline in the Study Eye Over Time, ITT Population Week 76	60.1 Percentage of participants Interval 54.1 to 66.2	67.8 Percentage of participants Interval 62.3 to 73.3	64.2 Percentage of participants Interval 58.3 to 70.0
Percentage of Participants Gaining ≥10 Letters in BCVA From Baseline in the Study Eye Over Time, ITT Population Week 80	64.0 Percentage of participants Interval 58.1 to 70.0	61.7 Percentage of participants Interval 56.1 to 67.4	60.5 Percentage of participants Interval 54.5 to 66.4
Percentage of Participants Gaining ≥10 Letters in BCVA From Baseline in the Study Eye Over Time, ITT Population Week 84	61.0 Percentage of participants Interval 55.0 to 67.0	64.4 Percentage of participants Interval 58.8 to 70.1	64.4 Percentage of participants Interval 58.6 to 70.2
Percentage of Participants Gaining ≥10 Letters in BCVA From Baseline in the Study Eye Over Time, ITT Population Week 88	59.6 Percentage of participants Interval 53.5 to 65.7	59.8 Percentage of participants Interval 54.0 to 65.7	62.7 Percentage of participants Interval 56.9 to 68.5
Percentage of Participants Gaining ≥10 Letters in BCVA From Baseline in the Study Eye Over Time, ITT Population Week 92	63.2 Percentage of participants Interval 57.3 to 69.1	63.3 Percentage of participants Interval 57.6 to 69.0	64.6 Percentage of participants Interval 58.7 to 70.4
Percentage of Participants Gaining ≥10 Letters in BCVA From Baseline in the Study Eye Over Time, ITT Population Week 96	60.3 Percentage of participants Interval 54.1 to 66.4	59.7 Percentage of participants Interval 53.9 to 65.5	62.5 Percentage of participants Interval 56.5 to 68.6
Percentage of Participants Gaining ≥10 Letters in BCVA From Baseline in the Study Eye Over Time, ITT Population Week 100	63.0 Percentage of participants Interval 57.3 to 68.8	60.5 Percentage of participants Interval 54.8 to 66.2	66.0 Percentage of participants Interval 60.1 to 71.8

SECONDARY outcome

Timeframe: Baseline, Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, 56, 60, 64, 68, 72, 76, 80, 84, 88, 92, 96, and 100

Best Corrected Visual Acuity (BCVA) was measured on the Early Treatment Diabetic Retinopathy Study (ETDRS) chart at a starting distance of 4 meters. The BCVA letter score ranges from 0 to 100 (best score), and a gain in BCVA letter score from baseline indicates an improvement in visual acuity. The weighted estimates of the percentage of participants were based on the Cochran-Mantel Haenszel (CMH) weights stratified by baseline BCVA (≥64 vs. \<64 letters), prior IVT anti-VEGF therapy (yes vs. no), and region (U.S. and Canada vs. rest of the world; Asia and rest of the world were combined). Treatment policy strategy (i.e., all observed values used) and hypothetical strategy (i.e., all values censored after the occurrence of the intercurrent event) were applied to non-COVID-19 related and COVID-19 related intercurrent events, respectively. Missing data were not imputed. Invalid BCVA values were excluded from analysis. 95% confidence interval (CI) is a rounding of 95.04% CI.

Outcome measures

Outcome measures
Measure	A: Faricimab 6 mg Q8W n=315 Participants Participants randomized to Arm A received 6 milligrams (mg) faricimab intravitreal (IVT) injections once every 4 weeks (Q4W) to Week 20, followed by 6 mg faricimab IVT injections once every 8 weeks (Q8W) to Week 96, followed by the final study visit at Week 100.	B: Faricimab 6 mg PTI n=313 Participants Participants randomized to Arm B received 6 milligrams (mg) faricimab intravitreal (IVT) injections Q4W to at least Week 12, followed by a personalized treatment interval (PTI) dosing of 6 mg faricimab IVT injections up to once every 16 weeks (Q16W) through Week 96, followed by the final study visit at Week 100.	C: Aflibercept 2 mg Q8W n=312 Participants Participants randomized to Arm C received 2 milligrams (mg) aflibercept intravitreal (IVT) injections Q4W to Week 16, followed by 2 mg aflibercept IVT injections Q8W to Week 96, followed by the final study visit at Week 100.
Percentage of Participants Gaining ≥5 Letters in BCVA From Baseline in the Study Eye Over Time, ITT Population Week 4	53.6 Percentage of participants Interval 48.1 to 59.1	62.6 Percentage of participants Interval 57.3 to 67.9	61.1 Percentage of participants Interval 55.7 to 66.5
Percentage of Participants Gaining ≥5 Letters in BCVA From Baseline in the Study Eye Over Time, ITT Population Week 8	64.7 Percentage of participants Interval 59.4 to 70.0	71.1 Percentage of participants Interval 66.1 to 76.0	67.6 Percentage of participants Interval 62.4 to 72.8
Percentage of Participants Gaining ≥5 Letters in BCVA From Baseline in the Study Eye Over Time, ITT Population Week 12	71.9 Percentage of participants Interval 66.9 to 76.9	74.3 Percentage of participants Interval 69.4 to 79.2	75.4 Percentage of participants Interval 70.6 to 80.3
Percentage of Participants Gaining ≥5 Letters in BCVA From Baseline in the Study Eye Over Time, ITT Population Week 16	74.9 Percentage of participants Interval 70.0 to 79.9	81.4 Percentage of participants Interval 77.0 to 85.8	77.5 Percentage of participants Interval 72.7 to 82.2
Percentage of Participants Gaining ≥5 Letters in BCVA From Baseline in the Study Eye Over Time, ITT Population Week 20	78.2 Percentage of participants Interval 73.6 to 82.9	78.4 Percentage of participants Interval 73.7 to 83.1	76.4 Percentage of participants Interval 71.6 to 81.1
Percentage of Participants Gaining ≥5 Letters in BCVA From Baseline in the Study Eye Over Time, ITT Population Week 24	80.5 Percentage of participants Interval 76.0 to 85.0	83.3 Percentage of participants Interval 79.0 to 87.5	71.0 Percentage of participants Interval 65.8 to 76.1
Percentage of Participants Gaining ≥5 Letters in BCVA From Baseline in the Study Eye Over Time, ITT Population Week 28	77.4 Percentage of participants Interval 72.5 to 82.2	81.0 Percentage of participants Interval 76.6 to 85.5	79.1 Percentage of participants Interval 74.4 to 83.8
Percentage of Participants Gaining ≥5 Letters in BCVA From Baseline in the Study Eye Over Time, ITT Population Week 32	79.4 Percentage of participants Interval 74.6 to 84.3	77.1 Percentage of participants Interval 72.2 to 82.0	81.3 Percentage of participants Interval 76.8 to 85.8
Percentage of Participants Gaining ≥5 Letters in BCVA From Baseline in the Study Eye Over Time, ITT Population Week 36	79.2 Percentage of participants Interval 74.4 to 84.1	82.6 Percentage of participants Interval 78.2 to 87.1	78.3 Percentage of participants Interval 73.5 to 83.1
Percentage of Participants Gaining ≥5 Letters in BCVA From Baseline in the Study Eye Over Time, ITT Population Week 40	76.3 Percentage of participants Interval 71.3 to 81.3	84.3 Percentage of participants Interval 80.0 to 88.6	77.1 Percentage of participants Interval 72.0 to 82.2
Percentage of Participants Gaining ≥5 Letters in BCVA From Baseline in the Study Eye Over Time, ITT Population Week 44	80.7 Percentage of participants Interval 75.9 to 85.4	81.9 Percentage of participants Interval 77.3 to 86.4	77.9 Percentage of participants Interval 73.0 to 82.7
Percentage of Participants Gaining ≥5 Letters in BCVA From Baseline in the Study Eye Over Time, ITT Population Week 48	79.2 Percentage of participants Interval 74.4 to 84.1	82.0 Percentage of participants Interval 77.5 to 86.6	79.3 Percentage of participants Interval 74.4 to 84.1
Percentage of Participants Gaining ≥5 Letters in BCVA From Baseline in the Study Eye Over Time, ITT Population Week 52	78.4 Percentage of participants Interval 73.5 to 83.4	78.4 Percentage of participants Interval 73.5 to 83.2	81.2 Percentage of participants Interval 76.4 to 85.9
Percentage of Participants Gaining ≥5 Letters in BCVA From Baseline in the Study Eye Over Time, ITT Population Week 56	83.0 Percentage of participants Interval 78.5 to 87.6	81.3 Percentage of participants Interval 76.6 to 86.0	81.4 Percentage of participants Interval 76.7 to 86.1
Percentage of Participants Gaining ≥5 Letters in BCVA From Baseline in the Study Eye Over Time, ITT Population Week 60	80.4 Percentage of participants Interval 75.7 to 85.1	81.3 Percentage of participants Interval 76.7 to 85.9	81.4 Percentage of participants Interval 76.8 to 86.1
Percentage of Participants Gaining ≥5 Letters in BCVA From Baseline in the Study Eye Over Time, ITT Population Week 64	80.2 Percentage of participants Interval 75.4 to 85.1	80.6 Percentage of participants Interval 75.9 to 85.2	79.7 Percentage of participants Interval 74.9 to 84.5
Percentage of Participants Gaining ≥5 Letters in BCVA From Baseline in the Study Eye Over Time, ITT Population Week 68	79.1 Percentage of participants Interval 74.1 to 84.0	78.9 Percentage of participants Interval 74.0 to 83.8	79.1 Percentage of participants Interval 74.2 to 84.0
Percentage of Participants Gaining ≥5 Letters in BCVA From Baseline in the Study Eye Over Time, ITT Population Week 72	79.7 Percentage of participants Interval 74.8 to 84.6	78.1 Percentage of participants Interval 73.2 to 83.0	80.9 Percentage of participants Interval 76.1 to 85.7
Percentage of Participants Gaining ≥5 Letters in BCVA From Baseline in the Study Eye Over Time, ITT Population Week 76	79.9 Percentage of participants Interval 74.9 to 84.8	78.9 Percentage of participants Interval 74.0 to 83.8	82.9 Percentage of participants Interval 78.3 to 87.5
Percentage of Participants Gaining ≥5 Letters in BCVA From Baseline in the Study Eye Over Time, ITT Population Week 80	81.0 Percentage of participants Interval 76.1 to 85.9	80.3 Percentage of participants Interval 75.5 to 85.0	78.3 Percentage of participants Interval 73.2 to 83.4
Percentage of Participants Gaining ≥5 Letters in BCVA From Baseline in the Study Eye Over Time, ITT Population Week 84	77.1 Percentage of participants Interval 71.9 to 82.3	82.0 Percentage of participants Interval 77.5 to 86.5	82.6 Percentage of participants Interval 77.9 to 87.2
Percentage of Participants Gaining ≥5 Letters in BCVA From Baseline in the Study Eye Over Time, ITT Population Week 88	79.3 Percentage of participants Interval 74.2 to 84.3	80.5 Percentage of participants Interval 75.8 to 85.2	80.5 Percentage of participants Interval 75.6 to 85.5
Percentage of Participants Gaining ≥5 Letters in BCVA From Baseline in the Study Eye Over Time, ITT Population Week 92	81.4 Percentage of participants Interval 76.6 to 86.3	82.1 Percentage of participants Interval 77.5 to 86.7	83.2 Percentage of participants Interval 78.6 to 87.7
Percentage of Participants Gaining ≥5 Letters in BCVA From Baseline in the Study Eye Over Time, ITT Population Week 96	82.6 Percentage of participants Interval 77.8 to 87.3	77.4 Percentage of participants Interval 72.5 to 82.4	81.2 Percentage of participants Interval 76.3 to 86.0
Percentage of Participants Gaining ≥5 Letters in BCVA From Baseline in the Study Eye Over Time, ITT Population Week 100	81.1 Percentage of participants Interval 76.3 to 85.9	77.0 Percentage of participants Interval 71.9 to 82.0	85.2 Percentage of participants Interval 80.9 to 89.6

SECONDARY outcome

Timeframe: Baseline, Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, 56, 60, 64, 68, 72, 76, 80, 84, 88, 92, 96, and 100

Best Corrected Visual Acuity (BCVA) was measured on the Early Treatment Diabetic Retinopathy Study (ETDRS) chart at a starting distance of 4 meters. The BCVA letter score ranges from 0 to 100 (best score), and a gain in BCVA letter score from baseline indicates an improvement in visual acuity. The weighted estimates of the percentage of participants were based on the Cochran-Mantel Haenszel (CMH) weights stratified by baseline BCVA (≥64 vs. \<64 letters), prior IVT anti-VEGF therapy (yes vs. no), and region (U.S. and Canada vs. rest of the world; Asia and rest of the world were combined). Treatment policy strategy (i.e., all observed values used) and hypothetical strategy (i.e., all values censored after the occurrence of the intercurrent event) were applied to non-COVID-19 related and COVID-19 related intercurrent events, respectively. Missing data were not imputed. Invalid BCVA values were excluded from analysis. 95% confidence interval (CI) is a rounding of 95.04% CI.

Outcome measures

Outcome measures
Measure	A: Faricimab 6 mg Q8W n=315 Participants Participants randomized to Arm A received 6 milligrams (mg) faricimab intravitreal (IVT) injections once every 4 weeks (Q4W) to Week 20, followed by 6 mg faricimab IVT injections once every 8 weeks (Q8W) to Week 96, followed by the final study visit at Week 100.	B: Faricimab 6 mg PTI n=313 Participants Participants randomized to Arm B received 6 milligrams (mg) faricimab intravitreal (IVT) injections Q4W to at least Week 12, followed by a personalized treatment interval (PTI) dosing of 6 mg faricimab IVT injections up to once every 16 weeks (Q16W) through Week 96, followed by the final study visit at Week 100.	C: Aflibercept 2 mg Q8W n=312 Participants Participants randomized to Arm C received 2 milligrams (mg) aflibercept intravitreal (IVT) injections Q4W to Week 16, followed by 2 mg aflibercept IVT injections Q8W to Week 96, followed by the final study visit at Week 100.
Percentage of Participants Gaining ≥0 Letters in BCVA From Baseline in the Study Eye Over Time, ITT Population Week 4	86.1 Percentage of participants Interval 82.3 to 90.0	90.8 Percentage of participants Interval 87.7 to 94.0	88.9 Percentage of participants Interval 85.4 to 92.3
Percentage of Participants Gaining ≥0 Letters in BCVA From Baseline in the Study Eye Over Time, ITT Population Week 8	89.7 Percentage of participants Interval 86.4 to 93.0	91.9 Percentage of participants Interval 88.8 to 94.9	91.1 Percentage of participants Interval 87.9 to 94.2
Percentage of Participants Gaining ≥0 Letters in BCVA From Baseline in the Study Eye Over Time, ITT Population Week 12	92.5 Percentage of participants Interval 89.6 to 95.4	94.7 Percentage of participants Interval 92.2 to 97.2	92.7 Percentage of participants Interval 89.8 to 95.6
Percentage of Participants Gaining ≥0 Letters in BCVA From Baseline in the Study Eye Over Time, ITT Population Week 16	91.2 Percentage of participants Interval 88.0 to 94.4	94.9 Percentage of participants Interval 92.4 to 97.4	93.7 Percentage of participants Interval 90.9 to 96.4
Percentage of Participants Gaining ≥0 Letters in BCVA From Baseline in the Study Eye Over Time, ITT Population Week 20	93.9 Percentage of participants Interval 91.2 to 96.6	93.1 Percentage of participants Interval 90.2 to 96.0	92.2 Percentage of participants Interval 89.2 to 95.2
Percentage of Participants Gaining ≥0 Letters in BCVA From Baseline in the Study Eye Over Time, ITT Population Week 24	93.1 Percentage of participants Interval 90.2 to 96.0	93.8 Percentage of participants Interval 91.0 to 96.5	89.9 Percentage of participants Interval 86.5 to 93.3
Percentage of Participants Gaining ≥0 Letters in BCVA From Baseline in the Study Eye Over Time, ITT Population Week 28	90.4 Percentage of participants Interval 87.0 to 93.8	94.1 Percentage of participants Interval 91.4 to 96.8	91.5 Percentage of participants Interval 88.3 to 94.6
Percentage of Participants Gaining ≥0 Letters in BCVA From Baseline in the Study Eye Over Time, ITT Population Week 32	92.1 Percentage of participants Interval 88.9 to 95.3	95.1 Percentage of participants Interval 92.6 to 97.7	91.3 Percentage of participants Interval 88.0 to 94.6
Percentage of Participants Gaining ≥0 Letters in BCVA From Baseline in the Study Eye Over Time, ITT Population Week 36	92.1 Percentage of participants Interval 88.9 to 95.3	93.2 Percentage of participants Interval 90.2 to 96.2	90.4 Percentage of participants Interval 87.0 to 93.9
Percentage of Participants Gaining ≥0 Letters in BCVA From Baseline in the Study Eye Over Time, ITT Population Week 40	90.9 Percentage of participants Interval 87.5 to 94.3	94.0 Percentage of participants Interval 91.1 to 96.8	93.2 Percentage of participants Interval 90.2 to 96.2
Percentage of Participants Gaining ≥0 Letters in BCVA From Baseline in the Study Eye Over Time, ITT Population Week 44	91.0 Percentage of participants Interval 87.6 to 94.4	94.5 Percentage of participants Interval 91.8 to 97.2	91.0 Percentage of participants Interval 87.6 to 94.4
Percentage of Participants Gaining ≥0 Letters in BCVA From Baseline in the Study Eye Over Time, ITT Population Week 48	95.2 Percentage of participants Interval 92.6 to 97.7	93.7 Percentage of participants Interval 90.8 to 96.5	91.3 Percentage of participants Interval 88.0 to 94.6
Percentage of Participants Gaining ≥0 Letters in BCVA From Baseline in the Study Eye Over Time, ITT Population Week 52	89.8 Percentage of participants Interval 86.1 to 93.4	91.3 Percentage of participants Interval 88.0 to 94.7	91.0 Percentage of participants Interval 87.5 to 94.5
Percentage of Participants Gaining ≥0 Letters in BCVA From Baseline in the Study Eye Over Time, ITT Population Week 56	91.4 Percentage of participants Interval 88.0 to 94.8	93.9 Percentage of participants Interval 91.0 to 96.7	90.6 Percentage of participants Interval 87.1 to 94.2
Percentage of Participants Gaining ≥0 Letters in BCVA From Baseline in the Study Eye Over Time, ITT Population Week 60	89.5 Percentage of participants Interval 85.9 to 93.2	93.5 Percentage of participants Interval 90.5 to 96.4	92.8 Percentage of participants Interval 89.7 to 95.9
Percentage of Participants Gaining ≥0 Letters in BCVA From Baseline in the Study Eye Over Time, ITT Population Week 64	91.3 Percentage of participants Interval 87.9 to 94.7	92.7 Percentage of participants Interval 89.6 to 95.8	92.0 Percentage of participants Interval 88.7 to 95.2
Percentage of Participants Gaining ≥0 Letters in BCVA From Baseline in the Study Eye Over Time, ITT Population Week 68	92.1 Percentage of participants Interval 88.8 to 95.4	92.9 Percentage of participants Interval 89.8 to 96.0	91.9 Percentage of participants Interval 88.6 to 95.2
Percentage of Participants Gaining ≥0 Letters in BCVA From Baseline in the Study Eye Over Time, ITT Population Week 72	88.5 Percentage of participants Interval 84.6 to 92.5	91.9 Percentage of participants Interval 88.7 to 95.2	90.0 Percentage of participants Interval 86.3 to 93.7
Percentage of Participants Gaining ≥0 Letters in BCVA From Baseline in the Study Eye Over Time, ITT Population Week 76	87.8 Percentage of participants Interval 83.8 to 91.9	91.2 Percentage of participants Interval 87.8 to 94.7	92.5 Percentage of participants Interval 89.4 to 95.7
Percentage of Participants Gaining ≥0 Letters in BCVA From Baseline in the Study Eye Over Time, ITT Population Week 80	89.2 Percentage of participants Interval 85.4 to 93.0	91.5 Percentage of participants Interval 88.1 to 94.9	89.6 Percentage of participants Interval 85.9 to 93.4
Percentage of Participants Gaining ≥0 Letters in BCVA From Baseline in the Study Eye Over Time, ITT Population Week 84	87.1 Percentage of participants Interval 82.9 to 91.2	92.4 Percentage of participants Interval 89.2 to 95.6	93.5 Percentage of participants Interval 90.5 to 96.5
Percentage of Participants Gaining ≥0 Letters in BCVA From Baseline in the Study Eye Over Time, ITT Population Week 88	87.3 Percentage of participants Interval 83.2 to 91.4	90.3 Percentage of participants Interval 86.7 to 93.8	89.9 Percentage of participants Interval 86.1 to 93.7
Percentage of Participants Gaining ≥0 Letters in BCVA From Baseline in the Study Eye Over Time, ITT Population Week 92	89.4 Percentage of participants Interval 85.5 to 93.2	91.1 Percentage of participants Interval 87.6 to 94.6	90.8 Percentage of participants Interval 87.3 to 94.3
Percentage of Participants Gaining ≥0 Letters in BCVA From Baseline in the Study Eye Over Time, ITT Population Week 96	90.7 Percentage of participants Interval 87.0 to 94.4	88.9 Percentage of participants Interval 85.1 to 92.6	90.5 Percentage of participants Interval 86.8 to 94.2
Percentage of Participants Gaining ≥0 Letters in BCVA From Baseline in the Study Eye Over Time, ITT Population Week 100	88.3 Percentage of participants Interval 84.3 to 92.3	86.8 Percentage of participants Interval 82.7 to 90.9	92.0 Percentage of participants Interval 88.7 to 95.4

SECONDARY outcome

Timeframe: Baseline, average of Weeks 48, 52, and 56

Population: Treatment-Naive Population: all participants randomized in the study who had not received any intravitreal anti-VEGF agents in the study eye prior to randomization. Participants were grouped according to the treatment assigned at randomization. Only participants with at least one non-missing, valid assessment at Weeks 48, 52, or 56 were included in the analysis.

BCVA was measured on the ETDRS chart at a starting distance of 4 meters. The BCVA letter score ranges from 0 to 100 (best score), and a gain in BCVA from baseline indicates an improvement in visual acuity. For each participant, an average BCVA value was calculated across the three visits, and this averaged value was then used to determine if the endpoint was met. The results were summarized as the percentage of participants per treatment arm who met the endpoint. The weighted estimates of the percentage of participants were based on the Cochran-Mantel Haenszel (CMH) weights stratified by baseline BCVA (≥64 vs. \<64 letters) and region (U.S. and Canada vs. rest of the world). Treatment policy strategy and hypothetical strategy were applied to non-COVID-19 related and COVID-19 related intercurrent events, respectively. Missing data were not imputed. Invalid BCVA values were excluded. 95% confidence interval (CI) is a rounding of 95.04% CI.

Outcome measures

Outcome measures
Measure	A: Faricimab 6 mg Q8W n=200 Participants Participants randomized to Arm A received 6 milligrams (mg) faricimab intravitreal (IVT) injections once every 4 weeks (Q4W) to Week 20, followed by 6 mg faricimab IVT injections once every 8 weeks (Q8W) to Week 96, followed by the final study visit at Week 100.	B: Faricimab 6 mg PTI n=215 Participants Participants randomized to Arm B received 6 milligrams (mg) faricimab intravitreal (IVT) injections Q4W to at least Week 12, followed by a personalized treatment interval (PTI) dosing of 6 mg faricimab IVT injections up to once every 16 weeks (Q16W) through Week 96, followed by the final study visit at Week 100.	C: Aflibercept 2 mg Q8W n=212 Participants Participants randomized to Arm C received 2 milligrams (mg) aflibercept intravitreal (IVT) injections Q4W to Week 16, followed by 2 mg aflibercept IVT injections Q8W to Week 96, followed by the final study visit at Week 100.
Percentage of Participants Gaining ≥15, ≥10, ≥5, or ≥0 Letters in BCVA From Baseline in the Study Eye Averaged Over Weeks 48, 52, and 56, Treatment-Naive Population Gaining ≥15 Letters	28.6 Percentage of participants Interval 22.3 to 34.8	35.5 Percentage of participants Interval 29.3 to 41.7	33.8 Percentage of participants Interval 27.7 to 39.9
Percentage of Participants Gaining ≥15, ≥10, ≥5, or ≥0 Letters in BCVA From Baseline in the Study Eye Averaged Over Weeks 48, 52, and 56, Treatment-Naive Population Gaining ≥10 Letters	57.5 Percentage of participants Interval 50.7 to 64.4	59.6 Percentage of participants Interval 53.2 to 65.9	57.5 Percentage of participants Interval 50.9 to 64.1
Percentage of Participants Gaining ≥15, ≥10, ≥5, or ≥0 Letters in BCVA From Baseline in the Study Eye Averaged Over Weeks 48, 52, and 56, Treatment-Naive Population Gaining ≥5 Letters	80.0 Percentage of participants Interval 74.4 to 85.5	77.2 Percentage of participants Interval 71.6 to 82.8	84.5 Percentage of participants Interval 79.6 to 89.3
Percentage of Participants Gaining ≥15, ≥10, ≥5, or ≥0 Letters in BCVA From Baseline in the Study Eye Averaged Over Weeks 48, 52, and 56, Treatment-Naive Population Gaining ≥0 Letters	91.5 Percentage of participants Interval 87.6 to 95.3	93.5 Percentage of participants Interval 90.2 to 96.8	91.6 Percentage of participants Interval 87.9 to 95.3

SECONDARY outcome

Timeframe: Baseline, Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, 56, 60, 64, 68, 72, 76, 80, 84, 88, 92, 96, and 100

Population: Treatment-Naive Population: all participants randomized in the study who had not received any intravitreal anti-VEGF agents in the study eye prior to randomization. Participants were grouped according to the treatment assigned at randomization. At each timepoint, only participants with non-missing, valid assessments were included in the analysis.

Best Corrected Visual Acuity (BCVA) was measured on the Early Treatment Diabetic Retinopathy Study (ETDRS) chart at a starting distance of 4 meters. The BCVA letter score ranges from 0 to 100 (best score), and a gain in BCVA letter score from baseline indicates an improvement in visual acuity. The weighted estimates of the percentage of participants were based on the Cochran-Mantel Haenszel (CMH) weights stratified by baseline BCVA (≥64 vs. \<64 letters) and region (U.S. and Canada vs. rest of the world; Asia and rest of the world were combined). Treatment policy strategy (i.e., all observed values used) and hypothetical strategy (i.e., all values censored after the occurrence of the intercurrent event) were applied to non-COVID-19 related and COVID-19 related intercurrent events, respectively. Missing data were not imputed. Invalid BCVA values were excluded from analysis. 95% confidence interval (CI) is a rounding of 95.04% CI.

Outcome measures

Outcome measures
Measure	A: Faricimab 6 mg Q8W n=238 Participants Participants randomized to Arm A received 6 milligrams (mg) faricimab intravitreal (IVT) injections once every 4 weeks (Q4W) to Week 20, followed by 6 mg faricimab IVT injections once every 8 weeks (Q8W) to Week 96, followed by the final study visit at Week 100.	B: Faricimab 6 mg PTI n=245 Participants Participants randomized to Arm B received 6 milligrams (mg) faricimab intravitreal (IVT) injections Q4W to at least Week 12, followed by a personalized treatment interval (PTI) dosing of 6 mg faricimab IVT injections up to once every 16 weeks (Q16W) through Week 96, followed by the final study visit at Week 100.	C: Aflibercept 2 mg Q8W n=242 Participants Participants randomized to Arm C received 2 milligrams (mg) aflibercept intravitreal (IVT) injections Q4W to Week 16, followed by 2 mg aflibercept IVT injections Q8W to Week 96, followed by the final study visit at Week 100.
Percentage of Participants Gaining ≥15 Letters in BCVA From Baseline in the Study Eye Over Time, Treatment-Naive Population Week 4	8.9 Percentage of participants Interval 5.3 to 12.5	14.9 Percentage of participants Interval 10.6 to 19.3	12.7 Percentage of participants Interval 8.6 to 16.9
Percentage of Participants Gaining ≥15 Letters in BCVA From Baseline in the Study Eye Over Time, Treatment-Naive Population Week 8	14.3 Percentage of participants Interval 9.9 to 18.8	19.2 Percentage of participants Interval 14.6 to 23.8	17.8 Percentage of participants Interval 13.1 to 22.6
Percentage of Participants Gaining ≥15 Letters in BCVA From Baseline in the Study Eye Over Time, Treatment-Naive Population Week 12	15.7 Percentage of participants Interval 11.1 to 20.3	22.2 Percentage of participants Interval 17.2 to 27.1	24.2 Percentage of participants Interval 19.0 to 29.5
Percentage of Participants Gaining ≥15 Letters in BCVA From Baseline in the Study Eye Over Time, Treatment-Naive Population Week 16	21.3 Percentage of participants Interval 16.0 to 26.6	28.2 Percentage of participants Interval 22.6 to 33.8	24.0 Percentage of participants Interval 18.6 to 29.3
Percentage of Participants Gaining ≥15 Letters in BCVA From Baseline in the Study Eye Over Time, Treatment-Naive Population Week 20	26.5 Percentage of participants Interval 20.8 to 32.2	27.7 Percentage of participants Interval 22.2 to 33.3	26.2 Percentage of participants Interval 20.7 to 31.6
Percentage of Participants Gaining ≥15 Letters in BCVA From Baseline in the Study Eye Over Time, Treatment-Naive Population Week 24	27.1 Percentage of participants Interval 21.3 to 32.9	34.3 Percentage of participants Interval 28.4 to 40.2	27.5 Percentage of participants Interval 22.0 to 33.1
Percentage of Participants Gaining ≥15 Letters in BCVA From Baseline in the Study Eye Over Time, Treatment-Naive Population Week 28	21.5 Percentage of participants Interval 16.0 to 27.0	30.7 Percentage of participants Interval 25.0 to 36.4	32.8 Percentage of participants Interval 26.8 to 38.7
Percentage of Participants Gaining ≥15 Letters in BCVA From Baseline in the Study Eye Over Time, Treatment-Naive Population Week 32	27.2 Percentage of participants Interval 21.0 to 33.5	37.5 Percentage of participants Interval 31.2 to 43.8	29.5 Percentage of participants Interval 23.6 to 35.4
Percentage of Participants Gaining ≥15 Letters in BCVA From Baseline in the Study Eye Over Time, Treatment-Naive Population Week 36	23.5 Percentage of participants Interval 17.6 to 29.5	41.9 Percentage of participants Interval 35.5 to 48.2	34.9 Percentage of participants Interval 28.6 to 41.2
Percentage of Participants Gaining ≥15 Letters in BCVA From Baseline in the Study Eye Over Time, Treatment-Naive Population Week 40	27.6 Percentage of participants Interval 21.5 to 33.8	37.7 Percentage of participants Interval 31.2 to 44.1	33.5 Percentage of participants Interval 27.0 to 39.9
Percentage of Participants Gaining ≥15 Letters in BCVA From Baseline in the Study Eye Over Time, Treatment-Naive Population Week 44	27.2 Percentage of participants Interval 21.1 to 33.4	39.7 Percentage of participants Interval 33.3 to 46.0	37.0 Percentage of participants Interval 30.6 to 43.4
Percentage of Participants Gaining ≥15 Letters in BCVA From Baseline in the Study Eye Over Time, Treatment-Naive Population Week 48	32.5 Percentage of participants Interval 26.0 to 39.1	39.6 Percentage of participants Interval 33.1 to 46.0	36.3 Percentage of participants Interval 30.1 to 42.5
Percentage of Participants Gaining ≥15 Letters in BCVA From Baseline in the Study Eye Over Time, Treatment-Naive Population Week 52	30.7 Percentage of participants Interval 24.3 to 37.1	35.9 Percentage of participants Interval 29.6 to 42.1	37.4 Percentage of participants Interval 30.9 to 43.9
Percentage of Participants Gaining ≥15 Letters in BCVA From Baseline in the Study Eye Over Time, Treatment-Naive Population Week 56	37.7 Percentage of participants Interval 31.0 to 44.5	38.8 Percentage of participants Interval 32.3 to 45.2	34.3 Percentage of participants Interval 27.9 to 40.8
Percentage of Participants Gaining ≥15 Letters in BCVA From Baseline in the Study Eye Over Time, Treatment-Naive Population Week 60	33.1 Percentage of participants Interval 26.6 to 39.6	42.2 Percentage of participants Interval 35.6 to 48.9	38.9 Percentage of participants Interval 32.4 to 45.5
Percentage of Participants Gaining ≥15 Letters in BCVA From Baseline in the Study Eye Over Time, Treatment-Naive Population Week 64	37.9 Percentage of participants Interval 31.1 to 44.7	43.5 Percentage of participants Interval 37.0 to 50.0	36.0 Percentage of participants Interval 29.5 to 42.6
Percentage of Participants Gaining ≥15 Letters in BCVA From Baseline in the Study Eye Over Time, Treatment-Naive Population Week 68	37.4 Percentage of participants Interval 30.7 to 44.2	45.4 Percentage of participants Interval 38.7 to 52.1	39.0 Percentage of participants Interval 32.4 to 45.5
Percentage of Participants Gaining ≥15 Letters in BCVA From Baseline in the Study Eye Over Time, Treatment-Naive Population Week 72	35.6 Percentage of participants Interval 28.8 to 42.4	39.6 Percentage of participants Interval 33.1 to 46.0	36.6 Percentage of participants Interval 29.8 to 43.3
Percentage of Participants Gaining ≥15 Letters in BCVA From Baseline in the Study Eye Over Time, Treatment-Naive Population Week 76	37.6 Percentage of participants Interval 30.6 to 44.6	45.3 Percentage of participants Interval 38.8 to 51.8	37.2 Percentage of participants Interval 30.5 to 43.9
Percentage of Participants Gaining ≥15 Letters in BCVA From Baseline in the Study Eye Over Time, Treatment-Naive Population Week 80	39.7 Percentage of participants Interval 32.7 to 46.8	43.2 Percentage of participants Interval 36.8 to 49.7	40.5 Percentage of participants Interval 33.6 to 47.3
Percentage of Participants Gaining ≥15 Letters in BCVA From Baseline in the Study Eye Over Time, Treatment-Naive Population Week 84	40.7 Percentage of participants Interval 33.7 to 47.8	43.2 Percentage of participants Interval 36.8 to 49.7	41.2 Percentage of participants Interval 34.3 to 48.1
Percentage of Participants Gaining ≥15 Letters in BCVA From Baseline in the Study Eye Over Time, Treatment-Naive Population Week 88	39.1 Percentage of participants Interval 32.1 to 46.2	40.7 Percentage of participants Interval 34.4 to 47.1	38.0 Percentage of participants Interval 31.2 to 44.8
Percentage of Participants Gaining ≥15 Letters in BCVA From Baseline in the Study Eye Over Time, Treatment-Naive Population Week 92	40.2 Percentage of participants Interval 33.2 to 47.3	42.1 Percentage of participants Interval 35.7 to 48.5	40.4 Percentage of participants Interval 33.6 to 47.3
Percentage of Participants Gaining ≥15 Letters in BCVA From Baseline in the Study Eye Over Time, Treatment-Naive Population Week 96	42.9 Percentage of participants Interval 35.6 to 50.2	41.2 Percentage of participants Interval 34.9 to 47.6	40.1 Percentage of participants Interval 33.2 to 47.0
Percentage of Participants Gaining ≥15 Letters in BCVA From Baseline in the Study Eye Over Time, Treatment-Naive Population Week 100	41.7 Percentage of participants Interval 34.6 to 48.7	42.5 Percentage of participants Interval 36.1 to 48.9	41.2 Percentage of participants Interval 34.3 to 48.1

SECONDARY outcome

Timeframe: Baseline, Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, 56, 60, 64, 68, 72, 76, 80, 84, 88, 92, 96, and 100

Population: Treatment-Naive Population: all participants randomized in the study who had not received any intravitreal anti-VEGF agents in the study eye prior to randomization. Participants were grouped according to the treatment assigned at randomization. At each timepoint, only participants with non-missing, valid assessments were included in the analysis.

Best Corrected Visual Acuity (BCVA) was measured on the Early Treatment Diabetic Retinopathy Study (ETDRS) chart at a starting distance of 4 meters. The BCVA letter score ranges from 0 to 100 (best score), and a gain in BCVA letter score from baseline indicates an improvement in visual acuity. The weighted estimates of the percentage of participants were based on the Cochran-Mantel Haenszel (CMH) weights stratified by baseline BCVA (≥64 vs. \<64 letters) and region (U.S. and Canada vs. rest of the world; Asia and rest of the world were combined). Treatment policy strategy (i.e., all observed values used) and hypothetical strategy (i.e., all values censored after the occurrence of the intercurrent event) were applied to non-COVID-19 related and COVID-19 related intercurrent events, respectively. Missing data were not imputed. Invalid BCVA values were excluded from analysis. 95% confidence interval (CI) is a rounding of 95.04% CI.

Outcome measures

Outcome measures
Measure	A: Faricimab 6 mg Q8W n=238 Participants Participants randomized to Arm A received 6 milligrams (mg) faricimab intravitreal (IVT) injections once every 4 weeks (Q4W) to Week 20, followed by 6 mg faricimab IVT injections once every 8 weeks (Q8W) to Week 96, followed by the final study visit at Week 100.	B: Faricimab 6 mg PTI n=245 Participants Participants randomized to Arm B received 6 milligrams (mg) faricimab intravitreal (IVT) injections Q4W to at least Week 12, followed by a personalized treatment interval (PTI) dosing of 6 mg faricimab IVT injections up to once every 16 weeks (Q16W) through Week 96, followed by the final study visit at Week 100.	C: Aflibercept 2 mg Q8W n=242 Participants Participants randomized to Arm C received 2 milligrams (mg) aflibercept intravitreal (IVT) injections Q4W to Week 16, followed by 2 mg aflibercept IVT injections Q8W to Week 96, followed by the final study visit at Week 100.
Percentage of Participants Gaining ≥10 Letters in BCVA From Baseline in the Study Eye Over Time, Treatment-Naive Population Week 12	36.9 Percentage of participants Interval 30.8 to 43.1	46.5 Percentage of participants Interval 40.3 to 52.6	48.9 Percentage of participants Interval 42.6 to 55.2
Percentage of Participants Gaining ≥10 Letters in BCVA From Baseline in the Study Eye Over Time, Treatment-Naive Population Week 16	43.8 Percentage of participants Interval 37.3 to 50.3	47.8 Percentage of participants Interval 41.4 to 54.1	49.8 Percentage of participants Interval 43.5 to 56.2
Percentage of Participants Gaining ≥10 Letters in BCVA From Baseline in the Study Eye Over Time, Treatment-Naive Population Week 20	44.9 Percentage of participants Interval 38.4 to 51.4	53.7 Percentage of participants Interval 47.5 to 59.9	51.5 Percentage of participants Interval 45.1 to 57.9
Percentage of Participants Gaining ≥10 Letters in BCVA From Baseline in the Study Eye Over Time, Treatment-Naive Population Week 24	57.6 Percentage of participants Interval 51.1 to 64.1	57.9 Percentage of participants Interval 51.7 to 64.2	49.9 Percentage of participants Interval 43.5 to 56.3
Percentage of Participants Gaining ≥10 Letters in BCVA From Baseline in the Study Eye Over Time, Treatment-Naive Population Week 28	55.3 Percentage of participants Interval 48.6 to 61.9	56.6 Percentage of participants Interval 50.3 to 62.9	57.4 Percentage of participants Interval 50.8 to 63.9
Percentage of Participants Gaining ≥10 Letters in BCVA From Baseline in the Study Eye Over Time, Treatment-Naive Population Week 32	59.0 Percentage of participants Interval 52.2 to 65.9	59.6 Percentage of participants Interval 53.1 to 66.0	53.1 Percentage of participants Interval 46.5 to 59.7
Percentage of Participants Gaining ≥10 Letters in BCVA From Baseline in the Study Eye Over Time, Treatment-Naive Population Week 36	59.0 Percentage of participants Interval 52.1 to 65.9	66.3 Percentage of participants Interval 60.0 to 72.5	55.8 Percentage of participants Interval 49.1 to 62.5
Percentage of Participants Gaining ≥10 Letters in BCVA From Baseline in the Study Eye Over Time, Treatment-Naive Population Week 40	55.5 Percentage of participants Interval 48.7 to 62.4	59.7 Percentage of participants Interval 53.1 to 66.4	54.5 Percentage of participants Interval 47.7 to 61.4
Percentage of Participants Gaining ≥10 Letters in BCVA From Baseline in the Study Eye Over Time, Treatment-Naive Population Week 44	55.0 Percentage of participants Interval 48.1 to 61.9	59.2 Percentage of participants Interval 52.7 to 65.7	58.1 Percentage of participants Interval 51.3 to 64.8
Percentage of Participants Gaining ≥10 Letters in BCVA From Baseline in the Study Eye Over Time, Treatment-Naive Population Week 48	57.1 Percentage of participants Interval 50.2 to 64.0	58.5 Percentage of participants Interval 52.0 to 65.0	62.6 Percentage of participants Interval 56.0 to 69.2
Percentage of Participants Gaining ≥10 Letters in BCVA From Baseline in the Study Eye Over Time, Treatment-Naive Population Week 52	60.0 Percentage of participants Interval 53.1 to 66.8	58.8 Percentage of participants Interval 52.2 to 65.3	61.0 Percentage of participants Interval 54.2 to 67.8
Percentage of Participants Gaining ≥10 Letters in BCVA From Baseline in the Study Eye Over Time, Treatment-Naive Population Week 56	65.0 Percentage of participants Interval 58.3 to 71.7	62.9 Percentage of participants Interval 56.5 to 69.3	60.1 Percentage of participants Interval 53.4 to 66.8
Percentage of Participants Gaining ≥10 Letters in BCVA From Baseline in the Study Eye Over Time, Treatment-Naive Population Week 60	61.5 Percentage of participants Interval 54.7 to 68.2	63.4 Percentage of participants Interval 56.9 to 69.9	61.3 Percentage of participants Interval 54.5 to 68.0
Percentage of Participants Gaining ≥10 Letters in BCVA From Baseline in the Study Eye Over Time, Treatment-Naive Population Week 64	67.7 Percentage of participants Interval 61.1 to 74.3	59.8 Percentage of participants Interval 53.3 to 66.2	59.7 Percentage of participants Interval 53.0 to 66.4
Percentage of Participants Gaining ≥10 Letters in BCVA From Baseline in the Study Eye Over Time, Treatment-Naive Population Week 68	64.1 Percentage of participants Interval 57.4 to 70.8	60.7 Percentage of participants Interval 54.2 to 67.2	60.6 Percentage of participants Interval 53.9 to 67.3
Percentage of Participants Gaining ≥10 Letters in BCVA From Baseline in the Study Eye Over Time, Treatment-Naive Population Week 72	62.6 Percentage of participants Interval 55.8 to 69.5	62.5 Percentage of participants Interval 56.0 to 69.0	56.7 Percentage of participants Interval 49.8 to 63.7
Percentage of Participants Gaining ≥10 Letters in BCVA From Baseline in the Study Eye Over Time, Treatment-Naive Population Week 76	61.8 Percentage of participants Interval 54.8 to 68.9	66.8 Percentage of participants Interval 60.5 to 73.0	66.2 Percentage of participants Interval 59.6 to 72.9
Percentage of Participants Gaining ≥10 Letters in BCVA From Baseline in the Study Eye Over Time, Treatment-Naive Population Week 80	66.7 Percentage of participants Interval 59.8 to 73.5	62.4 Percentage of participants Interval 56.0 to 68.8	62.8 Percentage of participants Interval 56.0 to 69.6
Percentage of Participants Gaining ≥10 Letters in BCVA From Baseline in the Study Eye Over Time, Treatment-Naive Population Week 84	63.2 Percentage of participants Interval 56.3 to 70.1	65.3 Percentage of participants Interval 59.0 to 71.6	67.1 Percentage of participants Interval 60.5 to 73.6
Percentage of Participants Gaining ≥10 Letters in BCVA From Baseline in the Study Eye Over Time, Treatment-Naive Population Week 88	60.2 Percentage of participants Interval 53.2 to 67.3	60.9 Percentage of participants Interval 54.3 to 67.6	61.9 Percentage of participants Interval 55.1 to 68.7
Percentage of Participants Gaining ≥10 Letters in BCVA From Baseline in the Study Eye Over Time, Treatment-Naive Population Week 92	63.2 Percentage of participants Interval 56.2 to 70.2	65.1 Percentage of participants Interval 58.7 to 71.5	65.0 Percentage of participants Interval 58.2 to 71.7
Percentage of Participants Gaining ≥10 Letters in BCVA From Baseline in the Study Eye Over Time, Treatment-Naive Population Week 96	58.8 Percentage of participants Interval 51.5 to 66.0	60.6 Percentage of participants Interval 54.0 to 67.1	63.8 Percentage of participants Interval 56.9 to 70.6
Percentage of Participants Gaining ≥10 Letters in BCVA From Baseline in the Study Eye Over Time, Treatment-Naive Population Week 100	64.0 Percentage of participants Interval 57.3 to 70.7	62.4 Percentage of participants Interval 56.0 to 68.8	64.8 Percentage of participants Interval 58.0 to 71.6
Percentage of Participants Gaining ≥10 Letters in BCVA From Baseline in the Study Eye Over Time, Treatment-Naive Population Week 4	25.2 Percentage of participants Interval 19.7 to 30.7	32.0 Percentage of participants Interval 26.3 to 37.7	29.2 Percentage of participants Interval 23.5 to 35.0
Percentage of Participants Gaining ≥10 Letters in BCVA From Baseline in the Study Eye Over Time, Treatment-Naive Population Week 8	31.1 Percentage of participants Interval 25.2 to 37.1	37.2 Percentage of participants Interval 31.3 to 43.1	43.9 Percentage of participants Interval 37.7 to 50.2

SECONDARY outcome

Timeframe: Baseline, Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, 56, 60, 64, 68, 72, 76, 80, 84, 88, 92, 96, and 100

Population: Treatment-Naive Population: all participants randomized in the study who had not received any intravitreal anti-VEGF agents in the study eye prior to randomization. Participants were grouped according to the treatment assigned at randomization. At each timepoint, only participants with non-missing, valid assessments were included in the analysis.

Best Corrected Visual Acuity (BCVA) was measured on the Early Treatment Diabetic Retinopathy Study (ETDRS) chart at a starting distance of 4 meters. The BCVA letter score ranges from 0 to 100 (best score), and a gain in BCVA letter score from baseline indicates an improvement in visual acuity. The weighted estimates of the percentage of participants were based on the Cochran-Mantel Haenszel (CMH) weights stratified by baseline BCVA (≥64 vs. \<64 letters) and region (U.S. and Canada vs. rest of the world; Asia and rest of the world were combined). Treatment policy strategy (i.e., all observed values used) and hypothetical strategy (i.e., all values censored after the occurrence of the intercurrent event) were applied to non-COVID-19 related and COVID-19 related intercurrent events, respectively. Missing data were not imputed. Invalid BCVA values were excluded from analysis. 95% confidence interval (CI) is a rounding of 95.04% CI.

Outcome measures

Outcome measures
Measure	A: Faricimab 6 mg Q8W n=238 Participants Participants randomized to Arm A received 6 milligrams (mg) faricimab intravitreal (IVT) injections once every 4 weeks (Q4W) to Week 20, followed by 6 mg faricimab IVT injections once every 8 weeks (Q8W) to Week 96, followed by the final study visit at Week 100.	B: Faricimab 6 mg PTI n=245 Participants Participants randomized to Arm B received 6 milligrams (mg) faricimab intravitreal (IVT) injections Q4W to at least Week 12, followed by a personalized treatment interval (PTI) dosing of 6 mg faricimab IVT injections up to once every 16 weeks (Q16W) through Week 96, followed by the final study visit at Week 100.	C: Aflibercept 2 mg Q8W n=242 Participants Participants randomized to Arm C received 2 milligrams (mg) aflibercept intravitreal (IVT) injections Q4W to Week 16, followed by 2 mg aflibercept IVT injections Q8W to Week 96, followed by the final study visit at Week 100.
Percentage of Participants Gaining ≥5 Letters in BCVA From Baseline in the Study Eye Over Time, Treatment-Naive Population Week 4	53.8 Percentage of participants Interval 47.5 to 60.2	63.1 Percentage of participants Interval 57.1 to 69.1	62.8 Percentage of participants Interval 56.7 to 68.9
Percentage of Participants Gaining ≥5 Letters in BCVA From Baseline in the Study Eye Over Time, Treatment-Naive Population Week 8	63.4 Percentage of participants Interval 57.2 to 69.6	70.5 Percentage of participants Interval 64.8 to 76.2	70.4 Percentage of participants Interval 64.6 to 76.2
Percentage of Participants Gaining ≥5 Letters in BCVA From Baseline in the Study Eye Over Time, Treatment-Naive Population Week 12	72.7 Percentage of participants Interval 66.9 to 78.4	75.4 Percentage of participants Interval 69.9 to 80.8	77.0 Percentage of participants Interval 71.6 to 82.4
Percentage of Participants Gaining ≥5 Letters in BCVA From Baseline in the Study Eye Over Time, Treatment-Naive Population Week 16	75.6 Percentage of participants Interval 70.0 to 81.3	81.3 Percentage of participants Interval 76.3 to 86.3	79.3 Percentage of participants Interval 74.1 to 84.5
Percentage of Participants Gaining ≥5 Letters in BCVA From Baseline in the Study Eye Over Time, Treatment-Naive Population Week 20	79.0 Percentage of participants Interval 73.6 to 84.3	79.3 Percentage of participants Interval 74.0 to 84.6	78.2 Percentage of participants Interval 72.9 to 83.5
Percentage of Participants Gaining ≥5 Letters in BCVA From Baseline in the Study Eye Over Time, Treatment-Naive Population Week 24	81.7 Percentage of participants Interval 76.6 to 86.8	82.9 Percentage of participants Interval 78.1 to 87.7	71.4 Percentage of participants Interval 65.5 to 77.2
Percentage of Participants Gaining ≥5 Letters in BCVA From Baseline in the Study Eye Over Time, Treatment-Naive Population Week 28	76.9 Percentage of participants Interval 71.2 to 82.5	81.7 Percentage of participants Interval 76.6 to 86.7	80.0 Percentage of participants Interval 74.8 to 85.3
Percentage of Participants Gaining ≥5 Letters in BCVA From Baseline in the Study Eye Over Time, Treatment-Naive Population Week 32	80.0 Percentage of participants Interval 74.4 to 85.6	77.6 Percentage of participants Interval 72.0 to 83.1	83.7 Percentage of participants Interval 78.8 to 88.7
Percentage of Participants Gaining ≥5 Letters in BCVA From Baseline in the Study Eye Over Time, Treatment-Naive Population Week 36	80.5 Percentage of participants Interval 74.9 to 86.1	82.9 Percentage of participants Interval 77.9 to 88.0	79.6 Percentage of participants Interval 74.1 to 85.1
Percentage of Participants Gaining ≥5 Letters in BCVA From Baseline in the Study Eye Over Time, Treatment-Naive Population Week 40	77.1 Percentage of participants Interval 71.3 to 82.8	85.3 Percentage of participants Interval 80.5 to 90.1	80.0 Percentage of participants Interval 74.5 to 85.6
Percentage of Participants Gaining ≥5 Letters in BCVA From Baseline in the Study Eye Over Time, Treatment-Naive Population Week 44	81.4 Percentage of participants Interval 76.0 to 86.8	82.5 Percentage of participants Interval 77.4 to 87.6	80.8 Percentage of participants Interval 75.4 to 86.2
Percentage of Participants Gaining ≥5 Letters in BCVA From Baseline in the Study Eye Over Time, Treatment-Naive Population Week 48	79.5 Percentage of participants Interval 73.8 to 85.2	80.0 Percentage of participants Interval 74.6 to 85.4	80.8 Percentage of participants Interval 75.4 to 86.2
Percentage of Participants Gaining ≥5 Letters in BCVA From Baseline in the Study Eye Over Time, Treatment-Naive Population Week 52	78.7 Percentage of participants Interval 72.9 to 84.4	75.3 Percentage of participants Interval 69.5 to 81.1	82.3 Percentage of participants Interval 77.1 to 87.6
Percentage of Participants Gaining ≥5 Letters in BCVA From Baseline in the Study Eye Over Time, Treatment-Naive Population Week 56	84.0 Percentage of participants Interval 78.9 to 89.2	81.2 Percentage of participants Interval 75.9 to 86.4	81.9 Percentage of participants Interval 76.6 to 87.1
Percentage of Participants Gaining ≥5 Letters in BCVA From Baseline in the Study Eye Over Time, Treatment-Naive Population Week 96	82.7 Percentage of participants Interval 77.1 to 88.3	76.9 Percentage of participants Interval 71.2 to 82.5	82.4 Percentage of participants Interval 76.9 to 87.8
Percentage of Participants Gaining ≥5 Letters in BCVA From Baseline in the Study Eye Over Time, Treatment-Naive Population Week 60	81.0 Percentage of participants Interval 75.5 to 86.4	80.5 Percentage of participants Interval 75.2 to 85.8	80.0 Percentage of participants Interval 74.5 to 85.5
Percentage of Participants Gaining ≥5 Letters in BCVA From Baseline in the Study Eye Over Time, Treatment-Naive Population Week 64	80.7 Percentage of participants Interval 75.1 to 86.3	80.2 Percentage of participants Interval 74.9 to 85.6	80.3 Percentage of participants Interval 74.8 to 85.7
Percentage of Participants Gaining ≥5 Letters in BCVA From Baseline in the Study Eye Over Time, Treatment-Naive Population Week 68	82.0 Percentage of participants Interval 76.5 to 87.5	78.3 Percentage of participants Interval 72.6 to 83.9	79.7 Percentage of participants Interval 74.1 to 85.2
Percentage of Participants Gaining ≥5 Letters in BCVA From Baseline in the Study Eye Over Time, Treatment-Naive Population Week 72	81.5 Percentage of participants Interval 76.0 to 87.0	77.3 Percentage of participants Interval 71.6 to 82.9	80.9 Percentage of participants Interval 75.4 to 86.5
Percentage of Participants Gaining ≥5 Letters in BCVA From Baseline in the Study Eye Over Time, Treatment-Naive Population Week 76	79.5 Percentage of participants Interval 73.7 to 85.4	78.0 Percentage of participants Interval 72.4 to 83.6	83.8 Percentage of participants Interval 78.6 to 88.9
Percentage of Participants Gaining ≥5 Letters in BCVA From Baseline in the Study Eye Over Time, Treatment-Naive Population Week 80	82.0 Percentage of participants Interval 76.3 to 87.7	80.5 Percentage of participants Interval 75.2 to 85.8	80.0 Percentage of participants Interval 74.3 to 85.7
Percentage of Participants Gaining ≥5 Letters in BCVA From Baseline in the Study Eye Over Time, Treatment-Naive Population Week 84	78.6 Percentage of participants Interval 72.6 to 84.6	83.0 Percentage of participants Interval 78.0 to 87.9	81.8 Percentage of participants Interval 76.4 to 87.3
Percentage of Participants Gaining ≥5 Letters in BCVA From Baseline in the Study Eye Over Time, Treatment-Naive Population Week 88	77.9 Percentage of participants Interval 71.8 to 83.9	80.7 Percentage of participants Interval 75.4 to 86.1	80.6 Percentage of participants Interval 74.9 to 86.2
Percentage of Participants Gaining ≥5 Letters in BCVA From Baseline in the Study Eye Over Time, Treatment-Naive Population Week 92	80.5 Percentage of participants Interval 74.8 to 86.3	82.1 Percentage of participants Interval 76.8 to 87.3	82.5 Percentage of participants Interval 77.2 to 87.9
Percentage of Participants Gaining ≥5 Letters in BCVA From Baseline in the Study Eye Over Time, Treatment-Naive Population Week 100	80.0 Percentage of participants Interval 74.3 to 85.8	78.2 Percentage of participants Interval 72.6 to 83.9	85.7 Percentage of participants Interval 80.8 to 90.7

SECONDARY outcome

Timeframe: Baseline, Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, 56, 60, 64, 68, 72, 76, 80, 84, 88, 92, 96, and 100

Population: Treatment-Naive Population: all participants randomized in the study who had not received any intravitreal anti-VEGF agents in the study eye prior to randomization. Participants were grouped according to the treatment assigned at randomization. At each timepoint, only participants with non-missing, valid assessments were included in the analysis.

Best Corrected Visual Acuity (BCVA) was measured on the Early Treatment Diabetic Retinopathy Study (ETDRS) chart at a starting distance of 4 meters. The BCVA letter score ranges from 0 to 100 (best score), and a gain in BCVA letter score from baseline indicates an improvement in visual acuity. The weighted estimates of the percentage of participants were based on the Cochran-Mantel Haenszel (CMH) weights stratified by baseline BCVA (≥64 vs. \<64 letters) and region (U.S. and Canada vs. rest of the world; Asia and rest of the world were combined). Treatment policy strategy (i.e., all observed values used) and hypothetical strategy (i.e., all values censored after the occurrence of the intercurrent event) were applied to non-COVID-19 related and COVID-19 related intercurrent events, respectively. Missing data were not imputed. Invalid BCVA values were excluded from analysis. 95% confidence interval (CI) is a rounding of 95.04% CI.

Outcome measures

Outcome measures
Measure	A: Faricimab 6 mg Q8W n=238 Participants Participants randomized to Arm A received 6 milligrams (mg) faricimab intravitreal (IVT) injections once every 4 weeks (Q4W) to Week 20, followed by 6 mg faricimab IVT injections once every 8 weeks (Q8W) to Week 96, followed by the final study visit at Week 100.	B: Faricimab 6 mg PTI n=245 Participants Participants randomized to Arm B received 6 milligrams (mg) faricimab intravitreal (IVT) injections Q4W to at least Week 12, followed by a personalized treatment interval (PTI) dosing of 6 mg faricimab IVT injections up to once every 16 weeks (Q16W) through Week 96, followed by the final study visit at Week 100.	C: Aflibercept 2 mg Q8W n=242 Participants Participants randomized to Arm C received 2 milligrams (mg) aflibercept intravitreal (IVT) injections Q4W to Week 16, followed by 2 mg aflibercept IVT injections Q8W to Week 96, followed by the final study visit at Week 100.
Percentage of Participants Gaining ≥0 Letters in BCVA From Baseline in the Study Eye Over Time, Treatment-Naive Population Week 4	86.3 Percentage of participants Interval 81.9 to 90.7	90.9 Percentage of participants Interval 87.3 to 94.5	90.2 Percentage of participants Interval 86.5 to 94.0
Percentage of Participants Gaining ≥0 Letters in BCVA From Baseline in the Study Eye Over Time, Treatment-Naive Population Week 8	91.4 Percentage of participants Interval 87.8 to 95.0	93.3 Percentage of participants Interval 90.2 to 96.5	93.1 Percentage of participants Interval 89.9 to 96.4
Percentage of Participants Gaining ≥0 Letters in BCVA From Baseline in the Study Eye Over Time, Treatment-Naive Population Week 12	93.5 Percentage of participants Interval 90.4 to 96.6	96.2 Percentage of participants Interval 93.7 to 98.6	92.8 Percentage of participants Interval 89.4 to 96.1
Percentage of Participants Gaining ≥0 Letters in BCVA From Baseline in the Study Eye Over Time, Treatment-Naive Population Week 16	91.5 Percentage of participants Interval 87.8 to 95.1	94.7 Percentage of participants Interval 91.9 to 97.6	94.5 Percentage of participants Interval 91.6 to 97.4
Percentage of Participants Gaining ≥0 Letters in BCVA From Baseline in the Study Eye Over Time, Treatment-Naive Population Week 20	94.2 Percentage of participants Interval 91.2 to 97.2	92.5 Percentage of participants Interval 89.1 to 95.9	92.1 Percentage of participants Interval 88.6 to 95.6
Percentage of Participants Gaining ≥0 Letters in BCVA From Baseline in the Study Eye Over Time, Treatment-Naive Population Week 24	94.0 Percentage of participants Interval 90.9 to 97.1	93.4 Percentage of participants Interval 90.2 to 96.6	89.0 Percentage of participants Interval 85.0 to 93.1
Percentage of Participants Gaining ≥0 Letters in BCVA From Baseline in the Study Eye Over Time, Treatment-Naive Population Week 28	90.9 Percentage of participants Interval 87.0 to 94.8	94.2 Percentage of participants Interval 91.1 to 97.2	92.6 Percentage of participants Interval 89.1 to 96.1
Percentage of Participants Gaining ≥0 Letters in BCVA From Baseline in the Study Eye Over Time, Treatment-Naive Population Week 32	92.3 Percentage of participants Interval 88.5 to 96.0	94.2 Percentage of participants Interval 91.0 to 97.3	91.4 Percentage of participants Interval 87.7 to 95.2
Percentage of Participants Gaining ≥0 Letters in BCVA From Baseline in the Study Eye Over Time, Treatment-Naive Population Week 36	93.1 Percentage of participants Interval 89.5 to 96.7	93.7 Percentage of participants Interval 90.4 to 97.0	89.4 Percentage of participants Interval 85.2 to 93.6
Percentage of Participants Gaining ≥0 Letters in BCVA From Baseline in the Study Eye Over Time, Treatment-Naive Population Week 40	91.0 Percentage of participants Interval 87.0 to 94.9	93.6 Percentage of participants Interval 90.3 to 97.0	92.5 Percentage of participants Interval 88.9 to 96.2
Percentage of Participants Gaining ≥0 Letters in BCVA From Baseline in the Study Eye Over Time, Treatment-Naive Population Week 44	91.8 Percentage of participants Interval 88.0 to 95.6	93.4 Percentage of participants Interval 90.0 to 96.7	91.6 Percentage of participants Interval 87.8 to 95.4
Percentage of Participants Gaining ≥0 Letters in BCVA From Baseline in the Study Eye Over Time, Treatment-Naive Population Week 48	95.5 Percentage of participants Interval 92.6 to 98.4	91.9 Percentage of participants Interval 88.2 to 95.6	93.1 Percentage of participants Interval 89.7 to 96.6
Percentage of Participants Gaining ≥0 Letters in BCVA From Baseline in the Study Eye Over Time, Treatment-Naive Population Week 52	89.8 Percentage of participants Interval 85.6 to 94.0	89.5 Percentage of participants Interval 85.4 to 93.6	90.9 Percentage of participants Interval 87.0 to 94.9
Percentage of Participants Gaining ≥0 Letters in BCVA From Baseline in the Study Eye Over Time, Treatment-Naive Population Week 56	91.7 Percentage of participants Interval 87.8 to 95.6	92.7 Percentage of participants Interval 89.2 to 96.3	90.9 Percentage of participants Interval 86.9 to 94.9
Percentage of Participants Gaining ≥0 Letters in BCVA From Baseline in the Study Eye Over Time, Treatment-Naive Population Week 60	89.9 Percentage of participants Interval 85.7 to 94.1	93.5 Percentage of participants Interval 90.1 to 96.9	91.9 Percentage of participants Interval 88.2 to 95.7
Percentage of Participants Gaining ≥0 Letters in BCVA From Baseline in the Study Eye Over Time, Treatment-Naive Population Week 64	92.0 Percentage of participants Interval 88.1 to 95.9	92.6 Percentage of participants Interval 89.1 to 96.1	92.4 Percentage of participants Interval 88.7 to 96.1
Percentage of Participants Gaining ≥0 Letters in BCVA From Baseline in the Study Eye Over Time, Treatment-Naive Population Week 68	92.0 Percentage of participants Interval 88.1 to 95.8	93.4 Percentage of participants Interval 90.0 to 96.8	91.8 Percentage of participants Interval 88.0 to 95.6
Percentage of Participants Gaining ≥0 Letters in BCVA From Baseline in the Study Eye Over Time, Treatment-Naive Population Week 72	88.7 Percentage of participants Interval 84.1 to 93.2	92.0 Percentage of participants Interval 88.4 to 95.6	89.3 Percentage of participants Interval 84.9 to 93.7
Percentage of Participants Gaining ≥0 Letters in BCVA From Baseline in the Study Eye Over Time, Treatment-Naive Population Week 76	86.8 Percentage of participants Interval 81.8 to 91.7	90.8 Percentage of participants Interval 86.8 to 94.8	91.6 Percentage of participants Interval 87.8 to 95.5
Percentage of Participants Gaining ≥0 Letters in BCVA From Baseline in the Study Eye Over Time, Treatment-Naive Population Week 80	89.5 Percentage of participants Interval 85.0 to 94.0	90.7 Percentage of participants Interval 86.7 to 94.7	90.1 Percentage of participants Interval 85.8 to 94.3
Percentage of Participants Gaining ≥0 Letters in BCVA From Baseline in the Study Eye Over Time, Treatment-Naive Population Week 84	87.4 Percentage of participants Interval 82.6 to 92.3	92.2 Percentage of participants Interval 88.5 to 95.8	92.5 Percentage of participants Interval 88.9 to 96.1
Percentage of Participants Gaining ≥0 Letters in BCVA From Baseline in the Study Eye Over Time, Treatment-Naive Population Week 88	85.6 Percentage of participants Interval 80.4 to 90.7	88.8 Percentage of participants Interval 84.5 to 93.2	89.2 Percentage of participants Interval 84.7 to 93.7
Percentage of Participants Gaining ≥0 Letters in BCVA From Baseline in the Study Eye Over Time, Treatment-Naive Population Week 92	88.8 Percentage of participants Interval 84.2 to 93.4	90.5 Percentage of participants Interval 86.5 to 94.6	91.0 Percentage of participants Interval 86.9 to 95.1
Percentage of Participants Gaining ≥0 Letters in BCVA From Baseline in the Study Eye Over Time, Treatment-Naive Population Week 96	90.1 Percentage of participants Interval 85.7 to 94.6	87.2 Percentage of participants Interval 82.6 to 91.7	90.3 Percentage of participants Interval 86.1 to 94.6
Percentage of Participants Gaining ≥0 Letters in BCVA From Baseline in the Study Eye Over Time, Treatment-Naive Population Week 100	87.8 Percentage of participants Interval 83.1 to 92.6	86.1 Percentage of participants Interval 81.4 to 90.8	92.0 Percentage of participants Interval 88.1 to 95.9

SECONDARY outcome

Timeframe: Baseline, average of Weeks 48, 52, and 56

Best Corrected Visual Acuity (BCVA) was measured on the Early Treatment Diabetic Retinopathy Study (ETDRS) chart at a starting distance of 4 meters. For each participant, an average BCVA value was calculated across the three visits, and this averaged value was then used to determine if the endpoint was met. The results were summarized as the percentage of participants per treatment arm who met the endpoint. The weighted estimates of the percentage of participants were based on the Cochran-Mantel Haenszel (CMH) weights stratified by baseline BCVA (≥64 vs. \<64 letters), prior IVT anti-VEGF therapy (yes vs. no), and region (U.S. and Canada vs. rest of the world; Asia and rest of the world were combined). Treatment policy strategy and hypothetical strategy were applied to non-COVID-19 related and COVID-19 related intercurrent events, respectively. Missing data were not imputed. Invalid BCVA values were excluded. 95% confidence interval (CI) is a rounding of 95.04% CI.

Outcome measures

Outcome measures
Measure	A: Faricimab 6 mg Q8W n=271 Participants Participants randomized to Arm A received 6 milligrams (mg) faricimab intravitreal (IVT) injections once every 4 weeks (Q4W) to Week 20, followed by 6 mg faricimab IVT injections once every 8 weeks (Q8W) to Week 96, followed by the final study visit at Week 100.	B: Faricimab 6 mg PTI n=276 Participants Participants randomized to Arm B received 6 milligrams (mg) faricimab intravitreal (IVT) injections Q4W to at least Week 12, followed by a personalized treatment interval (PTI) dosing of 6 mg faricimab IVT injections up to once every 16 weeks (Q16W) through Week 96, followed by the final study visit at Week 100.	C: Aflibercept 2 mg Q8W n=276 Participants Participants randomized to Arm C received 2 milligrams (mg) aflibercept intravitreal (IVT) injections Q4W to Week 16, followed by 2 mg aflibercept IVT injections Q8W to Week 96, followed by the final study visit at Week 100.
Percentage of Participants Avoiding a Loss of ≥15, ≥10, or ≥5 Letters in BCVA From Baseline in the Study Eye Averaged Over Weeks 48, 52, and 56, ITT Population Avoiding a Loss of ≥15 Letters	98.1 Percentage of participants Interval 96.5 to 99.7	98.6 Percentage of participants Interval 97.2 to 100.0	98.9 Percentage of participants Interval 97.6 to 100.0
Percentage of Participants Avoiding a Loss of ≥15, ≥10, or ≥5 Letters in BCVA From Baseline in the Study Eye Averaged Over Weeks 48, 52, and 56, ITT Population Avoiding a Loss of ≥10 Letters	96.3 Percentage of participants Interval 94.1 to 98.5	98.2 Percentage of participants Interval 96.6 to 99.8	98.1 Percentage of participants Interval 96.5 to 99.7
Percentage of Participants Avoiding a Loss of ≥15, ≥10, or ≥5 Letters in BCVA From Baseline in the Study Eye Averaged Over Weeks 48, 52, and 56, ITT Population Avoiding a Loss of ≥5 Letters	95.2 Percentage of participants Interval 92.7 to 97.7	96.7 Percentage of participants Interval 94.7 to 98.8	96.3 Percentage of participants Interval 94.1 to 98.5

SECONDARY outcome

Timeframe: Baseline, Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, 56, 60, 64, 68, 72, 76, 80, 84, 88, 92, 96, and 100

Best Corrected Visual Acuity (BCVA) was measured on the Early Treatment Diabetic Retinopathy Study (ETDRS) chart at a starting distance of 4 meters. The weighted estimates of the percentage of participants avoiding a loss of letters in BCVA from baseline were based on the Cochran-Mantel Haenszel (CMH) weights stratified by baseline BCVA (≥64 vs. \<64 letters), prior IVT anti-VEGF therapy (yes vs. no), and region (U.S. and Canada vs. rest of the world; Asia and rest of the world were combined). Treatment policy strategy (i.e., all observed values used) and hypothetical strategy (i.e., all values censored after the occurrence of the intercurrent event) were applied to non-COVID-19 related and COVID-19 related intercurrent events, respectively. Missing data were not imputed. Invalid BCVA values were excluded from analysis. 95% confidence interval (CI) is a rounding of 95.04% CI.

Outcome measures

Outcome measures
Measure	A: Faricimab 6 mg Q8W n=315 Participants Participants randomized to Arm A received 6 milligrams (mg) faricimab intravitreal (IVT) injections once every 4 weeks (Q4W) to Week 20, followed by 6 mg faricimab IVT injections once every 8 weeks (Q8W) to Week 96, followed by the final study visit at Week 100.	B: Faricimab 6 mg PTI n=313 Participants Participants randomized to Arm B received 6 milligrams (mg) faricimab intravitreal (IVT) injections Q4W to at least Week 12, followed by a personalized treatment interval (PTI) dosing of 6 mg faricimab IVT injections up to once every 16 weeks (Q16W) through Week 96, followed by the final study visit at Week 100.	C: Aflibercept 2 mg Q8W n=312 Participants Participants randomized to Arm C received 2 milligrams (mg) aflibercept intravitreal (IVT) injections Q4W to Week 16, followed by 2 mg aflibercept IVT injections Q8W to Week 96, followed by the final study visit at Week 100.
Percentage of Participants Avoiding a Loss of ≥15 Letters in BCVA From Baseline in the Study Eye Over Time, ITT Population Week 40	98.8 Percentage of participants Interval 97.5 to 100.0	99.3 Percentage of participants Interval 98.2 to 100.0	99.6 Percentage of participants Interval 98.8 to 100.0
Percentage of Participants Avoiding a Loss of ≥15 Letters in BCVA From Baseline in the Study Eye Over Time, ITT Population Week 44	98.8 Percentage of participants Interval 97.5 to 100.0	98.9 Percentage of participants Interval 97.7 to 100.0	100.0 Percentage of participants Interval 100.0 to 100.0
Percentage of Participants Avoiding a Loss of ≥15 Letters in BCVA From Baseline in the Study Eye Over Time, ITT Population Week 80	97.6 Percentage of participants Interval 95.7 to 99.5	96.9 Percentage of participants Interval 94.8 to 99.0	99.1 Percentage of participants Interval 98.0 to 100.0
Percentage of Participants Avoiding a Loss of ≥15 Letters in BCVA From Baseline in the Study Eye Over Time, ITT Population Week 48	98.4 Percentage of participants Interval 96.9 to 100.0	98.1 Percentage of participants Interval 96.5 to 99.7	99.3 Percentage of participants Interval 98.3 to 100.0
Percentage of Participants Avoiding a Loss of ≥15 Letters in BCVA From Baseline in the Study Eye Over Time, ITT Population Week 4	100.0 Percentage of participants Interval 100.0 to 100.0	100.0 Percentage of participants Interval 100.0 to 100.0	100.0 Percentage of participants Interval 100.0 to 100.0
Percentage of Participants Avoiding a Loss of ≥15 Letters in BCVA From Baseline in the Study Eye Over Time, ITT Population Week 8	99.7 Percentage of participants Interval 99.0 to 100.0	100.0 Percentage of participants Interval 100.0 to 100.0	99.3 Percentage of participants Interval 98.4 to 100.0
Percentage of Participants Avoiding a Loss of ≥15 Letters in BCVA From Baseline in the Study Eye Over Time, ITT Population Week 12	99.3 Percentage of participants Interval 98.5 to 100.0	100.0 Percentage of participants Interval 100.0 to 100.0	99.7 Percentage of participants Interval 99.0 to 100.0
Percentage of Participants Avoiding a Loss of ≥15 Letters in BCVA From Baseline in the Study Eye Over Time, ITT Population Week 16	99.7 Percentage of participants Interval 99.0 to 100.0	100.0 Percentage of participants Interval 100.0 to 100.0	100.0 Percentage of participants Interval 100.0 to 100.0
Percentage of Participants Avoiding a Loss of ≥15 Letters in BCVA From Baseline in the Study Eye Over Time, ITT Population Week 20	99.3 Percentage of participants Interval 98.4 to 100.0	99.3 Percentage of participants Interval 98.4 to 100.0	99.6 Percentage of participants Interval 99.0 to 100.0
Percentage of Participants Avoiding a Loss of ≥15 Letters in BCVA From Baseline in the Study Eye Over Time, ITT Population Week 24	99.6 Percentage of participants Interval 98.9 to 100.0	100.0 Percentage of participants Interval 100.0 to 100.0	100.0 Percentage of participants Interval 100.0 to 100.0
Percentage of Participants Avoiding a Loss of ≥15 Letters in BCVA From Baseline in the Study Eye Over Time, ITT Population Week 28	99.3 Percentage of participants Interval 98.2 to 100.0	99.7 Percentage of participants Interval 99.0 to 100.0	99.6 Percentage of participants Interval 99.0 to 100.0
Percentage of Participants Avoiding a Loss of ≥15 Letters in BCVA From Baseline in the Study Eye Over Time, ITT Population Week 32	99.6 Percentage of participants Interval 98.8 to 100.0	100.0 Percentage of participants Interval 100.0 to 100.0	99.3 Percentage of participants Interval 98.3 to 100.0
Percentage of Participants Avoiding a Loss of ≥15 Letters in BCVA From Baseline in the Study Eye Over Time, ITT Population Week 84	97.1 Percentage of participants Interval 95.0 to 99.2	98.1 Percentage of participants Interval 96.5 to 99.7	99.1 Percentage of participants Interval 98.0 to 100.0
Percentage of Participants Avoiding a Loss of ≥15 Letters in BCVA From Baseline in the Study Eye Over Time, ITT Population Week 88	97.1 Percentage of participants Interval 95.0 to 99.2	97.2 Percentage of participants Interval 95.2 to 99.2	97.9 Percentage of participants Interval 96.1 to 99.7
Percentage of Participants Avoiding a Loss of ≥15 Letters in BCVA From Baseline in the Study Eye Over Time, ITT Population Week 92	97.1 Percentage of participants Interval 95.0 to 99.2	97.4 Percentage of participants Interval 95.5 to 99.3	98.3 Percentage of participants Interval 96.6 to 99.9
Percentage of Participants Avoiding a Loss of ≥15 Letters in BCVA From Baseline in the Study Eye Over Time, ITT Population Week 96	97.4 Percentage of participants Interval 95.3 to 99.4	96.6 Percentage of participants Interval 94.4 to 98.8	97.8 Percentage of participants Interval 95.9 to 99.7
Percentage of Participants Avoiding a Loss of ≥15 Letters in BCVA From Baseline in the Study Eye Over Time, ITT Population Week 100	96.3 Percentage of participants Interval 93.9 to 98.7	97.0 Percentage of participants Interval 94.9 to 99.0	98.4 Percentage of participants Interval 96.8 to 99.9
Percentage of Participants Avoiding a Loss of ≥15 Letters in BCVA From Baseline in the Study Eye Over Time, ITT Population Week 36	99.2 Percentage of participants Interval 98.0 to 100.0	99.2 Percentage of participants Interval 98.2 to 100.0	99.6 Percentage of participants Interval 98.8 to 100.0
Percentage of Participants Avoiding a Loss of ≥15 Letters in BCVA From Baseline in the Study Eye Over Time, ITT Population Week 52	97.2 Percentage of participants Interval 95.2 to 99.2	98.1 Percentage of participants Interval 96.5 to 99.7	98.4 Percentage of participants Interval 96.8 to 99.9
Percentage of Participants Avoiding a Loss of ≥15 Letters in BCVA From Baseline in the Study Eye Over Time, ITT Population Week 56	98.4 Percentage of participants Interval 96.9 to 99.9	98.5 Percentage of participants Interval 97.0 to 100.0	98.4 Percentage of participants Interval 96.9 to 99.9
Percentage of Participants Avoiding a Loss of ≥15 Letters in BCVA From Baseline in the Study Eye Over Time, ITT Population Week 60	98.1 Percentage of participants Interval 96.4 to 99.7	98.5 Percentage of participants Interval 97.0 to 99.9	99.2 Percentage of participants Interval 98.1 to 100.0
Percentage of Participants Avoiding a Loss of ≥15 Letters in BCVA From Baseline in the Study Eye Over Time, ITT Population Week 64	98.8 Percentage of participants Interval 97.4 to 100.0	97.7 Percentage of participants Interval 95.8 to 99.5	98.8 Percentage of participants Interval 97.5 to 100.0
Percentage of Participants Avoiding a Loss of ≥15 Letters in BCVA From Baseline in the Study Eye Over Time, ITT Population Week 68	99.1 Percentage of participants Interval 98.0 to 100.0	98.0 Percentage of participants Interval 96.3 to 99.7	98.8 Percentage of participants Interval 97.5 to 100.0
Percentage of Participants Avoiding a Loss of ≥15 Letters in BCVA From Baseline in the Study Eye Over Time, ITT Population Week 72	97.2 Percentage of participants Interval 95.1 to 99.2	98.8 Percentage of participants Interval 97.5 to 100.0	98.8 Percentage of participants Interval 97.5 to 100.0
Percentage of Participants Avoiding a Loss of ≥15 Letters in BCVA From Baseline in the Study Eye Over Time, ITT Population Week 76	96.6 Percentage of participants Interval 94.4 to 98.9	98.0 Percentage of participants Interval 96.3 to 99.7	98.0 Percentage of participants Interval 96.3 to 99.7

SECONDARY outcome

Timeframe: Baseline, Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, 56, 60, 64, 68, 72, 76, 80, 84, 88, 92, 96, and 100

Outcome measures

Outcome measures
Measure	A: Faricimab 6 mg Q8W n=315 Participants Participants randomized to Arm A received 6 milligrams (mg) faricimab intravitreal (IVT) injections once every 4 weeks (Q4W) to Week 20, followed by 6 mg faricimab IVT injections once every 8 weeks (Q8W) to Week 96, followed by the final study visit at Week 100.	B: Faricimab 6 mg PTI n=313 Participants Participants randomized to Arm B received 6 milligrams (mg) faricimab intravitreal (IVT) injections Q4W to at least Week 12, followed by a personalized treatment interval (PTI) dosing of 6 mg faricimab IVT injections up to once every 16 weeks (Q16W) through Week 96, followed by the final study visit at Week 100.	C: Aflibercept 2 mg Q8W n=312 Participants Participants randomized to Arm C received 2 milligrams (mg) aflibercept intravitreal (IVT) injections Q4W to Week 16, followed by 2 mg aflibercept IVT injections Q8W to Week 96, followed by the final study visit at Week 100.
Percentage of Participants Avoiding a Loss of ≥10 Letters in BCVA From Baseline in the Study Eye Over Time, ITT Population Week 52	95.3 Percentage of participants Interval 92.8 to 97.9	97.0 Percentage of participants Interval 95.0 to 99.0	96.8 Percentage of participants Interval 94.6 to 99.0
Percentage of Participants Avoiding a Loss of ≥10 Letters in BCVA From Baseline in the Study Eye Over Time, ITT Population Week 56	97.2 Percentage of participants Interval 95.2 to 99.2	98.1 Percentage of participants Interval 96.5 to 99.7	96.5 Percentage of participants Interval 94.3 to 98.7
Percentage of Participants Avoiding a Loss of ≥10 Letters in BCVA From Baseline in the Study Eye Over Time, ITT Population Week 60	96.9 Percentage of participants Interval 94.8 to 99.0	97.3 Percentage of participants Interval 95.4 to 99.3	98.1 Percentage of participants Interval 96.4 to 99.7
Percentage of Participants Avoiding a Loss of ≥10 Letters in BCVA From Baseline in the Study Eye Over Time, ITT Population Week 64	98.0 Percentage of participants Interval 96.3 to 99.7	96.5 Percentage of participants Interval 94.2 to 98.7	98.1 Percentage of participants Interval 96.4 to 99.7
Percentage of Participants Avoiding a Loss of ≥10 Letters in BCVA From Baseline in the Study Eye Over Time, ITT Population Week 68	96.9 Percentage of participants Interval 94.7 to 99.0	97.6 Percentage of participants Interval 95.8 to 99.5	98.4 Percentage of participants Interval 96.9 to 100.0
Percentage of Participants Avoiding a Loss of ≥10 Letters in BCVA From Baseline in the Study Eye Over Time, ITT Population Week 72	96.0 Percentage of participants Interval 93.6 to 98.4	98.0 Percentage of participants Interval 96.4 to 99.7	97.6 Percentage of participants Interval 95.7 to 99.5
Percentage of Participants Avoiding a Loss of ≥10 Letters in BCVA From Baseline in the Study Eye Over Time, ITT Population Week 76	95.9 Percentage of participants Interval 93.4 to 98.4	95.6 Percentage of participants Interval 93.1 to 98.1	97.6 Percentage of participants Interval 95.7 to 99.5
Percentage of Participants Avoiding a Loss of ≥10 Letters in BCVA From Baseline in the Study Eye Over Time, ITT Population Week 80	96.3 Percentage of participants Interval 94.0 to 98.7	96.2 Percentage of participants Interval 93.8 to 98.5	97.6 Percentage of participants Interval 95.9 to 99.5
Percentage of Participants Avoiding a Loss of ≥10 Letters in BCVA From Baseline in the Study Eye Over Time, ITT Population Week 84	95.5 Percentage of participants Interval 93.0 to 98.1	97.0 Percentage of participants Interval 95.0 to 99.0	99.1 Percentage of participants Interval 98.0 to 100.0
Percentage of Participants Avoiding a Loss of ≥10 Letters in BCVA From Baseline in the Study Eye Over Time, ITT Population Week 88	95.0 Percentage of participants Interval 92.3 to 97.7	95.6 Percentage of participants Interval 93.1 to 98.1	96.7 Percentage of participants Interval 94.5 to 98.9
Percentage of Participants Avoiding a Loss of ≥10 Letters in BCVA From Baseline in the Study Eye Over Time, ITT Population Week 92	95.9 Percentage of participants Interval 93.3 to 98.4	96.5 Percentage of participants Interval 94.3 to 98.7	97.5 Percentage of participants Interval 95.5 to 99.5
Percentage of Participants Avoiding a Loss of ≥10 Letters in BCVA From Baseline in the Study Eye Over Time, ITT Population Week 96	96.9 Percentage of participants Interval 94.7 to 99.2	94.3 Percentage of participants Interval 91.5 to 97.1	96.6 Percentage of participants Interval 94.3 to 98.9
Percentage of Participants Avoiding a Loss of ≥10 Letters in BCVA From Baseline in the Study Eye Over Time, ITT Population Week 100	94.3 Percentage of participants Interval 91.5 to 97.2	94.6 Percentage of participants Interval 91.8 to 97.3	97.1 Percentage of participants Interval 95.1 to 99.2
Percentage of Participants Avoiding a Loss of ≥10 Letters in BCVA From Baseline in the Study Eye Over Time, ITT Population Week 4	98.7 Percentage of participants Interval 97.5 to 99.9	100.0 Percentage of participants Interval 100.0 to 100.0	99.4 Percentage of participants Interval 98.5 to 100.0
Percentage of Participants Avoiding a Loss of ≥10 Letters in BCVA From Baseline in the Study Eye Over Time, ITT Population Week 8	98.4 Percentage of participants Interval 97.0 to 99.8	100.0 Percentage of participants Interval 100.0 to 100.0	99.0 Percentage of participants Interval 97.9 to 100.0
Percentage of Participants Avoiding a Loss of ≥10 Letters in BCVA From Baseline in the Study Eye Over Time, ITT Population Week 12	98.7 Percentage of participants Interval 97.4 to 100.0	100.0 Percentage of participants Interval 100.0 to 100.0	99.3 Percentage of participants Interval 98.4 to 100.0
Percentage of Participants Avoiding a Loss of ≥10 Letters in BCVA From Baseline in the Study Eye Over Time, ITT Population Week 16	99.3 Percentage of participants Interval 98.4 to 100.0	99.3 Percentage of participants Interval 98.4 to 100.0	99.7 Percentage of participants Interval 99.0 to 100.0
Percentage of Participants Avoiding a Loss of ≥10 Letters in BCVA From Baseline in the Study Eye Over Time, ITT Population Week 20	99.0 Percentage of participants Interval 97.8 to 100.0	98.6 Percentage of participants Interval 97.3 to 100.0	99.3 Percentage of participants Interval 98.4 to 100.0
Percentage of Participants Avoiding a Loss of ≥10 Letters in BCVA From Baseline in the Study Eye Over Time, ITT Population Week 24	98.6 Percentage of participants Interval 97.2 to 100.0	99.7 Percentage of participants Interval 99.0 to 100.0	99.3 Percentage of participants Interval 98.4 to 100.0
Percentage of Participants Avoiding a Loss of ≥10 Letters in BCVA From Baseline in the Study Eye Over Time, ITT Population Week 28	97.4 Percentage of participants Interval 95.6 to 99.3	99.0 Percentage of participants Interval 97.8 to 100.0	98.6 Percentage of participants Interval 97.2 to 100.0
Percentage of Participants Avoiding a Loss of ≥10 Letters in BCVA From Baseline in the Study Eye Over Time, ITT Population Week 32	99.2 Percentage of participants Interval 98.1 to 100.0	98.5 Percentage of participants Interval 97.0 to 99.9	98.5 Percentage of participants Interval 97.1 to 99.9
Percentage of Participants Avoiding a Loss of ≥10 Letters in BCVA From Baseline in the Study Eye Over Time, ITT Population Week 36	98.4 Percentage of participants Interval 96.9 to 99.9	98.9 Percentage of participants Interval 97.6 to 100.0	99.2 Percentage of participants Interval 98.2 to 100.0
Percentage of Participants Avoiding a Loss of ≥10 Letters in BCVA From Baseline in the Study Eye Over Time, ITT Population Week 40	97.7 Percentage of participants Interval 95.9 to 99.5	99.3 Percentage of participants Interval 98.2 to 100.0	98.5 Percentage of participants Interval 97.0 to 99.9
Percentage of Participants Avoiding a Loss of ≥10 Letters in BCVA From Baseline in the Study Eye Over Time, ITT Population Week 44	97.3 Percentage of participants Interval 95.4 to 99.3	98.2 Percentage of participants Interval 96.6 to 99.8	99.2 Percentage of participants Interval 98.2 to 100.0
Percentage of Participants Avoiding a Loss of ≥10 Letters in BCVA From Baseline in the Study Eye Over Time, ITT Population Week 48	98.1 Percentage of participants Interval 96.4 to 99.7	97.8 Percentage of participants Interval 96.0 to 99.5	98.5 Percentage of participants Interval 97.1 to 99.9

SECONDARY outcome

Timeframe: Baseline, Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, 56, 60, 64, 68, 72, 76, 80, 84, 88, 92, 96, and 100

Outcome measures

Outcome measures
Measure	A: Faricimab 6 mg Q8W n=315 Participants Participants randomized to Arm A received 6 milligrams (mg) faricimab intravitreal (IVT) injections once every 4 weeks (Q4W) to Week 20, followed by 6 mg faricimab IVT injections once every 8 weeks (Q8W) to Week 96, followed by the final study visit at Week 100.	B: Faricimab 6 mg PTI n=313 Participants Participants randomized to Arm B received 6 milligrams (mg) faricimab intravitreal (IVT) injections Q4W to at least Week 12, followed by a personalized treatment interval (PTI) dosing of 6 mg faricimab IVT injections up to once every 16 weeks (Q16W) through Week 96, followed by the final study visit at Week 100.	C: Aflibercept 2 mg Q8W n=312 Participants Participants randomized to Arm C received 2 milligrams (mg) aflibercept intravitreal (IVT) injections Q4W to Week 16, followed by 2 mg aflibercept IVT injections Q8W to Week 96, followed by the final study visit at Week 100.
Percentage of Participants Avoiding a Loss of ≥5 Letters in BCVA From Baseline in the Study Eye Over Time, ITT Population Week 4	97.7 Percentage of participants Interval 96.1 to 99.4	97.4 Percentage of participants Interval 95.6 to 99.1	96.4 Percentage of participants Interval 94.4 to 98.4
Percentage of Participants Avoiding a Loss of ≥5 Letters in BCVA From Baseline in the Study Eye Over Time, ITT Population Week 8	96.4 Percentage of participants Interval 94.4 to 98.5	98.7 Percentage of participants Interval 97.5 to 100.0	97.3 Percentage of participants Interval 95.5 to 99.1
Percentage of Participants Avoiding a Loss of ≥5 Letters in BCVA From Baseline in the Study Eye Over Time, ITT Population Week 12	98.0 Percentage of participants Interval 96.5 to 99.6	98.0 Percentage of participants Interval 96.4 to 99.6	98.4 Percentage of participants Interval 97.0 to 99.8
Percentage of Participants Avoiding a Loss of ≥5 Letters in BCVA From Baseline in the Study Eye Over Time, ITT Population Week 16	97.3 Percentage of participants Interval 95.5 to 99.1	98.6 Percentage of participants Interval 97.3 to 100.0	98.7 Percentage of participants Interval 97.4 to 100.0
Percentage of Participants Avoiding a Loss of ≥5 Letters in BCVA From Baseline in the Study Eye Over Time, ITT Population Week 20	96.9 Percentage of participants Interval 95.0 to 98.9	97.2 Percentage of participants Interval 95.4 to 99.1	97.3 Percentage of participants Interval 95.4 to 99.1
Percentage of Participants Avoiding a Loss of ≥5 Letters in BCVA From Baseline in the Study Eye Over Time, ITT Population Week 24	96.9 Percentage of participants Interval 94.9 to 98.9	96.9 Percentage of participants Interval 94.9 to 98.9	96.6 Percentage of participants Interval 94.6 to 98.7
Percentage of Participants Avoiding a Loss of ≥5 Letters in BCVA From Baseline in the Study Eye Over Time, ITT Population Week 28	96.4 Percentage of participants Interval 94.2 to 98.6	97.6 Percentage of participants Interval 95.8 to 99.3	96.1 Percentage of participants Interval 93.9 to 98.4
Percentage of Participants Avoiding a Loss of ≥5 Letters in BCVA From Baseline in the Study Eye Over Time, ITT Population Week 32	96.6 Percentage of participants Interval 94.4 to 98.8	97.4 Percentage of participants Interval 95.5 to 99.3	97.5 Percentage of participants Interval 95.6 to 99.3
Percentage of Participants Avoiding a Loss of ≥5 Letters in BCVA From Baseline in the Study Eye Over Time, ITT Population Week 36	96.2 Percentage of participants Interval 93.9 to 98.5	97.3 Percentage of participants Interval 95.4 to 99.3	97.7 Percentage of participants Interval 96.0 to 99.5
Percentage of Participants Avoiding a Loss of ≥5 Letters in BCVA From Baseline in the Study Eye Over Time, ITT Population Week 40	95.2 Percentage of participants Interval 92.6 to 97.7	95.8 Percentage of participants Interval 93.4 to 98.2	97.7 Percentage of participants Interval 95.9 to 99.5
Percentage of Participants Avoiding a Loss of ≥5 Letters in BCVA From Baseline in the Study Eye Over Time, ITT Population Week 44	95.2 Percentage of participants Interval 92.6 to 97.7	96.7 Percentage of participants Interval 94.6 to 98.8	95.8 Percentage of participants Interval 93.4 to 98.2
Percentage of Participants Avoiding a Loss of ≥5 Letters in BCVA From Baseline in the Study Eye Over Time, ITT Population Week 48	96.6 Percentage of participants Interval 94.4 to 98.8	96.7 Percentage of participants Interval 94.5 to 98.8	96.9 Percentage of participants Interval 94.9 to 99.0
Percentage of Participants Avoiding a Loss of ≥5 Letters in BCVA From Baseline in the Study Eye Over Time, ITT Population Week 52	94.2 Percentage of participants Interval 91.4 to 97.0	95.9 Percentage of participants Interval 93.5 to 98.3	94.9 Percentage of participants Interval 92.2 to 97.6
Percentage of Participants Avoiding a Loss of ≥5 Letters in BCVA From Baseline in the Study Eye Over Time, ITT Population Week 56	96.0 Percentage of participants Interval 93.7 to 98.4	96.2 Percentage of participants Interval 93.8 to 98.5	95.0 Percentage of participants Interval 92.4 to 97.6
Percentage of Participants Avoiding a Loss of ≥5 Letters in BCVA From Baseline in the Study Eye Over Time, ITT Population Week 60	94.0 Percentage of participants Interval 91.2 to 96.8	96.2 Percentage of participants Interval 93.8 to 98.5	97.0 Percentage of participants Interval 94.9 to 99.0
Percentage of Participants Avoiding a Loss of ≥5 Letters in BCVA From Baseline in the Study Eye Over Time, ITT Population Week 64	95.7 Percentage of participants Interval 93.2 to 98.2	96.1 Percentage of participants Interval 93.8 to 98.5	96.1 Percentage of participants Interval 93.8 to 98.4
Percentage of Participants Avoiding a Loss of ≥5 Letters in BCVA From Baseline in the Study Eye Over Time, ITT Population Week 68	94.8 Percentage of participants Interval 92.1 to 97.6	96.4 Percentage of participants Interval 94.1 to 98.7	96.1 Percentage of participants Interval 93.8 to 98.5
Percentage of Participants Avoiding a Loss of ≥5 Letters in BCVA From Baseline in the Study Eye Over Time, ITT Population Week 72	93.3 Percentage of participants Interval 90.3 to 96.4	95.3 Percentage of participants Interval 92.7 to 97.9	94.4 Percentage of participants Interval 91.5 to 97.2
Percentage of Participants Avoiding a Loss of ≥5 Letters in BCVA From Baseline in the Study Eye Over Time, ITT Population Week 76	92.6 Percentage of participants Interval 89.4 to 95.9	94.8 Percentage of participants Interval 92.0 to 97.5	95.2 Percentage of participants Interval 92.6 to 97.8
Percentage of Participants Avoiding a Loss of ≥5 Letters in BCVA From Baseline in the Study Eye Over Time, ITT Population Week 80	94.0 Percentage of participants Interval 91.0 to 96.9	93.4 Percentage of participants Interval 90.4 to 96.4	94.0 Percentage of participants Interval 91.1 to 96.9
Percentage of Participants Avoiding a Loss of ≥5 Letters in BCVA From Baseline in the Study Eye Over Time, ITT Population Week 84	92.8 Percentage of participants Interval 89.6 to 96.0	95.8 Percentage of participants Interval 93.4 to 98.2	97.2 Percentage of participants Interval 95.1 to 99.2
Percentage of Participants Avoiding a Loss of ≥5 Letters in BCVA From Baseline in the Study Eye Over Time, ITT Population Week 88	89.8 Percentage of participants Interval 86.0 to 93.5	92.6 Percentage of participants Interval 89.4 to 95.8	94.7 Percentage of participants Interval 91.9 to 97.5
Percentage of Participants Avoiding a Loss of ≥5 Letters in BCVA From Baseline in the Study Eye Over Time, ITT Population Week 92	93.8 Percentage of participants Interval 90.8 to 96.8	92.7 Percentage of participants Interval 89.5 to 95.8	96.7 Percentage of participants Interval 94.4 to 98.9
Percentage of Participants Avoiding a Loss of ≥5 Letters in BCVA From Baseline in the Study Eye Over Time, ITT Population Week 96	94.9 Percentage of participants Interval 92.0 to 97.7	92.3 Percentage of participants Interval 89.1 to 95.5	95.0 Percentage of participants Interval 92.3 to 97.8
Percentage of Participants Avoiding a Loss of ≥5 Letters in BCVA From Baseline in the Study Eye Over Time, ITT Population Week 100	91.1 Percentage of participants Interval 87.6 to 94.6	88.9 Percentage of participants Interval 85.1 to 92.6	96.4 Percentage of participants Interval 94.1 to 98.6

SECONDARY outcome

Timeframe: Baseline, average of Weeks 48, 52, and 56

Best Corrected Visual Acuity (BCVA) was measured on the Early Treatment Diabetic Retinopathy Study (ETDRS) chart at a starting distance of 4 meters. For each participant, an average BCVA value was calculated across the three visits, and this averaged value was then used to determine if the endpoint was met. The results were summarized as the percentage of participants per treatment arm who met the endpoint. The weighted estimates of the percentage of participants were based on the Cochran-Mantel Haenszel (CMH) weights stratified by baseline BCVA (≥64 vs. \<64 letters) and region (U.S. and Canada vs. rest of the world; Asia and rest of the world were combined). Treatment policy strategy and hypothetical strategy were applied to non-COVID-19 related and COVID-19 related intercurrent events, respectively. Missing data were not imputed. Invalid BCVA values were excluded. 95% confidence interval (CI) is a rounding of 95.04% CI.

Outcome measures

Outcome measures
Measure	A: Faricimab 6 mg Q8W n=200 Participants Participants randomized to Arm A received 6 milligrams (mg) faricimab intravitreal (IVT) injections once every 4 weeks (Q4W) to Week 20, followed by 6 mg faricimab IVT injections once every 8 weeks (Q8W) to Week 96, followed by the final study visit at Week 100.	B: Faricimab 6 mg PTI n=215 Participants Participants randomized to Arm B received 6 milligrams (mg) faricimab intravitreal (IVT) injections Q4W to at least Week 12, followed by a personalized treatment interval (PTI) dosing of 6 mg faricimab IVT injections up to once every 16 weeks (Q16W) through Week 96, followed by the final study visit at Week 100.	C: Aflibercept 2 mg Q8W n=212 Participants Participants randomized to Arm C received 2 milligrams (mg) aflibercept intravitreal (IVT) injections Q4W to Week 16, followed by 2 mg aflibercept IVT injections Q8W to Week 96, followed by the final study visit at Week 100.
Percentage of Participants Avoiding a Loss of ≥15, ≥10, or ≥5 Letters in BCVA From Baseline in the Study Eye Averaged Over Weeks 48, 52, and 56, Treatment-Naive Population Avoiding a Loss of ≥15 Letters	97.9 Percentage of participants Interval 96.0 to 99.9	98.1 Percentage of participants Interval 96.3 to 99.9	99.0 Percentage of participants Interval 97.7 to 100.0
Percentage of Participants Avoiding a Loss of ≥15, ≥10, or ≥5 Letters in BCVA From Baseline in the Study Eye Averaged Over Weeks 48, 52, and 56, Treatment-Naive Population Avoiding a Loss of ≥10 Letters	96.5 Percentage of participants Interval 93.9 to 99.0	97.7 Percentage of participants Interval 95.7 to 99.7	98.6 Percentage of participants Interval 97.0 to 100.0
Percentage of Participants Avoiding a Loss of ≥15, ≥10, or ≥5 Letters in BCVA From Baseline in the Study Eye Averaged Over Weeks 48, 52, and 56, Treatment-Naive Population Avoiding a Loss of ≥5 Letters	95.0 Percentage of participants Interval 91.9 to 98.0	95.8 Percentage of participants Interval 93.1 to 98.5	96.2 Percentage of participants Interval 93.6 to 98.8

SECONDARY outcome

Timeframe: Baseline, Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, 56, 60, 64, 68, 72, 76, 80, 84, 88, 92, 96, and 100

Population: Treatment-Naive Population: all participants randomized in the study who had not received any intravitreal anti-VEGF agents in the study eye prior to randomization. Participants were grouped according to the treatment assigned at randomization. At each timepoint, only participants with non-missing, valid assessments were included in the analysis.

Best Corrected Visual Acuity (BCVA) was measured on the Early Treatment Diabetic Retinopathy Study (ETDRS) chart at a starting distance of 4 meters. The weighted estimates of the percentage of participants avoiding a loss of letters in BCVA from baseline were based on the Cochran-Mantel Haenszel (CMH) weights stratified by baseline BCVA (≥64 vs. \<64 letters) and region (U.S. and Canada vs. rest of the world; Asia and rest of the world were combined). Treatment policy strategy (i.e., all observed values used) and hypothetical strategy (i.e., all values censored after the occurrence of the intercurrent event) were applied to non-COVID-19 related and COVID-19 related intercurrent events, respectively. Missing data were not imputed. Invalid BCVA values were excluded from analysis. 95% confidence interval (CI) is a rounding of 95.04% CI.

Outcome measures

Outcome measures
Measure	A: Faricimab 6 mg Q8W n=238 Participants Participants randomized to Arm A received 6 milligrams (mg) faricimab intravitreal (IVT) injections once every 4 weeks (Q4W) to Week 20, followed by 6 mg faricimab IVT injections once every 8 weeks (Q8W) to Week 96, followed by the final study visit at Week 100.	B: Faricimab 6 mg PTI n=245 Participants Participants randomized to Arm B received 6 milligrams (mg) faricimab intravitreal (IVT) injections Q4W to at least Week 12, followed by a personalized treatment interval (PTI) dosing of 6 mg faricimab IVT injections up to once every 16 weeks (Q16W) through Week 96, followed by the final study visit at Week 100.	C: Aflibercept 2 mg Q8W n=242 Participants Participants randomized to Arm C received 2 milligrams (mg) aflibercept intravitreal (IVT) injections Q4W to Week 16, followed by 2 mg aflibercept IVT injections Q8W to Week 96, followed by the final study visit at Week 100.
Percentage of Participants Avoiding a Loss of ≥15 Letters in BCVA From Baseline in the Study Eye Over Time, Treatment-Naive Population Week 4	100.0 Percentage of participants Interval 100.0 to 100.0	100.0 Percentage of participants Interval 100.0 to 100.0	100.0 Percentage of participants Interval 100.0 to 100.0
Percentage of Participants Avoiding a Loss of ≥15 Letters in BCVA From Baseline in the Study Eye Over Time, Treatment-Naive Population Week 8	99.6 Percentage of participants Interval 98.7 to 100.0	100.0 Percentage of participants Interval 100.0 to 100.0	99.6 Percentage of participants Interval 98.8 to 100.0
Percentage of Participants Avoiding a Loss of ≥15 Letters in BCVA From Baseline in the Study Eye Over Time, Treatment-Naive Population Week 12	99.6 Percentage of participants Interval 98.7 to 100.0	100.0 Percentage of participants Interval 100.0 to 100.0	99.6 Percentage of participants Interval 98.7 to 100.0
Percentage of Participants Avoiding a Loss of ≥15 Letters in BCVA From Baseline in the Study Eye Over Time, Treatment-Naive Population Week 16	99.6 Percentage of participants Interval 98.7 to 100.0	100.0 Percentage of participants Interval 100.0 to 100.0	100.0 Percentage of participants Interval 100.0 to 100.0
Percentage of Participants Avoiding a Loss of ≥15 Letters in BCVA From Baseline in the Study Eye Over Time, Treatment-Naive Population Week 20	99.1 Percentage of participants Interval 97.9 to 100.0	99.1 Percentage of participants Interval 97.9 to 100.0	100.0 Percentage of participants Interval 100.0 to 100.0
Percentage of Participants Avoiding a Loss of ≥15 Letters in BCVA From Baseline in the Study Eye Over Time, Treatment-Naive Population Week 24	99.5 Percentage of participants Interval 98.6 to 100.0	100.0 Percentage of participants Interval 100.0 to 100.0	100.0 Percentage of participants Interval 100.0 to 100.0
Percentage of Participants Avoiding a Loss of ≥15 Letters in BCVA From Baseline in the Study Eye Over Time, Treatment-Naive Population Week 28	99.0 Percentage of participants Interval 97.6 to 100.0	99.6 Percentage of participants Interval 98.7 to 100.0	99.5 Percentage of participants Interval 98.6 to 100.0
Percentage of Participants Avoiding a Loss of ≥15 Letters in BCVA From Baseline in the Study Eye Over Time, Treatment-Naive Population Week 32	99.5 Percentage of participants Interval 98.4 to 100.0	100.0 Percentage of participants Interval 100.0 to 100.0	99.0 Percentage of participants Interval 97.7 to 100.0
Percentage of Participants Avoiding a Loss of ≥15 Letters in BCVA From Baseline in the Study Eye Over Time, Treatment-Naive Population Week 36	98.9 Percentage of participants Interval 97.3 to 100.0	99.0 Percentage of participants Interval 97.6 to 100.0	99.5 Percentage of participants Interval 98.4 to 100.0
Percentage of Participants Avoiding a Loss of ≥15 Letters in BCVA From Baseline in the Study Eye Over Time, Treatment-Naive Population Week 40	98.4 Percentage of participants Interval 96.6 to 100.0	99.0 Percentage of participants Interval 97.7 to 100.0	99.5 Percentage of participants Interval 98.4 to 100.0
Percentage of Participants Avoiding a Loss of ≥15 Letters in BCVA From Baseline in the Study Eye Over Time, Treatment-Naive Population Week 44	98.9 Percentage of participants Interval 97.5 to 100.0	98.6 Percentage of participants Interval 97.0 to 100.0	100.0 Percentage of participants Interval 100.0 to 100.0
Percentage of Participants Avoiding a Loss of ≥15 Letters in BCVA From Baseline in the Study Eye Over Time, Treatment-Naive Population Week 48	98.4 Percentage of participants Interval 96.6 to 100.0	97.6 Percentage of participants Interval 95.5 to 99.7	99.0 Percentage of participants Interval 97.7 to 100.0
Percentage of Participants Avoiding a Loss of ≥15 Letters in BCVA From Baseline in the Study Eye Over Time, Treatment-Naive Population Week 52	96.8 Percentage of participants Interval 94.3 to 99.3	97.6 Percentage of participants Interval 95.5 to 99.7	98.4 Percentage of participants Interval 96.6 to 100.0
Percentage of Participants Avoiding a Loss of ≥15 Letters in BCVA From Baseline in the Study Eye Over Time, Treatment-Naive Population Week 56	98.4 Percentage of participants Interval 96.7 to 100.0	98.1 Percentage of participants Interval 96.2 to 99.9	98.5 Percentage of participants Interval 96.7 to 100.0
Percentage of Participants Avoiding a Loss of ≥15 Letters in BCVA From Baseline in the Study Eye Over Time, Treatment-Naive Population Week 60	97.4 Percentage of participants Interval 95.2 to 99.6	98.0 Percentage of participants Interval 96.1 to 99.9	99.0 Percentage of participants Interval 97.5 to 100.0
Percentage of Participants Avoiding a Loss of ≥15 Letters in BCVA From Baseline in the Study Eye Over Time, Treatment-Naive Population Week 64	98.4 Percentage of participants Interval 96.5 to 100.0	97.0 Percentage of participants Interval 94.6 to 99.4	98.4 Percentage of participants Interval 96.7 to 100.0
Percentage of Participants Avoiding a Loss of ≥15 Letters in BCVA From Baseline in the Study Eye Over Time, Treatment-Naive Population Week 68	98.9 Percentage of participants Interval 97.3 to 100.0	97.4 Percentage of participants Interval 95.2 to 99.6	98.4 Percentage of participants Interval 96.7 to 100.0
Percentage of Participants Avoiding a Loss of ≥15 Letters in BCVA From Baseline in the Study Eye Over Time, Treatment-Naive Population Week 72	96.2 Percentage of participants Interval 93.4 to 98.9	98.5 Percentage of participants Interval 96.8 to 100.0	98.4 Percentage of participants Interval 96.6 to 100.0
Percentage of Participants Avoiding a Loss of ≥15 Letters in BCVA From Baseline in the Study Eye Over Time, Treatment-Naive Population Week 76	95.5 Percentage of participants Interval 92.4 to 98.5	97.4 Percentage of participants Interval 95.2 to 99.6	97.9 Percentage of participants Interval 95.9 to 99.9
Percentage of Participants Avoiding a Loss of ≥15 Letters in BCVA From Baseline in the Study Eye Over Time, Treatment-Naive Population Week 80	96.7 Percentage of participants Interval 94.1 to 99.3	96.6 Percentage of participants Interval 94.1 to 99.1	98.8 Percentage of participants Interval 97.3 to 100.0
Percentage of Participants Avoiding a Loss of ≥15 Letters in BCVA From Baseline in the Study Eye Over Time, Treatment-Naive Population Week 84	96.1 Percentage of participants Interval 93.3 to 98.9	98.0 Percentage of participants Interval 96.1 to 99.9	99.5 Percentage of participants Interval 98.4 to 100.0
Percentage of Participants Avoiding a Loss of ≥15 Letters in BCVA From Baseline in the Study Eye Over Time, Treatment-Naive Population Week 88	96.1 Percentage of participants Interval 93.2 to 98.9	97.5 Percentage of participants Interval 95.3 to 99.6	97.7 Percentage of participants Interval 95.5 to 99.9
Percentage of Participants Avoiding a Loss of ≥15 Letters in BCVA From Baseline in the Study Eye Over Time, Treatment-Naive Population Week 92	96.1 Percentage of participants Interval 93.2 to 98.9	97.0 Percentage of participants Interval 94.7 to 99.3	98.3 Percentage of participants Interval 96.4 to 100.0
Percentage of Participants Avoiding a Loss of ≥15 Letters in BCVA From Baseline in the Study Eye Over Time, Treatment-Naive Population Week 96	97.1 Percentage of participants Interval 94.6 to 99.6	96.1 Percentage of participants Interval 93.4 to 98.7	98.9 Percentage of participants Interval 97.3 to 100.0
Percentage of Participants Avoiding a Loss of ≥15 Letters in BCVA From Baseline in the Study Eye Over Time, Treatment-Naive Population Week 100	96.1 Percentage of participants Interval 93.3 to 98.9	97.1 Percentage of participants Interval 94.8 to 99.4	98.4 Percentage of participants Interval 96.6 to 100.0

SECONDARY outcome

Timeframe: Baseline, Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, 56, 60, 64, 68, 72, 76, 80, 84, 88, 92, 96, and 100

Population: Treatment-Naive Population: all participants randomized in the study who had not received any intravitreal anti-VEGF agents in the study eye prior to randomization. Participants were grouped according to the treatment assigned at randomization. At each timepoint, only participants with non-missing, valid assessments were included in the analysis.

Best Corrected Visual Acuity (BCVA) was measured on the Early Treatment Diabetic Retinopathy Study (ETDRS) chart at a starting distance of 4 meters. The weighted estimates of the percentage of participants avoiding a loss of letters in BCVA from baseline were based on the Cochran-Mantel Haenszel (CMH) weights stratified by baseline BCVA (≥64 vs. \<64 letters) and region (U.S. and Canada vs. rest of the world; Asia and rest of the world were combined). Treatment policy strategy (i.e., all observed values used) and hypothetical strategy (i.e., all values censored after the occurrence of the intercurrent event) were applied to non-COVID-19 related and COVID-19 related intercurrent events, respectively. Missing data were not imputed. Invalid BCVA values were excluded from analysis. 95% confidence interval (CI) is a rounding of 95.04% CI.

Outcome measures

Outcome measures
Measure	A: Faricimab 6 mg Q8W n=238 Participants Participants randomized to Arm A received 6 milligrams (mg) faricimab intravitreal (IVT) injections once every 4 weeks (Q4W) to Week 20, followed by 6 mg faricimab IVT injections once every 8 weeks (Q8W) to Week 96, followed by the final study visit at Week 100.	B: Faricimab 6 mg PTI n=245 Participants Participants randomized to Arm B received 6 milligrams (mg) faricimab intravitreal (IVT) injections Q4W to at least Week 12, followed by a personalized treatment interval (PTI) dosing of 6 mg faricimab IVT injections up to once every 16 weeks (Q16W) through Week 96, followed by the final study visit at Week 100.	C: Aflibercept 2 mg Q8W n=242 Participants Participants randomized to Arm C received 2 milligrams (mg) aflibercept intravitreal (IVT) injections Q4W to Week 16, followed by 2 mg aflibercept IVT injections Q8W to Week 96, followed by the final study visit at Week 100.
Percentage of Participants Avoiding a Loss of ≥10 Letters in BCVA From Baseline in the Study Eye Over Time, Treatment-Naive Population Week 4	99.6 Percentage of participants Interval 98.7 to 100.0	100.0 Percentage of participants Interval 100.0 to 100.0	99.2 Percentage of participants Interval 98.0 to 100.0
Percentage of Participants Avoiding a Loss of ≥10 Letters in BCVA From Baseline in the Study Eye Over Time, Treatment-Naive Population Week 8	98.3 Percentage of participants Interval 96.6 to 100.0	100.0 Percentage of participants Interval 100.0 to 100.0	99.6 Percentage of participants Interval 98.8 to 100.0
Percentage of Participants Avoiding a Loss of ≥10 Letters in BCVA From Baseline in the Study Eye Over Time, Treatment-Naive Population Week 12	99.1 Percentage of participants Interval 97.9 to 100.0	100.0 Percentage of participants Interval 100.0 to 100.0	99.6 Percentage of participants Interval 98.7 to 100.0
Percentage of Participants Avoiding a Loss of ≥10 Letters in BCVA From Baseline in the Study Eye Over Time, Treatment-Naive Population Week 16	99.1 Percentage of participants Interval 97.9 to 100.0	99.1 Percentage of participants Interval 97.9 to 100.0	100.0 Percentage of participants Interval 100.0 to 100.0
Percentage of Participants Avoiding a Loss of ≥10 Letters in BCVA From Baseline in the Study Eye Over Time, Treatment-Naive Population Week 20	99.1 Percentage of participants Interval 97.9 to 100.0	98.3 Percentage of participants Interval 96.6 to 99.9	100.0 Percentage of participants Interval 100.0 to 100.0
Percentage of Participants Avoiding a Loss of ≥10 Letters in BCVA From Baseline in the Study Eye Over Time, Treatment-Naive Population Week 24	99.1 Percentage of participants Interval 97.8 to 100.0	99.6 Percentage of participants Interval 98.7 to 100.0	99.1 Percentage of participants Interval 97.9 to 100.0
Percentage of Participants Avoiding a Loss of ≥10 Letters in BCVA From Baseline in the Study Eye Over Time, Treatment-Naive Population Week 28	98.0 Percentage of participants Interval 96.1 to 99.9	98.7 Percentage of participants Interval 97.2 to 100.0	98.6 Percentage of participants Interval 97.1 to 100.0
Percentage of Participants Avoiding a Loss of ≥10 Letters in BCVA From Baseline in the Study Eye Over Time, Treatment-Naive Population Week 32	99.5 Percentage of participants Interval 98.4 to 100.0	98.0 Percentage of participants Interval 96.1 to 99.9	98.1 Percentage of participants Interval 96.2 to 99.9
Percentage of Participants Avoiding a Loss of ≥10 Letters in BCVA From Baseline in the Study Eye Over Time, Treatment-Naive Population Week 36	97.9 Percentage of participants Interval 95.8 to 99.9	98.5 Percentage of participants Interval 96.8 to 100.0	99.0 Percentage of participants Interval 97.6 to 100.0
Percentage of Participants Avoiding a Loss of ≥10 Letters in BCVA From Baseline in the Study Eye Over Time, Treatment-Naive Population Week 40	96.9 Percentage of participants Interval 94.5 to 99.3	99.0 Percentage of participants Interval 97.7 to 100.0	97.9 Percentage of participants Interval 95.9 to 99.9
Percentage of Participants Avoiding a Loss of ≥10 Letters in BCVA From Baseline in the Study Eye Over Time, Treatment-Naive Population Week 44	97.4 Percentage of participants Interval 95.2 to 99.6	97.6 Percentage of participants Interval 95.6 to 99.7	99.0 Percentage of participants Interval 97.6 to 100.0
Percentage of Participants Avoiding a Loss of ≥10 Letters in BCVA From Baseline in the Study Eye Over Time, Treatment-Naive Population Week 48	97.9 Percentage of participants Interval 95.9 to 99.9	97.1 Percentage of participants Interval 94.9 to 99.4	98.5 Percentage of participants Interval 96.9 to 100.0
Percentage of Participants Avoiding a Loss of ≥10 Letters in BCVA From Baseline in the Study Eye Over Time, Treatment-Naive Population Week 52	95.3 Percentage of participants Interval 92.3 to 98.3	96.2 Percentage of participants Interval 93.6 to 98.8	96.8 Percentage of participants Interval 94.4 to 99.3
Percentage of Participants Avoiding a Loss of ≥10 Letters in BCVA From Baseline in the Study Eye Over Time, Treatment-Naive Population Week 56	97.4 Percentage of participants Interval 95.2 to 99.6	97.6 Percentage of participants Interval 95.5 to 99.7	96.4 Percentage of participants Interval 93.9 to 99.0
Percentage of Participants Avoiding a Loss of ≥10 Letters in BCVA From Baseline in the Study Eye Over Time, Treatment-Naive Population Week 60	96.4 Percentage of participants Interval 93.8 to 99.0	96.5 Percentage of participants Interval 93.9 to 99.0	97.9 Percentage of participants Interval 95.9 to 99.9
Percentage of Participants Avoiding a Loss of ≥10 Letters in BCVA From Baseline in the Study Eye Over Time, Treatment-Naive Population Week 64	97.3 Percentage of participants Interval 95.0 to 99.6	96.5 Percentage of participants Interval 94.0 to 99.1	97.4 Percentage of participants Interval 95.2 to 99.6
Percentage of Participants Avoiding a Loss of ≥10 Letters in BCVA From Baseline in the Study Eye Over Time, Treatment-Naive Population Week 68	96.8 Percentage of participants Interval 94.3 to 99.3	96.9 Percentage of participants Interval 94.6 to 99.3	97.9 Percentage of participants Interval 95.9 to 99.9
Percentage of Participants Avoiding a Loss of ≥10 Letters in BCVA From Baseline in the Study Eye Over Time, Treatment-Naive Population Week 72	95.1 Percentage of participants Interval 92.0 to 98.2	98.0 Percentage of participants Interval 96.1 to 99.9	97.3 Percentage of participants Interval 95.0 to 99.6
Percentage of Participants Avoiding a Loss of ≥10 Letters in BCVA From Baseline in the Study Eye Over Time, Treatment-Naive Population Week 76	94.9 Percentage of participants Interval 91.7 to 98.2	94.3 Percentage of participants Interval 91.1 to 97.6	97.4 Percentage of participants Interval 95.1 to 99.6
Percentage of Participants Avoiding a Loss of ≥10 Letters in BCVA From Baseline in the Study Eye Over Time, Treatment-Naive Population Week 80	95.0 Percentage of participants Interval 91.8 to 98.2	95.6 Percentage of participants Interval 92.8 to 98.4	97.3 Percentage of participants Interval 94.9 to 99.6
Percentage of Participants Avoiding a Loss of ≥10 Letters in BCVA From Baseline in the Study Eye Over Time, Treatment-Naive Population Week 84	94.0 Percentage of participants Interval 90.5 to 97.4	97.1 Percentage of participants Interval 94.7 to 99.4	99.5 Percentage of participants Interval 98.4 to 100.0
Percentage of Participants Avoiding a Loss of ≥10 Letters in BCVA From Baseline in the Study Eye Over Time, Treatment-Naive Population Week 88	93.9 Percentage of participants Interval 90.4 to 97.4	95.4 Percentage of participants Interval 92.5 to 98.3	96.1 Percentage of participants Interval 93.3 to 98.9
Percentage of Participants Avoiding a Loss of ≥10 Letters in BCVA From Baseline in the Study Eye Over Time, Treatment-Naive Population Week 92	95.0 Percentage of participants Interval 91.8 to 98.2	96.5 Percentage of participants Interval 94.0 to 99.0	97.2 Percentage of participants Interval 94.9 to 99.6
Percentage of Participants Avoiding a Loss of ≥10 Letters in BCVA From Baseline in the Study Eye Over Time, Treatment-Naive Population Week 96	96.5 Percentage of participants Interval 93.7 to 99.3	93.6 Percentage of participants Interval 90.2 to 97.0	97.2 Percentage of participants Interval 94.8 to 99.6
Percentage of Participants Avoiding a Loss of ≥10 Letters in BCVA From Baseline in the Study Eye Over Time, Treatment-Naive Population Week 100	93.9 Percentage of participants Interval 90.4 to 97.4	94.6 Percentage of participants Interval 91.5 to 97.7	97.3 Percentage of participants Interval 94.9 to 99.6

SECONDARY outcome

Timeframe: Baseline, Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, 56, 60, 64, 68, 72, 76, 80, 84, 88, 92, 96, and 100

Population: Treatment-Naive Population: all participants randomized in the study who had not received any intravitreal anti-VEGF agents in the study eye prior to randomization. Participants were grouped according to the treatment assigned at randomization. At each timepoint, only participants with non-missing, valid assessments were included in the analysis.

Best Corrected Visual Acuity (BCVA) was measured on the Early Treatment Diabetic Retinopathy Study (ETDRS) chart at a starting distance of 4 meters. The weighted estimates of the percentage of participants avoiding a loss of letters in BCVA from baseline were based on the Cochran-Mantel Haenszel (CMH) weights stratified by baseline BCVA (≥64 vs. \<64 letters) and region (U.S. and Canada vs. rest of the world; Asia and rest of the world were combined). Treatment policy strategy (i.e., all observed values used) and hypothetical strategy (i.e., all values censored after the occurrence of the intercurrent event) were applied to non-COVID-19 related and COVID-19 related intercurrent events, respectively. Missing data were not imputed. Invalid BCVA values were excluded from analysis. 95% confidence interval (CI) is a rounding of 95.04% CI.

Outcome measures

Outcome measures
Measure	A: Faricimab 6 mg Q8W n=238 Participants Participants randomized to Arm A received 6 milligrams (mg) faricimab intravitreal (IVT) injections once every 4 weeks (Q4W) to Week 20, followed by 6 mg faricimab IVT injections once every 8 weeks (Q8W) to Week 96, followed by the final study visit at Week 100.	B: Faricimab 6 mg PTI n=245 Participants Participants randomized to Arm B received 6 milligrams (mg) faricimab intravitreal (IVT) injections Q4W to at least Week 12, followed by a personalized treatment interval (PTI) dosing of 6 mg faricimab IVT injections up to once every 16 weeks (Q16W) through Week 96, followed by the final study visit at Week 100.	C: Aflibercept 2 mg Q8W n=242 Participants Participants randomized to Arm C received 2 milligrams (mg) aflibercept intravitreal (IVT) injections Q4W to Week 16, followed by 2 mg aflibercept IVT injections Q8W to Week 96, followed by the final study visit at Week 100.
Percentage of Participants Avoiding a Loss of ≥5 Letters in BCVA From Baseline in the Study Eye Over Time, Treatment-Naive Population Week 4	98.7 Percentage of participants Interval 97.3 to 100.0	97.5 Percentage of participants Interval 95.5 to 99.5	97.0 Percentage of participants Interval 94.9 to 99.2
Percentage of Participants Avoiding a Loss of ≥5 Letters in BCVA From Baseline in the Study Eye Over Time, Treatment-Naive Population Week 8	96.5 Percentage of participants Interval 94.2 to 98.8	99.2 Percentage of participants Interval 98.1 to 100.0	98.3 Percentage of participants Interval 96.6 to 99.9
Percentage of Participants Avoiding a Loss of ≥5 Letters in BCVA From Baseline in the Study Eye Over Time, Treatment-Naive Population Week 12	98.3 Percentage of participants Interval 96.6 to 99.9	98.7 Percentage of participants Interval 97.3 to 100.0	98.7 Percentage of participants Interval 97.3 to 100.0
Percentage of Participants Avoiding a Loss of ≥5 Letters in BCVA From Baseline in the Study Eye Over Time, Treatment-Naive Population Week 16	97.8 Percentage of participants Interval 95.8 to 99.7	98.3 Percentage of participants Interval 96.6 to 99.9	98.7 Percentage of participants Interval 97.3 to 100.0
Percentage of Participants Avoiding a Loss of ≥5 Letters in BCVA From Baseline in the Study Eye Over Time, Treatment-Naive Population Week 20	97.3 Percentage of participants Interval 95.2 to 99.4	96.5 Percentage of participants Interval 94.2 to 98.9	97.8 Percentage of participants Interval 95.9 to 99.7
Percentage of Participants Avoiding a Loss of ≥5 Letters in BCVA From Baseline in the Study Eye Over Time, Treatment-Naive Population Week 24	97.7 Percentage of participants Interval 95.7 to 99.7	96.1 Percentage of participants Interval 93.5 to 98.6	96.5 Percentage of participants Interval 94.1 to 98.9
Percentage of Participants Avoiding a Loss of ≥5 Letters in BCVA From Baseline in the Study Eye Over Time, Treatment-Naive Population Week 28	96.6 Percentage of participants Interval 94.1 to 99.0	97.3 Percentage of participants Interval 95.2 to 99.4	96.8 Percentage of participants Interval 94.5 to 99.1
Percentage of Participants Avoiding a Loss of ≥5 Letters in BCVA From Baseline in the Study Eye Over Time, Treatment-Naive Population Week 32	97.4 Percentage of participants Interval 95.1 to 99.6	96.6 Percentage of participants Interval 94.1 to 99.1	97.6 Percentage of participants Interval 95.5 to 99.7
Percentage of Participants Avoiding a Loss of ≥5 Letters in BCVA From Baseline in the Study Eye Over Time, Treatment-Naive Population Week 36	96.3 Percentage of participants Interval 93.6 to 99.0	97.6 Percentage of participants Interval 95.4 to 99.7	98.1 Percentage of participants Interval 96.2 to 99.9
Percentage of Participants Avoiding a Loss of ≥5 Letters in BCVA From Baseline in the Study Eye Over Time, Treatment-Naive Population Week 40	94.5 Percentage of participants Interval 91.3 to 97.6	95.6 Percentage of participants Interval 92.7 to 98.4	96.9 Percentage of participants Interval 94.5 to 99.3
Percentage of Participants Avoiding a Loss of ≥5 Letters in BCVA From Baseline in the Study Eye Over Time, Treatment-Naive Population Week 44	95.9 Percentage of participants Interval 93.2 to 98.7	95.8 Percentage of participants Interval 93.1 to 98.5	96.5 Percentage of participants Interval 93.9 to 99.0
Percentage of Participants Avoiding a Loss of ≥5 Letters in BCVA From Baseline in the Study Eye Over Time, Treatment-Naive Population Week 48	96.4 Percentage of participants Interval 93.8 to 99.0	95.7 Percentage of participants Interval 93.0 to 98.5	97.5 Percentage of participants Interval 95.4 to 99.7
Percentage of Participants Avoiding a Loss of ≥5 Letters in BCVA From Baseline in the Study Eye Over Time, Treatment-Naive Population Week 52	94.3 Percentage of participants Interval 91.1 to 97.6	94.8 Percentage of participants Interval 91.7 to 97.8	94.4 Percentage of participants Interval 91.2 to 97.6
Percentage of Participants Avoiding a Loss of ≥5 Letters in BCVA From Baseline in the Study Eye Over Time, Treatment-Naive Population Week 56	95.8 Percentage of participants Interval 93.0 to 98.6	95.6 Percentage of participants Interval 92.9 to 98.4	94.4 Percentage of participants Interval 91.3 to 97.6
Percentage of Participants Avoiding a Loss of ≥5 Letters in BCVA From Baseline in the Study Eye Over Time, Treatment-Naive Population Week 60	94.4 Percentage of participants Interval 91.2 to 97.6	96.0 Percentage of participants Interval 93.3 to 98.7	96.9 Percentage of participants Interval 94.6 to 99.3
Percentage of Participants Avoiding a Loss of ≥5 Letters in BCVA From Baseline in the Study Eye Over Time, Treatment-Naive Population Week 64	95.2 Percentage of participants Interval 92.2 to 98.3	96.0 Percentage of participants Interval 93.3 to 98.7	95.8 Percentage of participants Interval 93.0 to 98.6
Percentage of Participants Avoiding a Loss of ≥5 Letters in BCVA From Baseline in the Study Eye Over Time, Treatment-Naive Population Week 68	94.6 Percentage of participants Interval 91.4 to 97.9	95.9 Percentage of participants Interval 93.2 to 98.7	96.4 Percentage of participants Interval 93.8 to 99.0
Percentage of Participants Avoiding a Loss of ≥5 Letters in BCVA From Baseline in the Study Eye Over Time, Treatment-Naive Population Week 72	92.6 Percentage of participants Interval 88.8 to 96.3	95.9 Percentage of participants Interval 93.2 to 98.7	94.7 Percentage of participants Interval 91.4 to 97.9
Percentage of Participants Avoiding a Loss of ≥5 Letters in BCVA From Baseline in the Study Eye Over Time, Treatment-Naive Population Week 76	91.1 Percentage of participants Interval 86.9 to 95.3	93.8 Percentage of participants Interval 90.5 to 97.2	94.7 Percentage of participants Interval 91.5 to 97.9
Percentage of Participants Avoiding a Loss of ≥5 Letters in BCVA From Baseline in the Study Eye Over Time, Treatment-Naive Population Week 80	92.8 Percentage of participants Interval 89.0 to 96.6	92.6 Percentage of participants Interval 89.1 to 96.2	94.2 Percentage of participants Interval 90.9 to 97.5
Percentage of Participants Avoiding a Loss of ≥5 Letters in BCVA From Baseline in the Study Eye Over Time, Treatment-Naive Population Week 84	91.9 Percentage of participants Interval 87.9 to 95.8	96.1 Percentage of participants Interval 93.4 to 98.7	96.9 Percentage of participants Interval 94.4 to 99.3
Percentage of Participants Avoiding a Loss of ≥5 Letters in BCVA From Baseline in the Study Eye Over Time, Treatment-Naive Population Week 88	88.3 Percentage of participants Interval 83.6 to 93.0	91.9 Percentage of participants Interval 88.1 to 95.7	93.5 Percentage of participants Interval 89.9 to 97.0
Percentage of Participants Avoiding a Loss of ≥5 Letters in BCVA From Baseline in the Study Eye Over Time, Treatment-Naive Population Week 92	92.7 Percentage of participants Interval 88.9 to 96.5	92.5 Percentage of participants Interval 88.9 to 96.2	96.7 Percentage of participants Interval 94.1 to 99.3
Percentage of Participants Avoiding a Loss of ≥5 Letters in BCVA From Baseline in the Study Eye Over Time, Treatment-Naive Population Week 96	94.8 Percentage of participants Interval 91.4 to 98.1	91.5 Percentage of participants Interval 87.7 to 95.4	95.2 Percentage of participants Interval 92.1 to 98.3
Percentage of Participants Avoiding a Loss of ≥5 Letters in BCVA From Baseline in the Study Eye Over Time, Treatment-Naive Population Week 100	90.6 Percentage of participants Interval 86.4 to 94.9	88.1 Percentage of participants Interval 83.7 to 92.5	96.8 Percentage of participants Interval 94.2 to 99.3

SECONDARY outcome

Timeframe: Baseline, average of Weeks 48, 52, and 56

Population: ITT Population and Treatment-Naive Population. Only participants with at least one non-missing, valid assessment at Weeks 48, 52, or 56 were included in the analysis.

Outcome measures

Outcome measures
Measure	A: Faricimab 6 mg Q8W n=271 Participants Participants randomized to Arm A received 6 milligrams (mg) faricimab intravitreal (IVT) injections once every 4 weeks (Q4W) to Week 20, followed by 6 mg faricimab IVT injections once every 8 weeks (Q8W) to Week 96, followed by the final study visit at Week 100.	B: Faricimab 6 mg PTI n=276 Participants Participants randomized to Arm B received 6 milligrams (mg) faricimab intravitreal (IVT) injections Q4W to at least Week 12, followed by a personalized treatment interval (PTI) dosing of 6 mg faricimab IVT injections up to once every 16 weeks (Q16W) through Week 96, followed by the final study visit at Week 100.	C: Aflibercept 2 mg Q8W n=276 Participants Participants randomized to Arm C received 2 milligrams (mg) aflibercept intravitreal (IVT) injections Q4W to Week 16, followed by 2 mg aflibercept IVT injections Q8W to Week 96, followed by the final study visit at Week 100.
Percentage of Participants Gaining ≥15 Letters in BCVA From Baseline or Achieving BCVA Snellen Equivalent of 20/20 or Better (BCVA ≥84 Letters) in the Study Eye Averaged Over Weeks 48, 52, and 56, ITT and Treatment-Naive Populations ITT Population	32.1 Percentage of participants Interval 26.6 to 37.6	39.1 Percentage of participants Interval 33.5 to 44.7	37.0 Percentage of participants Interval 31.5 to 42.5
Percentage of Participants Gaining ≥15 Letters in BCVA From Baseline or Achieving BCVA Snellen Equivalent of 20/20 or Better (BCVA ≥84 Letters) in the Study Eye Averaged Over Weeks 48, 52, and 56, ITT and Treatment-Naive Populations Treatment-Naive Population	31.5 Percentage of participants Interval 25.1 to 38.0	39.2 Percentage of participants Interval 32.8 to 45.5	40.2 Percentage of participants Interval 33.7 to 46.6

SECONDARY outcome

Timeframe: Baseline, Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, 56, 60, 64, 68, 72, 76, 80, 84, 88, 92, 96, and 100

Best Corrected Visual Acuity (BCVA) was measured on the Early Treatment Diabetic Retinopathy Study (ETDRS) chart at a starting distance of 4 meters. The BCVA letter score ranges from 0 to 100 (best score), and a gain in BCVA letter score from baseline indicates an improvement in visual acuity. The weighted estimates of the percentage of participants were based on the Cochran-Mantel Haenszel (CMH) weights stratified by baseline BCVA (≥64 vs. \<64 letters), prior IVT anti-VEGF therapy (yes vs. no), and region (U.S. and Canada vs. rest of the world; Asia and rest of the world were combined). Treatment policy strategy (i.e., all observed values used) and hypothetical strategy (i.e., all values censored after the occurrence of the intercurrent event) were applied to non-COVID-19 related and COVID-19 related intercurrent events, respectively. Missing data were not imputed. Invalid BCVA values were excluded from analysis. 95% confidence interval (CI) is a rounding of 95.04% CI.

Outcome measures

Outcome measures
Measure	A: Faricimab 6 mg Q8W n=315 Participants Participants randomized to Arm A received 6 milligrams (mg) faricimab intravitreal (IVT) injections once every 4 weeks (Q4W) to Week 20, followed by 6 mg faricimab IVT injections once every 8 weeks (Q8W) to Week 96, followed by the final study visit at Week 100.	B: Faricimab 6 mg PTI n=313 Participants Participants randomized to Arm B received 6 milligrams (mg) faricimab intravitreal (IVT) injections Q4W to at least Week 12, followed by a personalized treatment interval (PTI) dosing of 6 mg faricimab IVT injections up to once every 16 weeks (Q16W) through Week 96, followed by the final study visit at Week 100.	C: Aflibercept 2 mg Q8W n=312 Participants Participants randomized to Arm C received 2 milligrams (mg) aflibercept intravitreal (IVT) injections Q4W to Week 16, followed by 2 mg aflibercept IVT injections Q8W to Week 96, followed by the final study visit at Week 100.
Percentage of Participants Gaining ≥15 Letters in BCVA From Baseline or Achieving BCVA Snellen Equivalent of 20/20 or Better (BCVA ≥84 Letters) in the Study Eye Over Time, ITT Population Week 24	31.3 Percentage of participants Interval 26.0 to 36.5	37.8 Percentage of participants Interval 32.5 to 43.2	30.9 Percentage of participants Interval 25.7 to 36.0
Percentage of Participants Gaining ≥15 Letters in BCVA From Baseline or Achieving BCVA Snellen Equivalent of 20/20 or Better (BCVA ≥84 Letters) in the Study Eye Over Time, ITT Population Week 28	28.3 Percentage of participants Interval 23.1 to 33.5	32.6 Percentage of participants Interval 27.4 to 37.8	35.0 Percentage of participants Interval 29.7 to 40.4
Percentage of Participants Gaining ≥15 Letters in BCVA From Baseline or Achieving BCVA Snellen Equivalent of 20/20 or Better (BCVA ≥84 Letters) in the Study Eye Over Time, ITT Population Week 32	33.7 Percentage of participants Interval 28.0 to 39.3	38.8 Percentage of participants Interval 33.2 to 44.4	31.0 Percentage of participants Interval 25.8 to 36.2
Percentage of Participants Gaining ≥15 Letters in BCVA From Baseline or Achieving BCVA Snellen Equivalent of 20/20 or Better (BCVA ≥84 Letters) in the Study Eye Over Time, ITT Population Week 36	29.6 Percentage of participants Interval 24.1 to 35.0	42.4 Percentage of participants Interval 36.8 to 48.1	35.6 Percentage of participants Interval 30.0 to 41.1
Percentage of Participants Gaining ≥15 Letters in BCVA From Baseline or Achieving BCVA Snellen Equivalent of 20/20 or Better (BCVA ≥84 Letters) in the Study Eye Over Time, ITT Population Week 40	32.9 Percentage of participants Interval 27.4 to 38.5	40.4 Percentage of participants Interval 34.7 to 46.2	33.8 Percentage of participants Interval 28.2 to 39.4
Percentage of Participants Gaining ≥15 Letters in BCVA From Baseline or Achieving BCVA Snellen Equivalent of 20/20 or Better (BCVA ≥84 Letters) in the Study Eye Over Time, ITT Population Week 44	32.1 Percentage of participants Interval 26.5 to 37.7	39.7 Percentage of participants Interval 34.1 to 45.3	39.9 Percentage of participants Interval 34.2 to 45.7
Percentage of Participants Gaining ≥15 Letters in BCVA From Baseline or Achieving BCVA Snellen Equivalent of 20/20 or Better (BCVA ≥84 Letters) in the Study Eye Over Time, ITT Population Week 48	35.7 Percentage of participants Interval 30.0 to 41.5	41.8 Percentage of participants Interval 36.1 to 47.6	41.7 Percentage of participants Interval 36.0 to 47.4
Percentage of Participants Gaining ≥15 Letters in BCVA From Baseline or Achieving BCVA Snellen Equivalent of 20/20 or Better (BCVA ≥84 Letters) in the Study Eye Over Time, ITT Population Week 52	35.7 Percentage of participants Interval 29.9 to 41.4	40.2 Percentage of participants Interval 34.5 to 45.8	41.7 Percentage of participants Interval 35.8 to 47.6
Percentage of Participants Gaining ≥15 Letters in BCVA From Baseline or Achieving BCVA Snellen Equivalent of 20/20 or Better (BCVA ≥84 Letters) in the Study Eye Over Time, ITT Population Week 56	43.1 Percentage of participants Interval 37.1 to 49.1	42.6 Percentage of participants Interval 36.7 to 48.4	35.7 Percentage of participants Interval 30.1 to 41.4
Percentage of Participants Gaining ≥15 Letters in BCVA From Baseline or Achieving BCVA Snellen Equivalent of 20/20 or Better (BCVA ≥84 Letters) in the Study Eye Over Time, ITT Population Week 60	39.5 Percentage of participants Interval 33.7 to 45.3	45.0 Percentage of participants Interval 39.1 to 51.0	40.6 Percentage of participants Interval 34.8 to 46.3
Percentage of Participants Gaining ≥15 Letters in BCVA From Baseline or Achieving BCVA Snellen Equivalent of 20/20 or Better (BCVA ≥84 Letters) in the Study Eye Over Time, ITT Population Week 4	8.7 Percentage of participants Interval 5.6 to 11.8	14.6 Percentage of participants Interval 10.8 to 18.4	13.3 Percentage of participants Interval 9.6 to 17.0
Percentage of Participants Gaining ≥15 Letters in BCVA From Baseline or Achieving BCVA Snellen Equivalent of 20/20 or Better (BCVA ≥84 Letters) in the Study Eye Over Time, ITT Population Week 64	42.1 Percentage of participants Interval 36.1 to 48.1	44.0 Percentage of participants Interval 38.2 to 49.8	37.9 Percentage of participants Interval 32.1 to 43.7
Percentage of Participants Gaining ≥15 Letters in BCVA From Baseline or Achieving BCVA Snellen Equivalent of 20/20 or Better (BCVA ≥84 Letters) in the Study Eye Over Time, ITT Population Week 8	15.3 Percentage of participants Interval 11.3 to 19.3	20.1 Percentage of participants Interval 15.9 to 24.4	19.9 Percentage of participants Interval 15.6 to 24.3
Percentage of Participants Gaining ≥15 Letters in BCVA From Baseline or Achieving BCVA Snellen Equivalent of 20/20 or Better (BCVA ≥84 Letters) in the Study Eye Over Time, ITT Population Week 68	42.2 Percentage of participants Interval 36.2 to 48.2	45.6 Percentage of participants Interval 39.7 to 51.6	40.3 Percentage of participants Interval 34.5 to 46.2
Percentage of Participants Gaining ≥15 Letters in BCVA From Baseline or Achieving BCVA Snellen Equivalent of 20/20 or Better (BCVA ≥84 Letters) in the Study Eye Over Time, ITT Population Week 12	17.9 Percentage of participants Interval 13.6 to 22.1	25.7 Percentage of participants Interval 21.1 to 30.4	25.3 Percentage of participants Interval 20.6 to 30.0
Percentage of Participants Gaining ≥15 Letters in BCVA From Baseline or Achieving BCVA Snellen Equivalent of 20/20 or Better (BCVA ≥84 Letters) in the Study Eye Over Time, ITT Population Week 72	39.8 Percentage of participants Interval 33.9 to 45.8	40.5 Percentage of participants Interval 34.8 to 46.2	37.7 Percentage of participants Interval 31.8 to 43.6
Percentage of Participants Gaining ≥15 Letters in BCVA From Baseline or Achieving BCVA Snellen Equivalent of 20/20 or Better (BCVA ≥84 Letters) in the Study Eye Over Time, ITT Population Week 76	42.2 Percentage of participants Interval 36.1 to 48.4	47.7 Percentage of participants Interval 41.8 to 53.5	42.9 Percentage of participants Interval 36.8 to 49.0
Percentage of Participants Gaining ≥15 Letters in BCVA From Baseline or Achieving BCVA Snellen Equivalent of 20/20 or Better (BCVA ≥84 Letters) in the Study Eye Over Time, ITT Population Week 80	42.9 Percentage of participants Interval 36.8 to 49.0	44.8 Percentage of participants Interval 39.0 to 50.5	41.9 Percentage of participants Interval 35.9 to 47.8
Percentage of Participants Gaining ≥15 Letters in BCVA From Baseline or Achieving BCVA Snellen Equivalent of 20/20 or Better (BCVA ≥84 Letters) in the Study Eye Over Time, ITT Population Week 84	42.4 Percentage of participants Interval 36.3 to 48.5	43.0 Percentage of participants Interval 37.2 to 48.7	42.9 Percentage of participants Interval 36.9 to 48.9
Percentage of Participants Gaining ≥15 Letters in BCVA From Baseline or Achieving BCVA Snellen Equivalent of 20/20 or Better (BCVA ≥84 Letters) in the Study Eye Over Time, ITT Population Week 88	41.2 Percentage of participants Interval 35.1 to 47.3	41.7 Percentage of participants Interval 36.1 to 47.4	40.0 Percentage of participants Interval 34.1 to 46.0
Percentage of Participants Gaining ≥15 Letters in BCVA From Baseline or Achieving BCVA Snellen Equivalent of 20/20 or Better (BCVA ≥84 Letters) in the Study Eye Over Time, ITT Population Week 92	42.5 Percentage of participants Interval 36.4 to 48.5	43.6 Percentage of participants Interval 37.8 to 49.4	42.7 Percentage of participants Interval 36.7 to 48.7
Percentage of Participants Gaining ≥15 Letters in BCVA From Baseline or Achieving BCVA Snellen Equivalent of 20/20 or Better (BCVA ≥84 Letters) in the Study Eye Over Time, ITT Population Week 96	44.9 Percentage of participants Interval 38.7 to 51.1	42.4 Percentage of participants Interval 36.6 to 48.1	42.7 Percentage of participants Interval 36.6 to 48.7
Percentage of Participants Gaining ≥15 Letters in BCVA From Baseline or Achieving BCVA Snellen Equivalent of 20/20 or Better (BCVA ≥84 Letters) in the Study Eye Over Time, ITT Population Week 100	43.5 Percentage of participants Interval 37.5 to 49.6	41.8 Percentage of participants Interval 36.1 to 47.5	44.7 Percentage of participants Interval 38.6 to 50.8
Percentage of Participants Gaining ≥15 Letters in BCVA From Baseline or Achieving BCVA Snellen Equivalent of 20/20 or Better (BCVA ≥84 Letters) in the Study Eye Over Time, ITT Population Week 16	24.1 Percentage of participants Interval 19.2 to 28.9	29.1 Percentage of participants Interval 24.2 to 34.0	25.2 Percentage of participants Interval 20.5 to 30.0
Percentage of Participants Gaining ≥15 Letters in BCVA From Baseline or Achieving BCVA Snellen Equivalent of 20/20 or Better (BCVA ≥84 Letters) in the Study Eye Over Time, ITT Population Week 20	30.1 Percentage of participants Interval 24.9 to 35.2	30.8 Percentage of participants Interval 25.6 to 35.9	27.7 Percentage of participants Interval 22.8 to 32.6

SECONDARY outcome

Timeframe: Baseline, Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, 56, 60, 64, 68, 72, 76, 80, 84, 88, 92, 96, and 100

Population: Treatment-Naive Population: all participants randomized in the study who had not received any intravitreal anti-VEGF agents in the study eye prior to randomization. Participants were grouped according to the treatment assigned at randomization. At each timepoint, only participants with non-missing, valid assessments were included in the analysis.

Best Corrected Visual Acuity (BCVA) was measured on the Early Treatment Diabetic Retinopathy Study (ETDRS) chart at a starting distance of 4 meters. The BCVA letter score ranges from 0 to 100 (best score), and a gain in BCVA letter score from baseline indicates an improvement in visual acuity. The weighted estimates of the percentage of participants were based on the Cochran-Mantel Haenszel (CMH) weights stratified by baseline BCVA (≥64 vs. \<64 letters) and region (U.S. and Canada vs. rest of the world; Asia and rest of the world were combined). Treatment policy strategy (i.e., all observed values used) and hypothetical strategy (i.e., all values censored after the occurrence of the intercurrent event) were applied to non-COVID-19 related and COVID-19 related intercurrent events, respectively. Missing data were not imputed. Invalid BCVA values were excluded from analysis. 95% confidence interval (CI) is a rounding of 95.04% CI.

Outcome measures

Outcome measures
Measure	A: Faricimab 6 mg Q8W n=238 Participants Participants randomized to Arm A received 6 milligrams (mg) faricimab intravitreal (IVT) injections once every 4 weeks (Q4W) to Week 20, followed by 6 mg faricimab IVT injections once every 8 weeks (Q8W) to Week 96, followed by the final study visit at Week 100.	B: Faricimab 6 mg PTI n=245 Participants Participants randomized to Arm B received 6 milligrams (mg) faricimab intravitreal (IVT) injections Q4W to at least Week 12, followed by a personalized treatment interval (PTI) dosing of 6 mg faricimab IVT injections up to once every 16 weeks (Q16W) through Week 96, followed by the final study visit at Week 100.	C: Aflibercept 2 mg Q8W n=242 Participants Participants randomized to Arm C received 2 milligrams (mg) aflibercept intravitreal (IVT) injections Q4W to Week 16, followed by 2 mg aflibercept IVT injections Q8W to Week 96, followed by the final study visit at Week 100.
Percentage of Participants Gaining ≥15 Letters in BCVA From Baseline or Achieving BCVA Snellen Equivalent of 20/20 or Better (BCVA ≥84 Letters) in the Study Eye Over Time, Treatment-Naive Population Week 4	9.8 Percentage of participants Interval 6.0 to 13.5	17.0 Percentage of participants Interval 12.4 to 21.6	15.2 Percentage of participants Interval 10.7 to 19.8
Percentage of Participants Gaining ≥15 Letters in BCVA From Baseline or Achieving BCVA Snellen Equivalent of 20/20 or Better (BCVA ≥84 Letters) in the Study Eye Over Time, Treatment-Naive Population Week 8	16.0 Percentage of participants Interval 11.3 to 20.7	20.9 Percentage of participants Interval 16.1 to 25.7	22.2 Percentage of participants Interval 16.9 to 27.4
Percentage of Participants Gaining ≥15 Letters in BCVA From Baseline or Achieving BCVA Snellen Equivalent of 20/20 or Better (BCVA ≥84 Letters) in the Study Eye Over Time, Treatment-Naive Population Week 12	19.2 Percentage of participants Interval 14.1 to 24.2	25.6 Percentage of participants Interval 20.3 to 30.9	28.5 Percentage of participants Interval 22.9 to 34.1
Percentage of Participants Gaining ≥15 Letters in BCVA From Baseline or Achieving BCVA Snellen Equivalent of 20/20 or Better (BCVA ≥84 Letters) in the Study Eye Over Time, Treatment-Naive Population Week 16	24.9 Percentage of participants Interval 19.2 to 30.5	29.5 Percentage of participants Interval 23.8 to 35.2	27.9 Percentage of participants Interval 22.2 to 33.6
Percentage of Participants Gaining ≥15 Letters in BCVA From Baseline or Achieving BCVA Snellen Equivalent of 20/20 or Better (BCVA ≥84 Letters) in the Study Eye Over Time, Treatment-Naive Population Week 20	31.0 Percentage of participants Interval 25.0 to 37.0	30.4 Percentage of participants Interval 24.6 to 36.1	30.6 Percentage of participants Interval 24.8 to 36.4
Percentage of Participants Gaining ≥15 Letters in BCVA From Baseline or Achieving BCVA Snellen Equivalent of 20/20 or Better (BCVA ≥84 Letters) in the Study Eye Over Time, Treatment-Naive Population Week 24	32.5 Percentage of participants Interval 26.3 to 38.7	38.2 Percentage of participants Interval 32.1 to 44.3	33.3 Percentage of participants Interval 27.3 to 39.4
Percentage of Participants Gaining ≥15 Letters in BCVA From Baseline or Achieving BCVA Snellen Equivalent of 20/20 or Better (BCVA ≥84 Letters) in the Study Eye Over Time, Treatment-Naive Population Week 28	26.9 Percentage of participants Interval 20.9 to 32.9	32.0 Percentage of participants Interval 26.2 to 37.8	38.5 Percentage of participants Interval 32.2 to 44.8
Percentage of Participants Gaining ≥15 Letters in BCVA From Baseline or Achieving BCVA Snellen Equivalent of 20/20 or Better (BCVA ≥84 Letters) in the Study Eye Over Time, Treatment-Naive Population Week 32	33.3 Percentage of participants Interval 26.7 to 39.9	40.5 Percentage of participants Interval 34.0 to 46.9	35.4 Percentage of participants Interval 29.0 to 41.7
Percentage of Participants Gaining ≥15 Letters in BCVA From Baseline or Achieving BCVA Snellen Equivalent of 20/20 or Better (BCVA ≥84 Letters) in the Study Eye Over Time, Treatment-Naive Population Week 36	29.5 Percentage of participants Interval 23.1 to 36.0	44.8 Percentage of participants Interval 38.3 to 51.3	38.4 Percentage of participants Interval 31.9 to 44.8
Percentage of Participants Gaining ≥15 Letters in BCVA From Baseline or Achieving BCVA Snellen Equivalent of 20/20 or Better (BCVA ≥84 Letters) in the Study Eye Over Time, Treatment-Naive Population Week 40	31.5 Percentage of participants Interval 25.1 to 37.9	41.1 Percentage of participants Interval 34.5 to 47.7	37.1 Percentage of participants Interval 30.4 to 43.7
Percentage of Participants Gaining ≥15 Letters in BCVA From Baseline or Achieving BCVA Snellen Equivalent of 20/20 or Better (BCVA ≥84 Letters) in the Study Eye Over Time, Treatment-Naive Population Week 44	31.1 Percentage of participants Interval 24.7 to 37.6	42.9 Percentage of participants Interval 36.4 to 49.5	42.7 Percentage of participants Interval 36.0 to 49.4
Percentage of Participants Gaining ≥15 Letters in BCVA From Baseline or Achieving BCVA Snellen Equivalent of 20/20 or Better (BCVA ≥84 Letters) in the Study Eye Over Time, Treatment-Naive Population Week 48	37.5 Percentage of participants Interval 30.7 to 44.3	41.9 Percentage of participants Interval 35.3 to 48.5	44.9 Percentage of participants Interval 38.2 to 51.6
Percentage of Participants Gaining ≥15 Letters in BCVA From Baseline or Achieving BCVA Snellen Equivalent of 20/20 or Better (BCVA ≥84 Letters) in the Study Eye Over Time, Treatment-Naive Population Week 52	35.5 Percentage of participants Interval 28.9 to 42.2	39.2 Percentage of participants Interval 32.8 to 45.6	43.8 Percentage of participants Interval 36.9 to 50.6
Percentage of Participants Gaining ≥15 Letters in BCVA From Baseline or Achieving BCVA Snellen Equivalent of 20/20 or Better (BCVA ≥84 Letters) in the Study Eye Over Time, Treatment-Naive Population Week 56	43.3 Percentage of participants Interval 36.3 to 50.3	43.1 Percentage of participants Interval 36.5 to 49.7	38.9 Percentage of participants Interval 32.2 to 45.5
Percentage of Participants Gaining ≥15 Letters in BCVA From Baseline or Achieving BCVA Snellen Equivalent of 20/20 or Better (BCVA ≥84 Letters) in the Study Eye Over Time, Treatment-Naive Population Week 60	39.4 Percentage of participants Interval 32.6 to 46.2	46.7 Percentage of participants Interval 39.9 to 53.5	43.6 Percentage of participants Interval 36.8 to 50.4
Percentage of Participants Gaining ≥15 Letters in BCVA From Baseline or Achieving BCVA Snellen Equivalent of 20/20 or Better (BCVA ≥84 Letters) in the Study Eye Over Time, Treatment-Naive Population Week 64	43.0 Percentage of participants Interval 36.0 to 50.0	46.4 Percentage of participants Interval 39.8 to 53.1	38.7 Percentage of participants Interval 32.0 to 45.3
Percentage of Participants Gaining ≥15 Letters in BCVA From Baseline or Achieving BCVA Snellen Equivalent of 20/20 or Better (BCVA ≥84 Letters) in the Study Eye Over Time, Treatment-Naive Population Week 68	43.7 Percentage of participants Interval 36.6 to 50.7	47.9 Percentage of participants Interval 41.1 to 54.7	42.2 Percentage of participants Interval 35.4 to 49.0
Percentage of Participants Gaining ≥15 Letters in BCVA From Baseline or Achieving BCVA Snellen Equivalent of 20/20 or Better (BCVA ≥84 Letters) in the Study Eye Over Time, Treatment-Naive Population Week 72	40.7 Percentage of participants Interval 33.7 to 47.8	42.1 Percentage of participants Interval 35.5 to 48.7	39.3 Percentage of participants Interval 32.5 to 46.2
Percentage of Participants Gaining ≥15 Letters in BCVA From Baseline or Achieving BCVA Snellen Equivalent of 20/20 or Better (BCVA ≥84 Letters) in the Study Eye Over Time, Treatment-Naive Population Week 76	44.6 Percentage of participants Interval 37.3 to 51.8	49.9 Percentage of participants Interval 43.3 to 56.6	43.8 Percentage of participants Interval 36.8 to 50.8
Percentage of Participants Gaining ≥15 Letters in BCVA From Baseline or Achieving BCVA Snellen Equivalent of 20/20 or Better (BCVA ≥84 Letters) in the Study Eye Over Time, Treatment-Naive Population Week 80	44.6 Percentage of participants Interval 37.3 to 51.8	46.6 Percentage of participants Interval 40.1 to 53.2	46.1 Percentage of participants Interval 39.1 to 53.1
Percentage of Participants Gaining ≥15 Letters in BCVA From Baseline or Achieving BCVA Snellen Equivalent of 20/20 or Better (BCVA ≥84 Letters) in the Study Eye Over Time, Treatment-Naive Population Week 84	42.7 Percentage of participants Interval 35.6 to 49.9	45.2 Percentage of participants Interval 38.6 to 51.7	45.7 Percentage of participants Interval 38.7 to 52.7
Percentage of Participants Gaining ≥15 Letters in BCVA From Baseline or Achieving BCVA Snellen Equivalent of 20/20 or Better (BCVA ≥84 Letters) in the Study Eye Over Time, Treatment-Naive Population Week 88	41.3 Percentage of participants Interval 34.2 to 48.5	42.7 Percentage of participants Interval 36.3 to 49.2	42.5 Percentage of participants Interval 35.5 to 49.6
Percentage of Participants Gaining ≥15 Letters in BCVA From Baseline or Achieving BCVA Snellen Equivalent of 20/20 or Better (BCVA ≥84 Letters) in the Study Eye Over Time, Treatment-Naive Population Week 92	43.4 Percentage of participants Interval 36.3 to 50.6	45.5 Percentage of participants Interval 38.9 to 52.1	43.9 Percentage of participants Interval 36.9 to 50.8
Percentage of Participants Gaining ≥15 Letters in BCVA From Baseline or Achieving BCVA Snellen Equivalent of 20/20 or Better (BCVA ≥84 Letters) in the Study Eye Over Time, Treatment-Naive Population Week 96	46.7 Percentage of participants Interval 39.3 to 54.1	43.6 Percentage of participants Interval 37.2 to 50.1	44.7 Percentage of participants Interval 37.7 to 51.8
Percentage of Participants Gaining ≥15 Letters in BCVA From Baseline or Achieving BCVA Snellen Equivalent of 20/20 or Better (BCVA ≥84 Letters) in the Study Eye Over Time, Treatment-Naive Population Week 100	44.1 Percentage of participants Interval 37.0 to 51.3	44.4 Percentage of participants Interval 37.9 to 50.9	45.8 Percentage of participants Interval 38.8 to 52.9

SECONDARY outcome

Timeframe: Baseline, average of Weeks 48, 52, and 56

Population: ITT Population and Treatment-Naive Population. Only participants with at least one non-missing, valid assessment at Weeks 48, 52, or 56 were included in the analysis.

BCVA was measured on the ETDRS chart at a starting distance of 4 meters. The BCVA letter score ranges from 0 to 100 (best score), and a gain in BCVA from baseline indicates an improvement in visual acuity. For each participant, an average BCVA value was calculated across the three visits, and this averaged value was then used to determine if the endpoint was met. The results were summarized as the percentage of participants per treatment arm who met the endpoint. The weighted estimates of the percentage of participants were based on the Cochran-Mantel Haenszel (CMH) weights stratified by baseline BCVA (≥69 vs. \<69 letters), prior IVT anti-VEGF therapy (yes vs. no), and region (U.S. and Canada vs. rest of the world). Treatment policy strategy and hypothetical strategy were applied to non-COVID-19 related and COVID-19 related intercurrent events, respectively. Missing data were not imputed. Invalid BCVA values were excluded. 95% confidence interval (CI) is a rounding of 95.04% CI.

Outcome measures

Outcome measures
Measure	A: Faricimab 6 mg Q8W n=271 Participants Participants randomized to Arm A received 6 milligrams (mg) faricimab intravitreal (IVT) injections once every 4 weeks (Q4W) to Week 20, followed by 6 mg faricimab IVT injections once every 8 weeks (Q8W) to Week 96, followed by the final study visit at Week 100.	B: Faricimab 6 mg PTI n=276 Participants Participants randomized to Arm B received 6 milligrams (mg) faricimab intravitreal (IVT) injections Q4W to at least Week 12, followed by a personalized treatment interval (PTI) dosing of 6 mg faricimab IVT injections up to once every 16 weeks (Q16W) through Week 96, followed by the final study visit at Week 100.	C: Aflibercept 2 mg Q8W n=276 Participants Participants randomized to Arm C received 2 milligrams (mg) aflibercept intravitreal (IVT) injections Q4W to Week 16, followed by 2 mg aflibercept IVT injections Q8W to Week 96, followed by the final study visit at Week 100.
Percentage of Participants With BCVA Snellen Equivalent of 20/40 or Better (BCVA ≥69 Letters) in the Study Eye Averaged Over Weeks 48, 52, and 56, ITT and Treatment-Naive Populations ITT Population	71.6 Percentage of participants Interval 66.5 to 76.6	77.1 Percentage of participants Interval 72.4 to 81.8	74.8 Percentage of participants Interval 69.9 to 79.6
Percentage of Participants With BCVA Snellen Equivalent of 20/40 or Better (BCVA ≥69 Letters) in the Study Eye Averaged Over Weeks 48, 52, and 56, ITT and Treatment-Naive Populations Treatment-Naive Population	72.7 Percentage of participants Interval 66.9 to 78.5	75.7 Percentage of participants Interval 70.3 to 81.1	77.4 Percentage of participants Interval 72.2 to 82.7

SECONDARY outcome

Timeframe: Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, 56, 60, 64, 68, 72, 76, 80, 84, 88, 92, 96, and 100

Best Corrected Visual Acuity (BCVA) was measured on the Early Treatment Diabetic Retinopathy Study (ETDRS) chart at a starting distance of 4 meters. The BCVA letter score ranges from 0 to 100 (best score), and a gain in BCVA letter score from baseline indicates an improvement in visual acuity. The weighted estimates of the percentage of participants were based on the Cochran-Mantel Haenszel (CMH) weights stratified by baseline BCVA (≥69 vs. \<69 letters), prior IVT anti-VEGF therapy (yes vs. no), and region (U.S. and Canada vs. rest of the world; Asia and rest of the world were combined). Treatment policy strategy (i.e., all observed values used) and hypothetical strategy (i.e., all values censored after the occurrence of the intercurrent event) were applied to non-COVID-19 related and COVID-19 related intercurrent events, respectively. Missing data were not imputed. Invalid BCVA values were excluded. 95% confidence interval (CI) is a rounding of 95.04% CI.

Outcome measures

Outcome measures
Measure	A: Faricimab 6 mg Q8W n=315 Participants Participants randomized to Arm A received 6 milligrams (mg) faricimab intravitreal (IVT) injections once every 4 weeks (Q4W) to Week 20, followed by 6 mg faricimab IVT injections once every 8 weeks (Q8W) to Week 96, followed by the final study visit at Week 100.	B: Faricimab 6 mg PTI n=313 Participants Participants randomized to Arm B received 6 milligrams (mg) faricimab intravitreal (IVT) injections Q4W to at least Week 12, followed by a personalized treatment interval (PTI) dosing of 6 mg faricimab IVT injections up to once every 16 weeks (Q16W) through Week 96, followed by the final study visit at Week 100.	C: Aflibercept 2 mg Q8W n=312 Participants Participants randomized to Arm C received 2 milligrams (mg) aflibercept intravitreal (IVT) injections Q4W to Week 16, followed by 2 mg aflibercept IVT injections Q8W to Week 96, followed by the final study visit at Week 100.
Percentage of Participants With BCVA Snellen Equivalent of 20/40 or Better (BCVA ≥69 Letters) in the Study Eye Over Time, ITT Population Week 4	53.3 Percentage of participants Interval 48.4 to 58.1	60.0 Percentage of participants Interval 55.1 to 64.8	57.5 Percentage of participants Interval 52.6 to 62.4
Percentage of Participants With BCVA Snellen Equivalent of 20/40 or Better (BCVA ≥69 Letters) in the Study Eye Over Time, ITT Population Week 8	60.0 Percentage of participants Interval 55.1 to 64.9	65.5 Percentage of participants Interval 60.8 to 70.1	66.1 Percentage of participants Interval 61.4 to 70.8
Percentage of Participants With BCVA Snellen Equivalent of 20/40 or Better (BCVA ≥69 Letters) in the Study Eye Over Time, ITT Population Week 12	64.4 Percentage of participants Interval 59.4 to 69.3	69.3 Percentage of participants Interval 64.6 to 74.0	68.8 Percentage of participants Interval 64.1 to 73.6
Percentage of Participants With BCVA Snellen Equivalent of 20/40 or Better (BCVA ≥69 Letters) in the Study Eye Over Time, ITT Population Week 16	66.1 Percentage of participants Interval 61.1 to 71.2	70.6 Percentage of participants Interval 65.8 to 75.3	74.7 Percentage of participants Interval 70.1 to 79.2
Percentage of Participants With BCVA Snellen Equivalent of 20/40 or Better (BCVA ≥69 Letters) in the Study Eye Over Time, ITT Population Week 20	70.3 Percentage of participants Interval 65.4 to 75.3	69.7 Percentage of participants Interval 64.9 to 74.6	70.3 Percentage of participants Interval 65.5 to 75.1
Percentage of Participants With BCVA Snellen Equivalent of 20/40 or Better (BCVA ≥69 Letters) in the Study Eye Over Time, ITT Population Week 24	71.0 Percentage of participants Interval 66.1 to 76.0	76.0 Percentage of participants Interval 71.4 to 80.6	71.0 Percentage of participants Interval 66.3 to 75.8
Percentage of Participants With BCVA Snellen Equivalent of 20/40 or Better (BCVA ≥69 Letters) in the Study Eye Over Time, ITT Population Week 28	71.5 Percentage of participants Interval 66.5 to 76.4	74.5 Percentage of participants Interval 69.9 to 79.1	75.1 Percentage of participants Interval 70.4 to 79.8
Percentage of Participants With BCVA Snellen Equivalent of 20/40 or Better (BCVA ≥69 Letters) in the Study Eye Over Time, ITT Population Week 32	71.4 Percentage of participants Interval 66.3 to 76.5	74.1 Percentage of participants Interval 69.2 to 79.0	74.9 Percentage of participants Interval 70.1 to 79.7
Percentage of Participants With BCVA Snellen Equivalent of 20/40 or Better (BCVA ≥69 Letters) in the Study Eye Over Time, ITT Population Week 36	71.8 Percentage of participants Interval 66.8 to 76.9	79.4 Percentage of participants Interval 74.7 to 84.1	73.2 Percentage of participants Interval 68.1 to 78.2
Percentage of Participants With BCVA Snellen Equivalent of 20/40 or Better (BCVA ≥69 Letters) in the Study Eye Over Time, ITT Population Week 40	69.3 Percentage of participants Interval 64.2 to 74.4	75.1 Percentage of participants Interval 70.2 to 80.1	73.6 Percentage of participants Interval 68.5 to 78.7
Percentage of Participants With BCVA Snellen Equivalent of 20/40 or Better (BCVA ≥69 Letters) in the Study Eye Over Time, ITT Population Week 44	70.6 Percentage of participants Interval 65.4 to 75.7	77.7 Percentage of participants Interval 72.9 to 82.5	73.4 Percentage of participants Interval 68.3 to 78.4
Percentage of Participants With BCVA Snellen Equivalent of 20/40 or Better (BCVA ≥69 Letters) in the Study Eye Over Time, ITT Population Week 48	73.4 Percentage of participants Interval 68.4 to 78.4	78.3 Percentage of participants Interval 73.6 to 83.0	72.7 Percentage of participants Interval 67.6 to 77.8
Percentage of Participants With BCVA Snellen Equivalent of 20/40 or Better (BCVA ≥69 Letters) in the Study Eye Over Time, ITT Population Week 52	69.3 Percentage of participants Interval 63.9 to 74.6	76.6 Percentage of participants Interval 71.7 to 81.4	75.2 Percentage of participants Interval 70.2 to 80.2
Percentage of Participants With BCVA Snellen Equivalent of 20/40 or Better (BCVA ≥69 Letters) in the Study Eye Over Time, ITT Population Week 56	74.9 Percentage of participants Interval 69.9 to 79.9	79.5 Percentage of participants Interval 74.8 to 84.2	72.2 Percentage of participants Interval 67.0 to 77.4
Percentage of Participants With BCVA Snellen Equivalent of 20/40 or Better (BCVA ≥69 Letters) in the Study Eye Over Time, ITT Population Week 60	71.8 Percentage of participants Interval 66.6 to 76.9	76.6 Percentage of participants Interval 71.6 to 81.5	75.9 Percentage of participants Interval 70.9 to 80.9
Percentage of Participants With BCVA Snellen Equivalent of 20/40 or Better (BCVA ≥69 Letters) in the Study Eye Over Time, ITT Population Week 64	74.9 Percentage of participants Interval 69.8 to 79.9	76.2 Percentage of participants Interval 71.4 to 81.0	71.4 Percentage of participants Interval 66.3 to 76.5
Percentage of Participants With BCVA Snellen Equivalent of 20/40 or Better (BCVA ≥69 Letters) in the Study Eye Over Time, ITT Population Week 68	74.4 Percentage of participants Interval 69.2 to 79.7	78.0 Percentage of participants Interval 73.2 to 82.8	73.9 Percentage of participants Interval 68.9 to 78.9
Percentage of Participants With BCVA Snellen Equivalent of 20/40 or Better (BCVA ≥69 Letters) in the Study Eye Over Time, ITT Population Week 72	73.9 Percentage of participants Interval 68.6 to 79.1	76.8 Percentage of participants Interval 72.0 to 81.7	71.0 Percentage of participants Interval 65.8 to 76.1
Percentage of Participants With BCVA Snellen Equivalent of 20/40 or Better (BCVA ≥69 Letters) in the Study Eye Over Time, ITT Population Week 76	72.6 Percentage of participants Interval 67.2 to 78.0	77.0 Percentage of participants Interval 72.0 to 82.0	76.0 Percentage of participants Interval 71.1 to 81.0
Percentage of Participants With BCVA Snellen Equivalent of 20/40 or Better (BCVA ≥69 Letters) in the Study Eye Over Time, ITT Population Week 80	74.6 Percentage of participants Interval 69.3 to 79.9	77.5 Percentage of participants Interval 72.5 to 82.4	73.8 Percentage of participants Interval 68.7 to 78.9
Percentage of Participants With BCVA Snellen Equivalent of 20/40 or Better (BCVA ≥69 Letters) in the Study Eye Over Time, ITT Population Week 84	73.7 Percentage of participants Interval 68.4 to 79.1	77.2 Percentage of participants Interval 72.3 to 82.1	77.3 Percentage of participants Interval 72.5 to 82.2
Percentage of Participants With BCVA Snellen Equivalent of 20/40 or Better (BCVA ≥69 Letters) in the Study Eye Over Time, ITT Population Week 88	72.2 Percentage of participants Interval 66.7 to 77.7	76.2 Percentage of participants Interval 71.2 to 81.3	73.3 Percentage of participants Interval 68.0 to 78.5
Percentage of Participants With BCVA Snellen Equivalent of 20/40 or Better (BCVA ≥69 Letters) in the Study Eye Over Time, ITT Population Week 92	75.3 Percentage of participants Interval 70.0 to 80.6	78.4 Percentage of participants Interval 73.4 to 83.3	77.4 Percentage of participants Interval 72.6 to 82.2
Percentage of Participants With BCVA Snellen Equivalent of 20/40 or Better (BCVA ≥69 Letters) in the Study Eye Over Time, ITT Population Week 96	75.9 Percentage of participants Interval 70.6 to 81.2	74.3 Percentage of participants Interval 69.0 to 79.5	73.4 Percentage of participants Interval 68.3 to 78.5
Percentage of Participants With BCVA Snellen Equivalent of 20/40 or Better (BCVA ≥69 Letters) in the Study Eye Over Time, ITT Population Week 100	75.9 Percentage of participants Interval 70.7 to 81.1	70.3 Percentage of participants Interval 64.9 to 75.7	75.7 Percentage of participants Interval 70.8 to 80.7

SECONDARY outcome

Timeframe: Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, 56, 60, 64, 68, 72, 76, 80, 84, 88, 92, 96, and 100

Population: Treatment-Naive Population: all participants randomized in the study who had not received any intravitreal anti-VEGF agents in the study eye prior to randomization. Participants were grouped according to the treatment assigned at randomization. At each timepoint, only participants with non-missing, valid assessments were included in the analysis.

Best Corrected Visual Acuity (BCVA) was measured on the Early Treatment Diabetic Retinopathy Study (ETDRS) chart at a starting distance of 4 meters. The BCVA letter score ranges from 0 to 100 (best score), and a gain in BCVA letter score from baseline indicates an improvement in visual acuity. The weighted estimates of the percentage of participants were based on the Cochran-Mantel Haenszel (CMH) weights stratified by baseline BCVA (≥69 vs. \<69 letters) and region (U.S. and Canada vs. rest of the world; Asia and rest of the world were combined). Treatment policy strategy (i.e., all observed values used) and hypothetical strategy (i.e., all values censored after the occurrence of the intercurrent event) were applied to non-COVID-19 related and COVID-19 related intercurrent events, respectively. Missing data were not imputed. Invalid BCVA values were excluded from analysis. 95% confidence interval (CI) is a rounding of 95.04% CI.

Outcome measures

Outcome measures
Measure	A: Faricimab 6 mg Q8W n=238 Participants Participants randomized to Arm A received 6 milligrams (mg) faricimab intravitreal (IVT) injections once every 4 weeks (Q4W) to Week 20, followed by 6 mg faricimab IVT injections once every 8 weeks (Q8W) to Week 96, followed by the final study visit at Week 100.	B: Faricimab 6 mg PTI n=245 Participants Participants randomized to Arm B received 6 milligrams (mg) faricimab intravitreal (IVT) injections Q4W to at least Week 12, followed by a personalized treatment interval (PTI) dosing of 6 mg faricimab IVT injections up to once every 16 weeks (Q16W) through Week 96, followed by the final study visit at Week 100.	C: Aflibercept 2 mg Q8W n=242 Participants Participants randomized to Arm C received 2 milligrams (mg) aflibercept intravitreal (IVT) injections Q4W to Week 16, followed by 2 mg aflibercept IVT injections Q8W to Week 96, followed by the final study visit at Week 100.
Percentage of Participants With BCVA Snellen Equivalent of 20/40 or Better (BCVA ≥69 Letters) in the Study Eye Over Time, Treatment-Naive Population Week 4	55.7 Percentage of participants Interval 50.1 to 61.2	60.4 Percentage of participants Interval 55.0 to 65.8	60.4 Percentage of participants Interval 54.9 to 65.9
Percentage of Participants With BCVA Snellen Equivalent of 20/40 or Better (BCVA ≥69 Letters) in the Study Eye Over Time, Treatment-Naive Population Week 8	62.0 Percentage of participants Interval 56.5 to 67.6	66.5 Percentage of participants Interval 61.3 to 71.6	69.6 Percentage of participants Interval 64.3 to 74.8
Percentage of Participants With BCVA Snellen Equivalent of 20/40 or Better (BCVA ≥69 Letters) in the Study Eye Over Time, Treatment-Naive Population Week 12	66.2 Percentage of participants Interval 60.5 to 71.8	69.3 Percentage of participants Interval 64.1 to 74.5	70.6 Percentage of participants Interval 65.3 to 75.9
Percentage of Participants With BCVA Snellen Equivalent of 20/40 or Better (BCVA ≥69 Letters) in the Study Eye Over Time, Treatment-Naive Population Week 16	68.5 Percentage of participants Interval 62.8 to 74.2	68.5 Percentage of participants Interval 63.1 to 74.0	75.8 Percentage of participants Interval 70.8 to 80.9
Percentage of Participants With BCVA Snellen Equivalent of 20/40 or Better (BCVA ≥69 Letters) in the Study Eye Over Time, Treatment-Naive Population Week 20	72.7 Percentage of participants Interval 67.1 to 78.2	67.8 Percentage of participants Interval 62.2 to 73.4	72.0 Percentage of participants Interval 66.7 to 77.3
Percentage of Participants With BCVA Snellen Equivalent of 20/40 or Better (BCVA ≥69 Letters) in the Study Eye Over Time, Treatment-Naive Population Week 24	73.7 Percentage of participants Interval 68.2 to 79.3	74.5 Percentage of participants Interval 69.2 to 79.8	72.6 Percentage of participants Interval 67.3 to 77.9
Percentage of Participants With BCVA Snellen Equivalent of 20/40 or Better (BCVA ≥69 Letters) in the Study Eye Over Time, Treatment-Naive Population Week 28	73.7 Percentage of participants Interval 68.2 to 79.3	73.1 Percentage of participants Interval 67.8 to 78.4	77.0 Percentage of participants Interval 71.8 to 82.2
Percentage of Participants With BCVA Snellen Equivalent of 20/40 or Better (BCVA ≥69 Letters) in the Study Eye Over Time, Treatment-Naive Population Week 32	71.8 Percentage of participants Interval 65.8 to 77.7	72.4 Percentage of participants Interval 66.7 to 78.1	75.8 Percentage of participants Interval 70.4 to 81.2
Percentage of Participants With BCVA Snellen Equivalent of 20/40 or Better (BCVA ≥69 Letters) in the Study Eye Over Time, Treatment-Naive Population Week 36	74.7 Percentage of participants Interval 68.9 to 80.5	79.4 Percentage of participants Interval 74.0 to 84.7	73.4 Percentage of participants Interval 67.6 to 79.1
Percentage of Participants With BCVA Snellen Equivalent of 20/40 or Better (BCVA ≥69 Letters) in the Study Eye Over Time, Treatment-Naive Population Week 40	70.6 Percentage of participants Interval 64.7 to 76.6	74.6 Percentage of participants Interval 68.9 to 80.3	75.8 Percentage of participants Interval 70.2 to 81.4
Percentage of Participants With BCVA Snellen Equivalent of 20/40 or Better (BCVA ≥69 Letters) in the Study Eye Over Time, Treatment-Naive Population Week 44	71.1 Percentage of participants Interval 65.2 to 77.1	76.9 Percentage of participants Interval 71.3 to 82.4	76.4 Percentage of participants Interval 70.8 to 82.0
Percentage of Participants With BCVA Snellen Equivalent of 20/40 or Better (BCVA ≥69 Letters) in the Study Eye Over Time, Treatment-Naive Population Week 48	74.3 Percentage of participants Interval 68.6 to 80.0	75.7 Percentage of participants Interval 70.2 to 81.2	75.3 Percentage of participants Interval 69.8 to 80.9
Percentage of Participants With BCVA Snellen Equivalent of 20/40 or Better (BCVA ≥69 Letters) in the Study Eye Over Time, Treatment-Naive Population Week 52	71.7 Percentage of participants Interval 65.6 to 77.7	74.4 Percentage of participants Interval 68.7 to 80.1	77.5 Percentage of participants Interval 71.9 to 83.0
Percentage of Participants With BCVA Snellen Equivalent of 20/40 or Better (BCVA ≥69 Letters) in the Study Eye Over Time, Treatment-Naive Population Week 56	76.9 Percentage of participants Interval 71.3 to 82.5	77.9 Percentage of participants Interval 72.4 to 83.4	74.0 Percentage of participants Interval 68.2 to 79.7
Percentage of Participants With BCVA Snellen Equivalent of 20/40 or Better (BCVA ≥69 Letters) in the Study Eye Over Time, Treatment-Naive Population Week 60	73.4 Percentage of participants Interval 67.5 to 79.3	75.2 Percentage of participants Interval 69.4 to 81.0	78.3 Percentage of participants Interval 72.8 to 83.8
Percentage of Participants With BCVA Snellen Equivalent of 20/40 or Better (BCVA ≥69 Letters) in the Study Eye Over Time, Treatment-Naive Population Week 64	77.0 Percentage of participants Interval 71.2 to 82.7	75.5 Percentage of participants Interval 69.9 to 81.0	74.4 Percentage of participants Interval 68.9 to 80.0
Percentage of Participants With BCVA Snellen Equivalent of 20/40 or Better (BCVA ≥69 Letters) in the Study Eye Over Time, Treatment-Naive Population Week 68	77.6 Percentage of participants Interval 71.7 to 83.5	77.9 Percentage of participants Interval 72.4 to 83.3	75.5 Percentage of participants Interval 69.9 to 81.0
Percentage of Participants With BCVA Snellen Equivalent of 20/40 or Better (BCVA ≥69 Letters) in the Study Eye Over Time, Treatment-Naive Population Week 72	76.7 Percentage of participants Interval 70.7 to 82.6	75.9 Percentage of participants Interval 70.3 to 81.4	74.5 Percentage of participants Interval 68.9 to 80.1
Percentage of Participants With BCVA Snellen Equivalent of 20/40 or Better (BCVA ≥69 Letters) in the Study Eye Over Time, Treatment-Naive Population Week 76	72.7 Percentage of participants Interval 66.3 to 79.1	75.8 Percentage of participants Interval 70.1 to 81.5	78.0 Percentage of participants Interval 72.6 to 83.3
Percentage of Participants With BCVA Snellen Equivalent of 20/40 or Better (BCVA ≥69 Letters) in the Study Eye Over Time, Treatment-Naive Population Week 80	76.4 Percentage of participants Interval 70.2 to 82.6	76.8 Percentage of participants Interval 71.2 to 82.5	76.5 Percentage of participants Interval 70.9 to 82.1
Percentage of Participants With BCVA Snellen Equivalent of 20/40 or Better (BCVA ≥69 Letters) in the Study Eye Over Time, Treatment-Naive Population Week 84	75.7 Percentage of participants Interval 69.5 to 81.9	77.8 Percentage of participants Interval 72.3 to 83.3	77.8 Percentage of participants Interval 72.4 to 83.2
Percentage of Participants With BCVA Snellen Equivalent of 20/40 or Better (BCVA ≥69 Letters) in the Study Eye Over Time, Treatment-Naive Population Week 88	71.8 Percentage of participants Interval 65.2 to 78.3	75.7 Percentage of participants Interval 69.9 to 81.5	76.0 Percentage of participants Interval 70.1 to 81.9
Percentage of Participants With BCVA Snellen Equivalent of 20/40 or Better (BCVA ≥69 Letters) in the Study Eye Over Time, Treatment-Naive Population Week 92	75.9 Percentage of participants Interval 69.7 to 82.1	77.7 Percentage of participants Interval 71.9 to 83.4	79.9 Percentage of participants Interval 74.7 to 85.2
Percentage of Participants With BCVA Snellen Equivalent of 20/40 or Better (BCVA ≥69 Letters) in the Study Eye Over Time, Treatment-Naive Population Week 96	77.3 Percentage of participants Interval 71.1 to 83.4	73.5 Percentage of participants Interval 67.4 to 79.5	75.5 Percentage of participants Interval 69.9 to 81.2
Percentage of Participants With BCVA Snellen Equivalent of 20/40 or Better (BCVA ≥69 Letters) in the Study Eye Over Time, Treatment-Naive Population Week 100	77.6 Percentage of participants Interval 71.6 to 83.6	70.8 Percentage of participants Interval 64.6 to 76.9	77.0 Percentage of participants Interval 71.4 to 82.5

SECONDARY outcome

Timeframe: Baseline, average of Weeks 48, 52, and 56

Population: ITT Population and Treatment-Naive Population. Only participants with at least one non-missing, valid assessment at Weeks 48, 52, or 56 were included in the analysis.

Outcome measures

Outcome measures
Measure	A: Faricimab 6 mg Q8W n=271 Participants Participants randomized to Arm A received 6 milligrams (mg) faricimab intravitreal (IVT) injections once every 4 weeks (Q4W) to Week 20, followed by 6 mg faricimab IVT injections once every 8 weeks (Q8W) to Week 96, followed by the final study visit at Week 100.	B: Faricimab 6 mg PTI n=276 Participants Participants randomized to Arm B received 6 milligrams (mg) faricimab intravitreal (IVT) injections Q4W to at least Week 12, followed by a personalized treatment interval (PTI) dosing of 6 mg faricimab IVT injections up to once every 16 weeks (Q16W) through Week 96, followed by the final study visit at Week 100.	C: Aflibercept 2 mg Q8W n=276 Participants Participants randomized to Arm C received 2 milligrams (mg) aflibercept intravitreal (IVT) injections Q4W to Week 16, followed by 2 mg aflibercept IVT injections Q8W to Week 96, followed by the final study visit at Week 100.
Percentage of Participants With BCVA Snellen Equivalent of 20/200 or Worse (BCVA ≤38 Letters) in the Study Eye Averaged Over Weeks 48, 52, and 56, ITT and Treatment-Naive Populations ITT Population	2.3 Percentage of participants Interval 0.5 to 4.1	1.9 Percentage of participants Interval 0.3 to 3.5	1.7 Percentage of participants Interval 0.3 to 3.2
Percentage of Participants With BCVA Snellen Equivalent of 20/200 or Worse (BCVA ≤38 Letters) in the Study Eye Averaged Over Weeks 48, 52, and 56, ITT and Treatment-Naive Populations Treatment-Naive Population	2.6 Percentage of participants Interval 0.4 to 4.8	1.9 Percentage of participants Interval 0.1 to 3.7	1.8 Percentage of participants Interval 0.1 to 3.5

SECONDARY outcome

Timeframe: Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, 56, 60, 64, 68, 72, 76, 80, 84, 88, 92, 96, and 100

Best Corrected Visual Acuity (BCVA) was measured on the Early Treatment Diabetic Retinopathy Study (ETDRS) chart at a starting distance of 4 meters. The BCVA letter score ranges from 0 to 100 (best score), and a gain in BCVA letter score from baseline indicates an improvement invisual acuity. The weighted estimates of the percentage of participants were based on the Cochran-Mantel Haenszel (CMH) weights stratified by baseline BCVA (≥64 vs. \<64 letters), prior IVT anti-VEGF therapy (yes vs. no), and region (U.S. and Canada vs. rest of the world; Asia and rest of the world were combined). Treatment policy strategy (i.e., all observed values used) and hypothetical strategy (i.e., all values censored after the occurrence of the intercurrent event) were applied to non-COVID-19 related and COVID-19 related intercurrent events, respectively. Missing data were not imputed. Invalid BCVA values were excluded from analysis. 95% confidence interval (CI) is a rounding of 95.04% CI.

Outcome measures

Outcome measures
Measure	A: Faricimab 6 mg Q8W n=315 Participants Participants randomized to Arm A received 6 milligrams (mg) faricimab intravitreal (IVT) injections once every 4 weeks (Q4W) to Week 20, followed by 6 mg faricimab IVT injections once every 8 weeks (Q8W) to Week 96, followed by the final study visit at Week 100.	B: Faricimab 6 mg PTI n=313 Participants Participants randomized to Arm B received 6 milligrams (mg) faricimab intravitreal (IVT) injections Q4W to at least Week 12, followed by a personalized treatment interval (PTI) dosing of 6 mg faricimab IVT injections up to once every 16 weeks (Q16W) through Week 96, followed by the final study visit at Week 100.	C: Aflibercept 2 mg Q8W n=312 Participants Participants randomized to Arm C received 2 milligrams (mg) aflibercept intravitreal (IVT) injections Q4W to Week 16, followed by 2 mg aflibercept IVT injections Q8W to Week 96, followed by the final study visit at Week 100.
Percentage of Participants With BCVA Snellen Equivalent of 20/200 or Worse (BCVA ≤38 Letters) in the Study Eye Over Time, ITT Population Week 4	1.9 Percentage of participants Interval 0.4 to 3.4	2.6 Percentage of participants Interval 0.9 to 4.3	1.6 Percentage of participants Interval 0.2 to 3.0
Percentage of Participants With BCVA Snellen Equivalent of 20/200 or Worse (BCVA ≤38 Letters) in the Study Eye Over Time, ITT Population Week 8	2.0 Percentage of participants Interval 0.4 to 3.5	3.0 Percentage of participants Interval 1.1 to 4.8	2.0 Percentage of participants Interval 0.4 to 3.5
Percentage of Participants With BCVA Snellen Equivalent of 20/200 or Worse (BCVA ≤38 Letters) in the Study Eye Over Time, ITT Population Week 12	1.6 Percentage of participants Interval 0.2 to 3.0	2.0 Percentage of participants Interval 0.5 to 3.5	1.6 Percentage of participants Interval 0.2 to 3.0
Percentage of Participants With BCVA Snellen Equivalent of 20/200 or Worse (BCVA ≤38 Letters) in the Study Eye Over Time, ITT Population Week 16	0.7 Percentage of participants Interval 0.0 to 1.6	2.1 Percentage of participants Interval 0.5 to 3.7	1.6 Percentage of participants Interval 0.2 to 3.0
Percentage of Participants With BCVA Snellen Equivalent of 20/200 or Worse (BCVA ≤38 Letters) in the Study Eye Over Time, ITT Population Week 20	1.3 Percentage of participants Interval 0.0 to 2.7	1.7 Percentage of participants Interval 0.3 to 3.2	1.7 Percentage of participants Interval 0.2 to 3.1
Percentage of Participants With BCVA Snellen Equivalent of 20/200 or Worse (BCVA ≤38 Letters) in the Study Eye Over Time, ITT Population Week 24	0.7 Percentage of participants Interval 0.0 to 1.6	1.7 Percentage of participants Interval 0.3 to 3.2	1.7 Percentage of participants Interval 0.3 to 3.1
Percentage of Participants With BCVA Snellen Equivalent of 20/200 or Worse (BCVA ≤38 Letters) in the Study Eye Over Time, ITT Population Week 28	1.4 Percentage of participants Interval 0.1 to 2.8	1.4 Percentage of participants Interval 0.1 to 2.8	1.4 Percentage of participants Interval 0.1 to 2.7
Percentage of Participants With BCVA Snellen Equivalent of 20/200 or Worse (BCVA ≤38 Letters) in the Study Eye Over Time, ITT Population Week 32	1.1 Percentage of participants Interval 0.0 to 2.4	1.2 Percentage of participants Interval 0.0 to 2.4	1.8 Percentage of participants Interval 0.2 to 3.3
Percentage of Participants With BCVA Snellen Equivalent of 20/200 or Worse (BCVA ≤38 Letters) in the Study Eye Over Time, ITT Population Week 36	1.6 Percentage of participants Interval 0.1 to 3.1	1.6 Percentage of participants Interval 0.1 to 3.1	1.5 Percentage of participants Interval 0.1 to 3.0
Percentage of Participants With BCVA Snellen Equivalent of 20/200 or Worse (BCVA ≤38 Letters) in the Study Eye Over Time, ITT Population Week 40	1.5 Percentage of participants Interval 0.1 to 3.0	2.3 Percentage of participants Interval 0.5 to 4.1	1.5 Percentage of participants Interval 0.1 to 2.9
Percentage of Participants With BCVA Snellen Equivalent of 20/200 or Worse (BCVA ≤38 Letters) in the Study Eye Over Time, ITT Population Week 44	3.1 Percentage of participants Interval 1.0 to 5.2	1.9 Percentage of participants Interval 0.3 to 3.6	1.4 Percentage of participants Interval 0.1 to 2.8
Percentage of Participants With BCVA Snellen Equivalent of 20/200 or Worse (BCVA ≤38 Letters) in the Study Eye Over Time, ITT Population Week 48	1.6 Percentage of participants Interval 0.1 to 3.1	2.3 Percentage of participants Interval 0.5 to 4.1	1.8 Percentage of participants Interval 0.3 to 3.3
Percentage of Participants With BCVA Snellen Equivalent of 20/200 or Worse (BCVA ≤38 Letters) in the Study Eye Over Time, ITT Population Week 52	2.0 Percentage of participants Interval 0.3 to 3.8	1.5 Percentage of participants Interval 0.1 to 3.0	1.5 Percentage of participants Interval 0.1 to 2.9
Percentage of Participants With BCVA Snellen Equivalent of 20/200 or Worse (BCVA ≤38 Letters) in the Study Eye Over Time, ITT Population Week 56	1.5 Percentage of participants Interval 0.0 to 3.0	1.6 Percentage of participants Interval 0.1 to 3.1	1.9 Percentage of participants Interval 0.3 to 3.5
Percentage of Participants With BCVA Snellen Equivalent of 20/200 or Worse (BCVA ≤38 Letters) in the Study Eye Over Time, ITT Population Week 60	1.9 Percentage of participants Interval 0.3 to 3.5	1.2 Percentage of participants Interval 0.0 to 2.5	1.4 Percentage of participants Interval 0.1 to 2.8
Percentage of Participants With BCVA Snellen Equivalent of 20/200 or Worse (BCVA ≤38 Letters) in the Study Eye Over Time, ITT Population Week 64	1.2 Percentage of participants Interval 0.0 to 2.6	2.5 Percentage of participants Interval 0.6 to 4.3	1.8 Percentage of participants Interval 0.2 to 3.3
Percentage of Participants With BCVA Snellen Equivalent of 20/200 or Worse (BCVA ≤38 Letters) in the Study Eye Over Time, ITT Population Week 68	1.3 Percentage of participants Interval 0.0 to 2.7	2.4 Percentage of participants Interval 0.6 to 4.3	1.8 Percentage of participants Interval 0.3 to 3.4
Percentage of Participants With BCVA Snellen Equivalent of 20/200 or Worse (BCVA ≤38 Letters) in the Study Eye Over Time, ITT Population Week 72	1.3 Percentage of participants Interval 0.0 to 2.7	1.6 Percentage of participants Interval 0.1 to 3.1	1.5 Percentage of participants Interval 0.1 to 2.9
Percentage of Participants With BCVA Snellen Equivalent of 20/200 or Worse (BCVA ≤38 Letters) in the Study Eye Over Time, ITT Population Week 76	0.9 Percentage of participants Interval 0.0 to 2.1	1.6 Percentage of participants Interval 0.1 to 3.2	3.4 Percentage of participants Interval 1.3 to 5.6
Percentage of Participants With BCVA Snellen Equivalent of 20/200 or Worse (BCVA ≤38 Letters) in the Study Eye Over Time, ITT Population Week 80	0.9 Percentage of participants Interval 0.0 to 2.1	2.0 Percentage of participants Interval 0.3 to 3.8	3.0 Percentage of participants Interval 1.0 to 5.0
Percentage of Participants With BCVA Snellen Equivalent of 20/200 or Worse (BCVA ≤38 Letters) in the Study Eye Over Time, ITT Population Week 84	0.9 Percentage of participants Interval 0.0 to 2.1	1.6 Percentage of participants Interval 0.1 to 3.2	1.0 Percentage of participants Interval 0.0 to 2.2
Percentage of Participants With BCVA Snellen Equivalent of 20/200 or Worse (BCVA ≤38 Letters) in the Study Eye Over Time, ITT Population Week 88	1.3 Percentage of participants Interval 0.0 to 2.7	1.7 Percentage of participants Interval 0.1 to 3.2	2.0 Percentage of participants Interval 0.3 to 3.8
Percentage of Participants With BCVA Snellen Equivalent of 20/200 or Worse (BCVA ≤38 Letters) in the Study Eye Over Time, ITT Population Week 92	2.2 Percentage of participants Interval 0.3 to 4.0	2.1 Percentage of participants Interval 0.4 to 3.9	2.8 Percentage of participants Interval 0.8 to 4.8
Percentage of Participants With BCVA Snellen Equivalent of 20/200 or Worse (BCVA ≤38 Letters) in the Study Eye Over Time, ITT Population Week 96	1.7 Percentage of participants Interval 0.1 to 3.4	2.1 Percentage of participants Interval 0.3 to 3.8	0.9 Percentage of participants Interval 0.0 to 2.1
Percentage of Participants With BCVA Snellen Equivalent of 20/200 or Worse (BCVA ≤38 Letters) in the Study Eye Over Time, ITT Population Week 100	2.5 Percentage of participants Interval 0.5 to 4.5	2.1 Percentage of participants Interval 0.3 to 3.8	1.2 Percentage of participants Interval 0.0 to 2.6

SECONDARY outcome

Timeframe: Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, 56, 60, 64, 68, 72, 76, 80, 84, 88, 92, 96, and 100

Population: Treatment-Naive Population: all participants randomized in the study who had not received any intravitreal anti-VEGF agents in the study eye prior to randomization. Participants were grouped according to the treatment assigned at randomization. At each timepoint, only participants with non-missing, valid assessments were included in the analysis.

Best Corrected Visual Acuity (BCVA) was measured on the Early Treatment Diabetic Retinopathy Study (ETDRS) chart at a starting distance of 4 meters. The BCVA letter score ranges from 0 to 100 (best score attainable), and a gain in BCVA letter score from baseline indicates an improvement in visual acuity. The weighted estimates of the percentage of participants were based on the Cochran-Mantel Haenszel (CMH) weights stratified by baseline BCVA (≥64 vs. \<64 letters) and region (U.S. and Canada vs. rest of the world; Asia and rest of the world were combined). Treatment policy strategy (i.e., all observed values used) and hypothetical strategy (i.e., all values censored after the occurrence of the intercurrent event) were applied to non-COVID-19 related and COVID-19 related intercurrent events, respectively. Missing data were not imputed. Invalid BCVA values were excluded from analysis. 95% confidence interval (CI) is a rounding of 95.04% CI.

Outcome measures

SECONDARY outcome

Timeframe: Baseline, Weeks 16, 52, and 96

Population: ITT Population: all participants who were randomized in the study, grouped according to the treatment assigned at randomization. Only participants with non-missing, valid assessments at Baseline and each timepoint were included in the analysis.

The Early Treatment Diabetic Retinopathy Study (ETDRS) Diabetic Retinopathy Severity Scale (DRSS) classifies diabetic retinopathy into 12 severity steps ranging from absence of retinopathy to advanced proliferative diabetic retinopathy. Ocular imaging assessments were made independently by a central reading center. The weighted estimates of the percentage of participants were based on the Cochran-Mantel Haenszel (CMH) weights stratified by baseline BCVA (≥64 vs. \<64 letters), prior IVT anti-VEGF therapy (yes vs. no), and region (U.S. and Canada vs. rest of the world; Asia and rest of the world regions were combined). Treatment policy strategy (i.e., all observed values used) and hypothetical strategy (i.e., all values censored after the occurrence of the intercurrent event) were applied to non-COVID-19 related and COVID-19 related intercurrent events, respectively. Missing data were not imputed. 95% confidence interval (CI) is a rounding of 95.04% CI.

Outcome measures

Outcome measures
Measure	A: Faricimab 6 mg Q8W n=315 Participants Participants randomized to Arm A received 6 milligrams (mg) faricimab intravitreal (IVT) injections once every 4 weeks (Q4W) to Week 20, followed by 6 mg faricimab IVT injections once every 8 weeks (Q8W) to Week 96, followed by the final study visit at Week 100.	B: Faricimab 6 mg PTI n=313 Participants Participants randomized to Arm B received 6 milligrams (mg) faricimab intravitreal (IVT) injections Q4W to at least Week 12, followed by a personalized treatment interval (PTI) dosing of 6 mg faricimab IVT injections up to once every 16 weeks (Q16W) through Week 96, followed by the final study visit at Week 100.	C: Aflibercept 2 mg Q8W n=312 Participants Participants randomized to Arm C received 2 milligrams (mg) aflibercept intravitreal (IVT) injections Q4W to Week 16, followed by 2 mg aflibercept IVT injections Q8W to Week 96, followed by the final study visit at Week 100.
Percentage of Participants With a ≥2-Step Diabetic Retinopathy Severity Improvement From Baseline on the ETDRS Diabetic Retinopathy Severity Scale in the Study Eye Over Time, ITT Population Week 16	36.7 Percentage of participants Interval 31.2 to 42.3	35.0 Percentage of participants Interval 29.6 to 40.5	28.9 Percentage of participants Interval 23.9 to 34.0
Percentage of Participants With a ≥2-Step Diabetic Retinopathy Severity Improvement From Baseline on the ETDRS Diabetic Retinopathy Severity Scale in the Study Eye Over Time, ITT Population Week 52	46.2 Percentage of participants Interval 40.0 to 52.3	42.3 Percentage of participants Interval 36.4 to 48.3	35.4 Percentage of participants Interval 29.6 to 41.2
Percentage of Participants With a ≥2-Step Diabetic Retinopathy Severity Improvement From Baseline on the ETDRS Diabetic Retinopathy Severity Scale in the Study Eye Over Time, ITT Population Week 96	51.4 Percentage of participants Interval 44.8 to 57.9	42.8 Percentage of participants Interval 36.6 to 49.0	42.2 Percentage of participants Interval 35.9 to 48.5

SECONDARY outcome

Timeframe: Baseline, Weeks 16, 52, and 96

Population: Treatment-Naive Population: all participants randomized in the study who had not received any intravitreal anti-VEGF agents in the study eye prior to randomization. Participants were grouped according to the treatment assigned at randomization. Only participants with non-missing, valid assessments at Baseline and each timepoint were included in the analysis.

The Early Treatment Diabetic Retinopathy Study (ETDRS) Diabetic Retinopathy Severity Scale (DRSS) classifies diabetic retinopathy into 12 severity steps ranging from absence of retinopathy to advanced proliferative diabetic retinopathy. Ocular imaging assessments were made independently by a central reading center. The weighted estimates of the percentage of participants were based on the Cochran-Mantel Haenszel (CMH) weights stratified by baseline BCVA (≥64 vs. \<64 letters) and region (U.S. and Canada vs. rest of the world; Asia and rest of the world regions were combined). Treatment policy strategy (i.e., all observed values used) and hypothetical strategy (i.e., all values censored after the occurrence of the intercurrent event) were applied to non-COVID-19 related and COVID-19 related intercurrent events, respectively. Missing data were not imputed. 95% confidence interval (CI) is a rounding of 95.04% CI.

Outcome measures

Outcome measures
Measure	A: Faricimab 6 mg Q8W n=238 Participants Participants randomized to Arm A received 6 milligrams (mg) faricimab intravitreal (IVT) injections once every 4 weeks (Q4W) to Week 20, followed by 6 mg faricimab IVT injections once every 8 weeks (Q8W) to Week 96, followed by the final study visit at Week 100.	B: Faricimab 6 mg PTI n=245 Participants Participants randomized to Arm B received 6 milligrams (mg) faricimab intravitreal (IVT) injections Q4W to at least Week 12, followed by a personalized treatment interval (PTI) dosing of 6 mg faricimab IVT injections up to once every 16 weeks (Q16W) through Week 96, followed by the final study visit at Week 100.	C: Aflibercept 2 mg Q8W n=242 Participants Participants randomized to Arm C received 2 milligrams (mg) aflibercept intravitreal (IVT) injections Q4W to Week 16, followed by 2 mg aflibercept IVT injections Q8W to Week 96, followed by the final study visit at Week 100.
Percentage of Participants With a ≥2-Step Diabetic Retinopathy Severity Improvement From Baseline on the ETDRS Diabetic Retinopathy Severity Scale in the Study Eye Over Time, Treatment-Naive Population Week 16	39.3 Percentage of participants Interval 32.7 to 45.8	39.5 Percentage of participants Interval 33.2 to 45.9	33.3 Percentage of participants Interval 27.1 to 39.4
Percentage of Participants With a ≥2-Step Diabetic Retinopathy Severity Improvement From Baseline on the ETDRS Diabetic Retinopathy Severity Scale in the Study Eye Over Time, Treatment-Naive Population Week 52	49.5 Percentage of participants Interval 42.3 to 56.8	47.4 Percentage of participants Interval 40.5 to 54.4	42.3 Percentage of participants Interval 35.3 to 49.3
Percentage of Participants With a ≥2-Step Diabetic Retinopathy Severity Improvement From Baseline on the ETDRS Diabetic Retinopathy Severity Scale in the Study Eye Over Time, Treatment-Naive Population Week 96	52.3 Percentage of participants Interval 44.6 to 60.1	47.0 Percentage of participants Interval 39.7 to 54.2	49.1 Percentage of participants Interval 41.7 to 56.6

SECONDARY outcome

Timeframe: Baseline, Weeks 16, 52, and 96

The Early Treatment Diabetic Retinopathy Study (ETDRS) Diabetic Retinopathy Severity Scale (DRSS) classifies diabetic retinopathy into 12 severity steps ranging from absence of retinopathy to advanced proliferative diabetic retinopathy. Ocular imaging assessments were made independently by a central reading center. The weighted estimates of the percentage of participants were based on the Cochran-Mantel Haenszel (CMH) weights stratified by baseline BCVA (≥64 vs. \<64 letters), prior IVT anti-VEGF therapy (yes vs. no), and region (U.S. and Canada vs. rest of the world; Asia and rest of the world regions were combined). Treatment policy strategy (i.e., all observed values used) and hypothetical strategy (i.e., all values censored after the occurrence of the intercurrent event) were applied to non-COVID-19 related and COVID-19 related intercurrent events, respectively. Missing data were not imputed. 95% confidence interval (CI) is a rounding of 95.04% CI.

Outcome measures

Outcome measures
Measure	A: Faricimab 6 mg Q8W n=315 Participants Participants randomized to Arm A received 6 milligrams (mg) faricimab intravitreal (IVT) injections once every 4 weeks (Q4W) to Week 20, followed by 6 mg faricimab IVT injections once every 8 weeks (Q8W) to Week 96, followed by the final study visit at Week 100.	B: Faricimab 6 mg PTI n=313 Participants Participants randomized to Arm B received 6 milligrams (mg) faricimab intravitreal (IVT) injections Q4W to at least Week 12, followed by a personalized treatment interval (PTI) dosing of 6 mg faricimab IVT injections up to once every 16 weeks (Q16W) through Week 96, followed by the final study visit at Week 100.	C: Aflibercept 2 mg Q8W n=312 Participants Participants randomized to Arm C received 2 milligrams (mg) aflibercept intravitreal (IVT) injections Q4W to Week 16, followed by 2 mg aflibercept IVT injections Q8W to Week 96, followed by the final study visit at Week 100.
Percentage of Participants With a ≥3-Step Diabetic Retinopathy Severity Improvement From Baseline on the ETDRS Diabetic Retinopathy Severity Scale in the Study Eye Over Time, ITT Population Week 16	12.7 Percentage of participants Interval 8.8 to 16.5	12.8 Percentage of participants Interval 9.0 to 16.6	10.3 Percentage of participants Interval 6.8 to 13.8
Percentage of Participants With a ≥3-Step Diabetic Retinopathy Severity Improvement From Baseline on the ETDRS Diabetic Retinopathy Severity Scale in the Study Eye Over Time, ITT Population Week 52	17.0 Percentage of participants Interval 12.3 to 21.6	15.3 Percentage of participants Interval 10.9 to 19.8	14.2 Percentage of participants Interval 10.0 to 18.5
Percentage of Participants With a ≥3-Step Diabetic Retinopathy Severity Improvement From Baseline on the ETDRS Diabetic Retinopathy Severity Scale in the Study Eye Over Time, ITT Population Week 96	22.4 Percentage of participants Interval 16.9 to 27.8	14.6 Percentage of participants Interval 10.0 to 19.1	20.9 Percentage of participants Interval 15.8 to 26.0

SECONDARY outcome

Timeframe: Baseline, Weeks 16, 52, and 96

Population: Treatment-Naive Population: all participants randomized in the study who had not received any intravitreal anti-VEGF agents in the study eye prior to randomization. Participants were grouped according to the treatment assigned at randomization. Only participants with non-missing, valid assessments at Baseline and each timepoint were included in the analysis.

The Early Treatment Diabetic Retinopathy Study (ETDRS) Diabetic Retinopathy Severity Scale (DRSS) classifies diabetic retinopathy into 12 severity steps ranging from absence of retinopathy to advanced proliferative diabetic retinopathy. Ocular imaging assessments were made independently by a central reading center. The weighted estimates of the percentage of participants were based on the Cochran-Mantel Haenszel (CMH) weights stratified by baseline BCVA (≥64 vs. \<64 letters) and region (U.S. and Canada vs. rest of the world; Asia and rest of the world regions were combined). Treatment policy strategy (i.e., all observed values used) and hypothetical strategy (i.e., all values censored after the occurrence of the intercurrent event) were applied to non-COVID-19 related and COVID-19 related intercurrent events, respectively. Missing data were not imputed. 95% confidence interval (CI) is a rounding of 95.04% CI.

Outcome measures

Outcome measures
Measure	A: Faricimab 6 mg Q8W n=238 Participants Participants randomized to Arm A received 6 milligrams (mg) faricimab intravitreal (IVT) injections once every 4 weeks (Q4W) to Week 20, followed by 6 mg faricimab IVT injections once every 8 weeks (Q8W) to Week 96, followed by the final study visit at Week 100.	B: Faricimab 6 mg PTI n=245 Participants Participants randomized to Arm B received 6 milligrams (mg) faricimab intravitreal (IVT) injections Q4W to at least Week 12, followed by a personalized treatment interval (PTI) dosing of 6 mg faricimab IVT injections up to once every 16 weeks (Q16W) through Week 96, followed by the final study visit at Week 100.	C: Aflibercept 2 mg Q8W n=242 Participants Participants randomized to Arm C received 2 milligrams (mg) aflibercept intravitreal (IVT) injections Q4W to Week 16, followed by 2 mg aflibercept IVT injections Q8W to Week 96, followed by the final study visit at Week 100.
Percentage of Participants With a ≥3-Step Diabetic Retinopathy Severity Improvement From Baseline on the ETDRS Diabetic Retinopathy Severity Scale in the Study Eye Over Time, Treatment-Naive Population Week 16	14.4 Percentage of participants Interval 9.7 to 19.1	15.1 Percentage of participants Interval 10.4 to 19.8	10.4 Percentage of participants Interval 6.4 to 14.4
Percentage of Participants With a ≥3-Step Diabetic Retinopathy Severity Improvement From Baseline on the ETDRS Diabetic Retinopathy Severity Scale in the Study Eye Over Time, Treatment-Naive Population Week 52	19.5 Percentage of participants Interval 13.7 to 25.2	17.4 Percentage of participants Interval 12.1 to 22.8	16.4 Percentage of participants Interval 11.2 to 21.6
Percentage of Participants With a ≥3-Step Diabetic Retinopathy Severity Improvement From Baseline on the ETDRS Diabetic Retinopathy Severity Scale in the Study Eye Over Time, Treatment-Naive Population Week 96	23.9 Percentage of participants Interval 17.3 to 30.5	17.1 Percentage of participants Interval 11.5 to 22.6	25.3 Percentage of participants Interval 18.9 to 31.6

SECONDARY outcome

Timeframe: Baseline, Weeks 16, 52, and 96

The Early Treatment Diabetic Retinopathy Study (ETDRS) Diabetic Retinopathy Severity Scale (DRSS) classifies diabetic retinopathy into 12 severity steps ranging from absence of retinopathy to advanced proliferative diabetic retinopathy. Ocular imaging assessments were made independently by a central reading center. The weighted estimates of the percentage of participants were based on the Cochran-Mantel Haenszel (CMH) weights stratified by baseline BCVA (≥64 vs. \<64 letters), prior IVT anti-VEGF therapy (yes vs. no), and region (U.S. and Canada vs. rest of the world; Asia and rest of the world regions were combined). Treatment policy strategy (i.e., all observed values used) and hypothetical strategy (i.e., all values censored after the occurrence of the intercurrent event) were applied to non-COVID-19 related and COVID-19 related intercurrent events, respectively. Missing data were not imputed. 95% confidence interval (CI) is a rounding of 95.04% CI.

Outcome measures

Outcome measures
Measure	A: Faricimab 6 mg Q8W n=315 Participants Participants randomized to Arm A received 6 milligrams (mg) faricimab intravitreal (IVT) injections once every 4 weeks (Q4W) to Week 20, followed by 6 mg faricimab IVT injections once every 8 weeks (Q8W) to Week 96, followed by the final study visit at Week 100.	B: Faricimab 6 mg PTI n=313 Participants Participants randomized to Arm B received 6 milligrams (mg) faricimab intravitreal (IVT) injections Q4W to at least Week 12, followed by a personalized treatment interval (PTI) dosing of 6 mg faricimab IVT injections up to once every 16 weeks (Q16W) through Week 96, followed by the final study visit at Week 100.	C: Aflibercept 2 mg Q8W n=312 Participants Participants randomized to Arm C received 2 milligrams (mg) aflibercept intravitreal (IVT) injections Q4W to Week 16, followed by 2 mg aflibercept IVT injections Q8W to Week 96, followed by the final study visit at Week 100.
Percentage of Participants With a ≥4-Step Diabetic Retinopathy Severity Improvement From Baseline on the ETDRS Diabetic Retinopathy Severity Scale in the Study Eye Over Time, ITT Population Week 16	3.6 Percentage of participants Interval 1.4 to 5.8	3.5 Percentage of participants Interval 1.4 to 5.6	3.9 Percentage of participants Interval 1.7 to 6.2
Percentage of Participants With a ≥4-Step Diabetic Retinopathy Severity Improvement From Baseline on the ETDRS Diabetic Retinopathy Severity Scale in the Study Eye Over Time, ITT Population Week 52	5.8 Percentage of participants Interval 2.9 to 8.7	4.9 Percentage of participants Interval 2.2 to 7.7	4.5 Percentage of participants Interval 1.9 to 7.0
Percentage of Participants With a ≥4-Step Diabetic Retinopathy Severity Improvement From Baseline on the ETDRS Diabetic Retinopathy Severity Scale in the Study Eye Over Time, ITT Population Week 96	5.9 Percentage of participants Interval 2.8 to 9.0	5.8 Percentage of participants Interval 2.8 to 8.8	6.0 Percentage of participants Interval 3.0 to 9.0

SECONDARY outcome

Timeframe: Baseline, Weeks 16, 52, and 96

Population: Treatment-Naive Population: all participants randomized in the study who had not received any intravitreal anti-VEGF agents in the study eye prior to randomization. Participants were grouped according to the treatment assigned at randomization. Only participants with non-missing, valid assessments at Baseline and each timepoint were included in the analysis.

The Early Treatment Diabetic Retinopathy Study (ETDRS) Diabetic Retinopathy Severity Scale (DRSS) classifies diabetic retinopathy into 12 severity steps ranging from absence of retinopathy to advanced proliferative diabetic retinopathy. Ocular imaging assessments were made independently by a central reading center. The weighted estimates of the percentage of participants were based on the Cochran-Mantel Haenszel (CMH) weights stratified by baseline BCVA (≥64 vs. \<64 letters) and region (U.S. and Canada vs. rest of the world; Asia and rest of the world regions were combined). Treatment policy strategy (i.e., all observed values used) and hypothetical strategy (i.e., all values censored after the occurrence of the intercurrent event) were applied to non-COVID-19 related and COVID-19 related intercurrent events, respectively. Missing data were not imputed. 95% confidence interval (CI) is a rounding of 95.04% CI.

Outcome measures

Outcome measures
Measure	A: Faricimab 6 mg Q8W n=238 Participants Participants randomized to Arm A received 6 milligrams (mg) faricimab intravitreal (IVT) injections once every 4 weeks (Q4W) to Week 20, followed by 6 mg faricimab IVT injections once every 8 weeks (Q8W) to Week 96, followed by the final study visit at Week 100.	B: Faricimab 6 mg PTI n=245 Participants Participants randomized to Arm B received 6 milligrams (mg) faricimab intravitreal (IVT) injections Q4W to at least Week 12, followed by a personalized treatment interval (PTI) dosing of 6 mg faricimab IVT injections up to once every 16 weeks (Q16W) through Week 96, followed by the final study visit at Week 100.	C: Aflibercept 2 mg Q8W n=242 Participants Participants randomized to Arm C received 2 milligrams (mg) aflibercept intravitreal (IVT) injections Q4W to Week 16, followed by 2 mg aflibercept IVT injections Q8W to Week 96, followed by the final study visit at Week 100.
Percentage of Participants With a ≥4-Step Diabetic Retinopathy Severity Improvement From Baseline on the ETDRS Diabetic Retinopathy Severity Scale in the Study Eye Over Time, Treatment-Naive Population Week 16	3.9 Percentage of participants Interval 1.3 to 6.4	3.5 Percentage of participants Interval 1.1 to 5.9	3.6 Percentage of participants Interval 1.2 to 6.1
Percentage of Participants With a ≥4-Step Diabetic Retinopathy Severity Improvement From Baseline on the ETDRS Diabetic Retinopathy Severity Scale in the Study Eye Over Time, Treatment-Naive Population Week 52	6.2 Percentage of participants Interval 2.7 to 9.7	5.1 Percentage of participants Interval 2.0 to 8.3	4.2 Percentage of participants Interval 1.4 to 7.0
Percentage of Participants With a ≥4-Step Diabetic Retinopathy Severity Improvement From Baseline on the ETDRS Diabetic Retinopathy Severity Scale in the Study Eye Over Time, Treatment-Naive Population Week 96	7.0 Percentage of participants Interval 3.0 to 11.0	6.8 Percentage of participants Interval 3.1 to 10.5	6.3 Percentage of participants Interval 2.8 to 9.8

SECONDARY outcome

Timeframe: Baseline and Week 52

Population: ITT Population and Treatment-Naive Population. Only participants with non-missing, valid assessments at Baseline and Week 52 were included in the analysis.

The Early Treatment Diabetic Retinopathy Study (ETDRS) Diabetic Retinopathy Severity Scale (DRSS) classifies diabetic retinopathy into 12 severity steps ranging from absence of retinopathy to advanced proliferative diabetic retinopathy (PDR). PDR was defined as an ETDRS DRSS score of ≥61 on the 7-field/4-wide field color fundus photographs assessment by a central reading center. The weighted percentages of participants were based on the Cochran-Mantel Haenszel (CMH) weights stratified by baseline BCVA (≥64 vs. \<64 letters), prior IVT anti-VEGF therapy (yes vs. no), and region (U.S. and Canada vs. rest of the world; Asia and rest of the world regions were combined). Treatment policy strategy (i.e., all observed values used) and hypothetical strategy (i.e., all values censored after the occurrence of the intercurrent event) were applied to non-COVID-19 related and COVID-19 related intercurrent events, respectively. Missing data were not imputed. 95% CI is a rounding of 95.04% CI.

Outcome measures

Outcome measures
Measure	A: Faricimab 6 mg Q8W n=219 Participants Participants randomized to Arm A received 6 milligrams (mg) faricimab intravitreal (IVT) injections once every 4 weeks (Q4W) to Week 20, followed by 6 mg faricimab IVT injections once every 8 weeks (Q8W) to Week 96, followed by the final study visit at Week 100.	B: Faricimab 6 mg PTI n=224 Participants Participants randomized to Arm B received 6 milligrams (mg) faricimab intravitreal (IVT) injections Q4W to at least Week 12, followed by a personalized treatment interval (PTI) dosing of 6 mg faricimab IVT injections up to once every 16 weeks (Q16W) through Week 96, followed by the final study visit at Week 100.	C: Aflibercept 2 mg Q8W n=214 Participants Participants randomized to Arm C received 2 milligrams (mg) aflibercept intravitreal (IVT) injections Q4W to Week 16, followed by 2 mg aflibercept IVT injections Q8W to Week 96, followed by the final study visit at Week 100.
Percentage of Participants Without Proliferative Diabetic Retinopathy (PDR) at Baseline Who Developed New PDR at Week 52, ITT and Treatment-Naive Populations ITT Population	0.9 Percentage of participants Interval 0.0 to 2.2	0.9 Percentage of participants Interval 0.0 to 2.2	0.5 Percentage of participants Interval 0.0 to 1.4
Percentage of Participants Without Proliferative Diabetic Retinopathy (PDR) at Baseline Who Developed New PDR at Week 52, ITT and Treatment-Naive Populations Treatment-Naive Population	0.0 Percentage of participants Interval 0.0 to 0.0	1.2 Percentage of participants Interval 0.0 to 2.8	0.6 Percentage of participants Interval 0.0 to 1.9

SECONDARY outcome

Timeframe: Baseline and Week 52

Population: ITT Population and Treatment-Naive Population. Only participants with non-missing, valid assessments at Baseline and Week 52 were included in the analysis.

The Early Treatment Diabetic Retinopathy Study (ETDRS) Diabetic Retinopathy Severity Scale (DRSS) classifies diabetic retinopathy into 12 severity steps ranging from absence of retinopathy to advanced PDR. High-risk PDR was defined as an ETDRS DRSS score of ≥71 on the 7-field/4-wide field color fundus photographs assessment by a central reading center. The weighted estimates of the percentage of participants were based on the Cochran-Mantel Haenszel (CMH) weights stratified by baseline BCVA (≥64 vs. \<64 letters), prior IVT anti-VEGF therapy (yes vs. no), and region (U.S. and Canada vs. rest of the world; Asia and rest of the world regions were combined). Treatment policy strategy (i.e., all observed values used) and hypothetical strategy (i.e., all values censored after the occurrence of the intercurrent event) were applied to non-COVID-19 related and COVID-19 related intercurrent events, respectively. Missing data were not imputed. 95% CI is a rounding of 95.04% CI.

Outcome measures

Outcome measures
Measure	A: Faricimab 6 mg Q8W n=237 Participants Participants randomized to Arm A received 6 milligrams (mg) faricimab intravitreal (IVT) injections once every 4 weeks (Q4W) to Week 20, followed by 6 mg faricimab IVT injections once every 8 weeks (Q8W) to Week 96, followed by the final study visit at Week 100.	B: Faricimab 6 mg PTI n=241 Participants Participants randomized to Arm B received 6 milligrams (mg) faricimab intravitreal (IVT) injections Q4W to at least Week 12, followed by a personalized treatment interval (PTI) dosing of 6 mg faricimab IVT injections up to once every 16 weeks (Q16W) through Week 96, followed by the final study visit at Week 100.	C: Aflibercept 2 mg Q8W n=227 Participants Participants randomized to Arm C received 2 milligrams (mg) aflibercept intravitreal (IVT) injections Q4W to Week 16, followed by 2 mg aflibercept IVT injections Q8W to Week 96, followed by the final study visit at Week 100.
Percentage of Participants Without High-Risk Proliferative Diabetic Retinopathy (PDR) at Baseline Who Developed High-Risk PDR at Week 52, ITT and Treatment-Naive Populations ITT Population	0.4 Percentage of participants Interval 0.0 to 1.2	0.0 Percentage of participants Interval 0.0 to 0.0	0.0 Percentage of participants Interval 0.0 to 0.0
Percentage of Participants Without High-Risk Proliferative Diabetic Retinopathy (PDR) at Baseline Who Developed High-Risk PDR at Week 52, ITT and Treatment-Naive Populations Treatment-Naive Population	0.0 Percentage of participants Interval 0.0 to 0.0	0.0 Percentage of participants Interval 0.0 to 0.0	0.0 Percentage of participants Interval 0.0 to 0.0

SECONDARY outcome

Timeframe: Week 52

Population: ITT Population: all participants who were randomized in the study, grouped according to the treatment assigned at randomization. The number analyzed includes all participants in Arm B: Faricimab 6 mg PTI who had not discontinued the study prior to Week 52.

Outcome measures

Outcome measures
Measure	A: Faricimab 6 mg Q8W n=286 Participants Participants randomized to Arm A received 6 milligrams (mg) faricimab intravitreal (IVT) injections once every 4 weeks (Q4W) to Week 20, followed by 6 mg faricimab IVT injections once every 8 weeks (Q8W) to Week 96, followed by the final study visit at Week 100.	B: Faricimab 6 mg PTI Participants randomized to Arm B received 6 milligrams (mg) faricimab intravitreal (IVT) injections Q4W to at least Week 12, followed by a personalized treatment interval (PTI) dosing of 6 mg faricimab IVT injections up to once every 16 weeks (Q16W) through Week 96, followed by the final study visit at Week 100.	C: Aflibercept 2 mg Q8W Participants randomized to Arm C received 2 milligrams (mg) aflibercept intravitreal (IVT) injections Q4W to Week 16, followed by 2 mg aflibercept IVT injections Q8W to Week 96, followed by the final study visit at Week 100.
Percentage of Participants in the Faricimab 6 mg PTI Arm on a Once Every 4-Weeks, 8-Weeks, 12-Weeks, or 16-Weeks Treatment Interval at Week 52, ITT Population Once Every 4 Weeks	10.8 Percentage of participants Interval 7.2 to 14.4	—	—
Percentage of Participants in the Faricimab 6 mg PTI Arm on a Once Every 4-Weeks, 8-Weeks, 12-Weeks, or 16-Weeks Treatment Interval at Week 52, ITT Population Once Every 8 Weeks	15.4 Percentage of participants Interval 11.2 to 19.6	—	—
Percentage of Participants in the Faricimab 6 mg PTI Arm on a Once Every 4-Weeks, 8-Weeks, 12-Weeks, or 16-Weeks Treatment Interval at Week 52, ITT Population Once Every 12 Weeks	21.0 Percentage of participants Interval 16.3 to 25.7	—	—
Percentage of Participants in the Faricimab 6 mg PTI Arm on a Once Every 4-Weeks, 8-Weeks, 12-Weeks, or 16-Weeks Treatment Interval at Week 52, ITT Population Once Every 16 Weeks	52.8 Percentage of participants Interval 47.0 to 58.6	—	—

SECONDARY outcome

Timeframe: Week 52

Population: Treatment-Naive Population: all participants randomized in the study who had not received any intravitreal anti-VEGF agents in the study eye prior to randomization. Participants were grouped according to the treatment assigned at randomization. The number analyzed includes all participants in Arm B: Faricimab 6 mg PTI who had not discontinued the study prior to Week 52.

Outcome measures

Outcome measures
Measure	A: Faricimab 6 mg Q8W n=222 Participants Participants randomized to Arm A received 6 milligrams (mg) faricimab intravitreal (IVT) injections once every 4 weeks (Q4W) to Week 20, followed by 6 mg faricimab IVT injections once every 8 weeks (Q8W) to Week 96, followed by the final study visit at Week 100.	B: Faricimab 6 mg PTI Participants randomized to Arm B received 6 milligrams (mg) faricimab intravitreal (IVT) injections Q4W to at least Week 12, followed by a personalized treatment interval (PTI) dosing of 6 mg faricimab IVT injections up to once every 16 weeks (Q16W) through Week 96, followed by the final study visit at Week 100.	C: Aflibercept 2 mg Q8W Participants randomized to Arm C received 2 milligrams (mg) aflibercept intravitreal (IVT) injections Q4W to Week 16, followed by 2 mg aflibercept IVT injections Q8W to Week 96, followed by the final study visit at Week 100.
Percentage of Participants in the Faricimab 6 mg PTI Arm on a Once Every 4-Weeks, 8-Weeks, 12-Weeks, or 16-Weeks Treatment Interval at Week 52, Treatment-Naive Population Once Every 4 Weeks	9.0 Percentage of participants Interval 5.2 to 12.8	—	—
Percentage of Participants in the Faricimab 6 mg PTI Arm on a Once Every 4-Weeks, 8-Weeks, 12-Weeks, or 16-Weeks Treatment Interval at Week 52, Treatment-Naive Population Once Every 8 Weeks	14.4 Percentage of participants Interval 9.8 to 19.0	—	—
Percentage of Participants in the Faricimab 6 mg PTI Arm on a Once Every 4-Weeks, 8-Weeks, 12-Weeks, or 16-Weeks Treatment Interval at Week 52, Treatment-Naive Population Once Every 12 Weeks	22.1 Percentage of participants Interval 16.6 to 27.5	—	—
Percentage of Participants in the Faricimab 6 mg PTI Arm on a Once Every 4-Weeks, 8-Weeks, 12-Weeks, or 16-Weeks Treatment Interval at Week 52, Treatment-Naive Population Once Every 16 Weeks	54.5 Percentage of participants Interval 47.9 to 61.1	—	—

SECONDARY outcome

Timeframe: Week 96

Outcome measures

Outcome measures
Measure	A: Faricimab 6 mg Q8W n=270 Participants Participants randomized to Arm A received 6 milligrams (mg) faricimab intravitreal (IVT) injections once every 4 weeks (Q4W) to Week 20, followed by 6 mg faricimab IVT injections once every 8 weeks (Q8W) to Week 96, followed by the final study visit at Week 100.	B: Faricimab 6 mg PTI Participants randomized to Arm B received 6 milligrams (mg) faricimab intravitreal (IVT) injections Q4W to at least Week 12, followed by a personalized treatment interval (PTI) dosing of 6 mg faricimab IVT injections up to once every 16 weeks (Q16W) through Week 96, followed by the final study visit at Week 100.	C: Aflibercept 2 mg Q8W Participants randomized to Arm C received 2 milligrams (mg) aflibercept intravitreal (IVT) injections Q4W to Week 16, followed by 2 mg aflibercept IVT injections Q8W to Week 96, followed by the final study visit at Week 100.
Percentage of Participants in the Faricimab 6 mg PTI Arm on a Once Every 4-Weeks, 8-Weeks, 12-Weeks, or 16-Weeks Treatment Interval at Week 96, ITT Population Once Every 4 Weeks	7.0 Percentage of participants Interval 4.0 to 10.1	—	—
Percentage of Participants in the Faricimab 6 mg PTI Arm on a Once Every 4-Weeks, 8-Weeks, 12-Weeks, or 16-Weeks Treatment Interval at Week 96, ITT Population Once Every 8 Weeks	14.8 Percentage of participants Interval 10.6 to 19.1	—	—
Percentage of Participants in the Faricimab 6 mg PTI Arm on a Once Every 4-Weeks, 8-Weeks, 12-Weeks, or 16-Weeks Treatment Interval at Week 96, ITT Population Once Every 12 Weeks	18.1 Percentage of participants Interval 13.5 to 22.8	—	—
Percentage of Participants in the Faricimab 6 mg PTI Arm on a Once Every 4-Weeks, 8-Weeks, 12-Weeks, or 16-Weeks Treatment Interval at Week 96, ITT Population Once Every 16 Weeks	60.0 Percentage of participants Interval 54.1 to 65.9	—	—

SECONDARY outcome

Timeframe: Week 96

Population: Treatment-Naive Population: all participants randomized in the study who had not received any intravitreal anti-VEGF agents in the study eye prior to randomization. Participants were grouped according to the treatment assigned at randomization. The number analyzed includes all participants in Arm B: Faricimab 6 mg PTI who had not discontinued the study prior to Week 96.

Outcome measures

Outcome measures
Measure	A: Faricimab 6 mg Q8W n=208 Participants Participants randomized to Arm A received 6 milligrams (mg) faricimab intravitreal (IVT) injections once every 4 weeks (Q4W) to Week 20, followed by 6 mg faricimab IVT injections once every 8 weeks (Q8W) to Week 96, followed by the final study visit at Week 100.	B: Faricimab 6 mg PTI Participants randomized to Arm B received 6 milligrams (mg) faricimab intravitreal (IVT) injections Q4W to at least Week 12, followed by a personalized treatment interval (PTI) dosing of 6 mg faricimab IVT injections up to once every 16 weeks (Q16W) through Week 96, followed by the final study visit at Week 100.	C: Aflibercept 2 mg Q8W Participants randomized to Arm C received 2 milligrams (mg) aflibercept intravitreal (IVT) injections Q4W to Week 16, followed by 2 mg aflibercept IVT injections Q8W to Week 96, followed by the final study visit at Week 100.
Percentage of Participants in the Faricimab 6 mg PTI Arm on a Once Every 4-Weeks, 8-Weeks, 12-Weeks, or 16-Weeks Treatment Interval at Week 96, Treatment-Naive Population Once Every 8 Weeks	11.1 Percentage of participants Interval 6.8 to 15.3	—	—
Percentage of Participants in the Faricimab 6 mg PTI Arm on a Once Every 4-Weeks, 8-Weeks, 12-Weeks, or 16-Weeks Treatment Interval at Week 96, Treatment-Naive Population Once Every 4 Weeks	7.2 Percentage of participants Interval 3.7 to 10.7	—	—
Percentage of Participants in the Faricimab 6 mg PTI Arm on a Once Every 4-Weeks, 8-Weeks, 12-Weeks, or 16-Weeks Treatment Interval at Week 96, Treatment-Naive Population Once Every 12 Weeks	16.8 Percentage of participants Interval 11.7 to 21.9	—	—
Percentage of Participants in the Faricimab 6 mg PTI Arm on a Once Every 4-Weeks, 8-Weeks, 12-Weeks, or 16-Weeks Treatment Interval at Week 96, Treatment-Naive Population Once Every 16 Weeks	64.9 Percentage of participants Interval 58.4 to 71.4	—	—

SECONDARY outcome

Timeframe: From start of PTI (Week 12 or later) until Week 52

Population: ITT Population and Treatment-Naive Population. The number analyzed includes all participants in Arm B: Faricimab 6 mg PTI who had not discontinued the study prior to Week 52.

Outcome measures

Outcome measures
Measure	A: Faricimab 6 mg Q8W n=286 Participants Participants randomized to Arm A received 6 milligrams (mg) faricimab intravitreal (IVT) injections once every 4 weeks (Q4W) to Week 20, followed by 6 mg faricimab IVT injections once every 8 weeks (Q8W) to Week 96, followed by the final study visit at Week 100.	B: Faricimab 6 mg PTI Participants randomized to Arm B received 6 milligrams (mg) faricimab intravitreal (IVT) injections Q4W to at least Week 12, followed by a personalized treatment interval (PTI) dosing of 6 mg faricimab IVT injections up to once every 16 weeks (Q16W) through Week 96, followed by the final study visit at Week 100.	C: Aflibercept 2 mg Q8W Participants randomized to Arm C received 2 milligrams (mg) aflibercept intravitreal (IVT) injections Q4W to Week 16, followed by 2 mg aflibercept IVT injections Q8W to Week 96, followed by the final study visit at Week 100.
Percentage of Participants in the Faricimab 6 mg PTI Arm at Week 52 Who Achieved a Once Every 12-Weeks or 16-Weeks Treatment Interval Without an Interval Decrease Below Once Every 12 Weeks, ITT and Treatment-Naive Populations ITT Population	67.8 Percentage of participants Interval 62.4 to 73.3	—	—
Percentage of Participants in the Faricimab 6 mg PTI Arm at Week 52 Who Achieved a Once Every 12-Weeks or 16-Weeks Treatment Interval Without an Interval Decrease Below Once Every 12 Weeks, ITT and Treatment-Naive Populations Treatment-Naive Population	71.6 Percentage of participants Interval 65.7 to 77.6	—	—

SECONDARY outcome

Timeframe: From start of PTI (Week 12 or later) until Week 96

Population: ITT Population and Treatment-Naive Population. The number analyzed includes all participants in Arm B: Faricimab 6 mg PTI who had not discontinued the study prior to Week 96.

Outcome measures

Outcome measures
Measure	A: Faricimab 6 mg Q8W n=270 Participants Participants randomized to Arm A received 6 milligrams (mg) faricimab intravitreal (IVT) injections once every 4 weeks (Q4W) to Week 20, followed by 6 mg faricimab IVT injections once every 8 weeks (Q8W) to Week 96, followed by the final study visit at Week 100.	B: Faricimab 6 mg PTI Participants randomized to Arm B received 6 milligrams (mg) faricimab intravitreal (IVT) injections Q4W to at least Week 12, followed by a personalized treatment interval (PTI) dosing of 6 mg faricimab IVT injections up to once every 16 weeks (Q16W) through Week 96, followed by the final study visit at Week 100.	C: Aflibercept 2 mg Q8W Participants randomized to Arm C received 2 milligrams (mg) aflibercept intravitreal (IVT) injections Q4W to Week 16, followed by 2 mg aflibercept IVT injections Q8W to Week 96, followed by the final study visit at Week 100.
Percentage of Participants in the Faricimab 6 mg PTI Arm at Week 96 Who Achieved a Once Every 12-Weeks or 16-Weeks Treatment Interval Without an Interval Decrease Below Once Every 12 Weeks, ITT and Treatment-Naive Populations ITT Population	60.4 Percentage of participants Interval 54.5 to 66.2	—	—
Percentage of Participants in the Faricimab 6 mg PTI Arm at Week 96 Who Achieved a Once Every 12-Weeks or 16-Weeks Treatment Interval Without an Interval Decrease Below Once Every 12 Weeks, ITT and Treatment-Naive Populations Treatment-Naive Population	64.4 Percentage of participants Interval 57.9 to 70.9	—	—

SECONDARY outcome

Timeframe: From Baseline through Week 56

Population: ITT Population and Treatment-Naive Population

Central subfield thickness (CST) was defined as the distance between the internal limiting membrane (ILM) and Bruch's membrane (BM) as assessed by a central reading center. For the Mixed Model for Repeated Measures (MMRM) analysis, the model adjusted for treatment group, visit, visit-by-treatment group interaction, baseline CST (continuous), baseline BCVA (\<64 vs. ≥64 letters), prior intravitreal anti-VEGF therapy (yes vs. no), and region of enrollment (U.S. and Canada vs. the rest of the world; Asia and rest of the world regions were combined). An unstructured covariance structure was used. Treatment policy strategy (i.e., all observed values used) and hypothetical strategy (i.e., all values censored after the occurrence of the intercurrent event) were applied to non-COVID-19 related and COVID-19 related intercurrent events, respectively. Missing data were implicitly imputed by MMRM. 95% confidence interval (CI) is a rounding of 95.04% CI.

Outcome measures

Outcome measures
Measure	A: Faricimab 6 mg Q8W n=315 Participants Participants randomized to Arm A received 6 milligrams (mg) faricimab intravitreal (IVT) injections once every 4 weeks (Q4W) to Week 20, followed by 6 mg faricimab IVT injections once every 8 weeks (Q8W) to Week 96, followed by the final study visit at Week 100.	B: Faricimab 6 mg PTI n=313 Participants Participants randomized to Arm B received 6 milligrams (mg) faricimab intravitreal (IVT) injections Q4W to at least Week 12, followed by a personalized treatment interval (PTI) dosing of 6 mg faricimab IVT injections up to once every 16 weeks (Q16W) through Week 96, followed by the final study visit at Week 100.	C: Aflibercept 2 mg Q8W n=312 Participants Participants randomized to Arm C received 2 milligrams (mg) aflibercept intravitreal (IVT) injections Q4W to Week 16, followed by 2 mg aflibercept IVT injections Q8W to Week 96, followed by the final study visit at Week 100.
Change From Baseline in Central Subfield Thickness in the Study Eye Averaged Over Weeks 48, 52, and 56, ITT and Treatment-Naive Populations ITT Population	-206.6 microns Interval -214.7 to -198.4	-196.5 microns Interval -204.7 to -188.4	-170.3 microns Interval -178.5 to -162.2
Change From Baseline in Central Subfield Thickness in the Study Eye Averaged Over Weeks 48, 52, and 56, ITT and Treatment-Naive Populations Treatment-Naive Population	-204.6 microns Interval -213.5 to -195.7	-197.5 microns Interval -206.2 to -188.8	-173.6 microns Interval -182.3 to -164.8

SECONDARY outcome

Timeframe: Baseline, Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, 56, 60, 64, 68, 72, 76, 80, 84, 88, 92, 96, and 100

Population: ITT Population: all participants who were randomized in the study, grouped according to the treatment assigned at randomization.

Outcome measures

Outcome measures
Measure	A: Faricimab 6 mg Q8W n=315 Participants Participants randomized to Arm A received 6 milligrams (mg) faricimab intravitreal (IVT) injections once every 4 weeks (Q4W) to Week 20, followed by 6 mg faricimab IVT injections once every 8 weeks (Q8W) to Week 96, followed by the final study visit at Week 100.	B: Faricimab 6 mg PTI n=313 Participants Participants randomized to Arm B received 6 milligrams (mg) faricimab intravitreal (IVT) injections Q4W to at least Week 12, followed by a personalized treatment interval (PTI) dosing of 6 mg faricimab IVT injections up to once every 16 weeks (Q16W) through Week 96, followed by the final study visit at Week 100.	C: Aflibercept 2 mg Q8W n=312 Participants Participants randomized to Arm C received 2 milligrams (mg) aflibercept intravitreal (IVT) injections Q4W to Week 16, followed by 2 mg aflibercept IVT injections Q8W to Week 96, followed by the final study visit at Week 100.
Change From Baseline in Central Subfield Thickness in the Study Eye Over Time, ITT Population Week 4	-118.4 microns Interval -128.5 to -108.2	-124.9 microns Interval -135.0 to -114.8	-111.0 microns Interval -121.2 to -100.8
Change From Baseline in Central Subfield Thickness in the Study Eye Over Time, ITT Population Week 8	-145.9 microns Interval -155.2 to -136.5	-149.6 microns Interval -159.0 to -140.3	-130.9 microns Interval -140.4 to -121.5
Change From Baseline in Central Subfield Thickness in the Study Eye Over Time, ITT Population Week 12	-165.6 microns Interval -174.3 to -156.9	-168.4 microns Interval -177.1 to -159.8	-144.7 microns Interval -153.4 to -136.0
Change From Baseline in Central Subfield Thickness in the Study Eye Over Time, ITT Population Week 16	-177.6 microns Interval -186.0 to -169.2	-182.1 microns Interval -190.4 to -173.7	-152.7 microns Interval -161.1 to -144.3
Change From Baseline in Central Subfield Thickness in the Study Eye Over Time, ITT Population Week 20	-184.6 microns Interval -193.2 to -176.1	-174.6 microns Interval -183.1 to -166.0	-159.0 microns Interval -167.6 to -150.4
Change From Baseline in Central Subfield Thickness in the Study Eye Over Time, ITT Population Week 24	-196.4 microns Interval -204.8 to -188.0	-192.8 microns Interval -201.2 to -184.3	-146.3 microns Interval -154.7 to -137.8
Change From Baseline in Central Subfield Thickness in the Study Eye Over Time, ITT Population Week 28	-174.6 microns Interval -184.4 to -164.9	-193.7 microns Interval -203.4 to -184.0	-163.8 microns Interval -173.6 to -154.0
Change From Baseline in Central Subfield Thickness in the Study Eye Over Time, ITT Population Week 32	-200.2 microns Interval -209.4 to -191.0	-181.6 microns Interval -190.8 to -172.4	-147.2 microns Interval -156.4 to -138.0
Change From Baseline in Central Subfield Thickness in the Study Eye Over Time, ITT Population Week 36	-179.4 microns Interval -188.9 to -169.8	-201.0 microns Interval -210.6 to -191.5	-166.0 microns Interval -175.7 to -156.4
Change From Baseline in Central Subfield Thickness in the Study Eye Over Time, ITT Population Week 40	-205.1 microns Interval -214.5 to -195.7	-193.5 microns Interval -203.0 to -184.1	-153.9 microns Interval -163.4 to -144.4
Change From Baseline in Central Subfield Thickness in the Study Eye Over Time, ITT Population Week 44	-187.5 microns Interval -197.4 to -177.5	-189.2 microns Interval -199.1 to -179.3	-172.6 microns Interval -182.6 to -162.6
Change From Baseline in Central Subfield Thickness in the Study Eye Over Time, ITT Population Week 48	-209.7 microns Interval -218.6 to -200.8	-194.8 microns Interval -203.7 to -185.8	-163.2 microns Interval -172.2 to -154.3
Change From Baseline in Central Subfield Thickness in the Study Eye Over Time, ITT Population Week 52	-191.0 microns Interval -200.6 to -181.4	-193.0 microns Interval -202.6 to -183.4	-179.2 microns Interval -188.9 to -169.5
Change From Baseline in Central Subfield Thickness in the Study Eye Over Time, ITT Population Week 56	-212.4 microns Interval -221.5 to -203.4	-200.3 microns Interval -209.3 to -191.2	-164.4 microns Interval -173.5 to -155.2
Change From Baseline in Central Subfield Thickness in the Study Eye Over Time, ITT Population Week 60	-197.8 microns Interval -207.4 to -188.2	-196.3 microns Interval -205.9 to -186.6	-182.0 microns Interval -191.7 to -172.3
Change From Baseline in Central Subfield Thickness in the Study Eye Over Time, ITT Population Week 64	-214.9 microns Interval -224.0 to -205.9	-199.9 microns Interval -208.9 to -190.8	-171.5 microns Interval -180.6 to -162.4
Change From Baseline in Central Subfield Thickness in the Study Eye Over Time, ITT Population Week 68	-201.1 microns Interval -210.0 to -192.3	-200.9 microns Interval -209.7 to -192.1	-186.8 microns Interval -195.7 to -177.9
Change From Baseline in Central Subfield Thickness in the Study Eye Over Time, ITT Population Week 72	-216.2 microns Interval -224.9 to -207.6	-201.6 microns Interval -210.3 to -193.0	-182.3 microns Interval -191.1 to -173.6
Change From Baseline in Central Subfield Thickness in the Study Eye Over Time, ITT Population Week 76	-206.0 microns Interval -215.1 to -197.0	-200.7 microns Interval -209.8 to -191.7	-188.4 microns Interval -197.6 to -179.3
Change From Baseline in Central Subfield Thickness in the Study Eye Over Time, ITT Population Week 80	-219.1 microns Interval -227.7 to -210.5	-203.2 microns Interval -211.7 to -194.6	-184.5 microns Interval -193.2 to -175.9
Change From Baseline in Central Subfield Thickness in the Study Eye Over Time, ITT Population Week 84	-211.8 microns Interval -221.1 to -202.5	-204.9 microns Interval -214.1 to -195.7	-186.2 microns Interval -195.5 to -176.9
Change From Baseline in Central Subfield Thickness in the Study Eye Over Time, ITT Population Week 88	-218.6 microns Interval -228.0 to -209.3	-204.1 microns Interval -213.4 to -194.8	-183.7 microns Interval -193.1 to -174.3
Change From Baseline in Central Subfield Thickness in the Study Eye Over Time, ITT Population Week 92	-210.9 microns Interval -220.1 to -201.7	-202.4 microns Interval -211.4 to -193.3	-193.9 microns Interval -203.2 to -184.7
Change From Baseline in Central Subfield Thickness in the Study Eye Over Time, ITT Population Week 96	-224.0 microns Interval -232.9 to -215.1	-203.8 microns Interval -212.6 to -195.1	-194.7 microns Interval -203.6 to -185.8
Change From Baseline in Central Subfield Thickness in the Study Eye Over Time, ITT Population Week 100	-213.1 microns Interval -221.8 to -204.3	-207.3 microns Interval -216.0 to -198.6	-200.2 microns Interval -209.0 to -191.4

SECONDARY outcome

Timeframe: Baseline, Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, 56, 60, 64, 68, 72, 76, 80, 84, 88, 92, 96, and 100

Central subfield thickness (CST) was defined as the distance between the internal limiting membrane (ILM) and Bruch's membrane (BM) as assessed by a central reading center. For the Mixed Model for Repeated Measures (MMRM) analysis, the model adjusted for treatment group, visit, visit-by-treatment group interaction, baseline CST (continuous), baseline BCVA (\<64 vs. ≥64 letters), and region of enrollment (U.S. and Canada vs. the rest of the world; Asia and rest of the world regions were combined). An unstructured covariance structure was used. Treatment policy strategy (i.e., all observed values used) and hypothetical strategy (i.e., all values censored after the occurrence of the intercurrent event) were applied to non-COVID-19 related and COVID-19 related intercurrent events, respectively. Missing data were implicitly imputed by MMRM. 95% confidence interval (CI) is a rounding of 95.04% CI.

Outcome measures

Outcome measures
Measure	A: Faricimab 6 mg Q8W n=238 Participants Participants randomized to Arm A received 6 milligrams (mg) faricimab intravitreal (IVT) injections once every 4 weeks (Q4W) to Week 20, followed by 6 mg faricimab IVT injections once every 8 weeks (Q8W) to Week 96, followed by the final study visit at Week 100.	B: Faricimab 6 mg PTI n=245 Participants Participants randomized to Arm B received 6 milligrams (mg) faricimab intravitreal (IVT) injections Q4W to at least Week 12, followed by a personalized treatment interval (PTI) dosing of 6 mg faricimab IVT injections up to once every 16 weeks (Q16W) through Week 96, followed by the final study visit at Week 100.	C: Aflibercept 2 mg Q8W n=242 Participants Participants randomized to Arm C received 2 milligrams (mg) aflibercept intravitreal (IVT) injections Q4W to Week 16, followed by 2 mg aflibercept IVT injections Q8W to Week 96, followed by the final study visit at Week 100.
Change From Baseline in Central Subfield Thickness in the Study Eye Over Time, Treatment-Naive Population Week 44	-187.3 microns Interval -198.5 to -176.1	-189.3 microns Interval -200.2 to -178.3	-172.9 microns Interval -184.0 to -161.8
Change From Baseline in Central Subfield Thickness in the Study Eye Over Time, Treatment-Naive Population Week 48	-207.3 microns Interval -217.3 to -197.3	-194.9 microns Interval -204.7 to -185.1	-165.0 microns Interval -174.9 to -155.1
Change From Baseline in Central Subfield Thickness in the Study Eye Over Time, Treatment-Naive Population Week 4	-116.1 microns Interval -127.0 to -105.2	-121.5 microns Interval -132.1 to -110.9	-110.1 microns Interval -120.9 to -99.3
Change From Baseline in Central Subfield Thickness in the Study Eye Over Time, Treatment-Naive Population Week 8	-142.9 microns Interval -153.0 to -132.8	-147.4 microns Interval -157.3 to -137.5	-131.5 microns Interval -141.5 to -121.5
Change From Baseline in Central Subfield Thickness in the Study Eye Over Time, Treatment-Naive Population Week 12	-162.8 microns Interval -171.9 to -153.6	-166.7 microns Interval -175.7 to -157.8	-147.4 microns Interval -156.4 to -138.3
Change From Baseline in Central Subfield Thickness in the Study Eye Over Time, Treatment-Naive Population Week 16	-175.1 microns Interval -183.8 to -166.3	-181.7 microns Interval -190.3 to -173.1	-155.9 microns Interval -164.5 to -147.2
Change From Baseline in Central Subfield Thickness in the Study Eye Over Time, Treatment-Naive Population Week 20	-182.9 microns Interval -192.0 to -173.8	-178.1 microns Interval -187.0 to -169.2	-161.6 microns Interval -170.6 to -152.6
Change From Baseline in Central Subfield Thickness in the Study Eye Over Time, Treatment-Naive Population Week 24	-194.2 microns Interval -203.4 to -184.9	-191.1 microns Interval -200.2 to -182.0	-149.7 microns Interval -158.9 to -140.6
Change From Baseline in Central Subfield Thickness in the Study Eye Over Time, Treatment-Naive Population Week 28	-177.4 microns Interval -188.1 to -166.7	-194.0 microns Interval -204.4 to -183.5	-167.5 microns Interval -178.0 to -156.9
Change From Baseline in Central Subfield Thickness in the Study Eye Over Time, Treatment-Naive Population Week 32	-196.4 microns Interval -206.6 to -186.2	-183.7 microns Interval -193.7 to -173.8	-150.2 microns Interval -160.3 to -140.2
Change From Baseline in Central Subfield Thickness in the Study Eye Over Time, Treatment-Naive Population Week 36	-181.9 microns Interval -191.9 to -171.9	-203.6 microns Interval -213.3 to -193.8	-168.7 microns Interval -178.6 to -158.9
Change From Baseline in Central Subfield Thickness in the Study Eye Over Time, Treatment-Naive Population Week 40	-198.9 microns Interval -209.7 to -188.1	-192.1 microns Interval -202.8 to -181.4	-157.4 microns Interval -168.2 to -146.5
Change From Baseline in Central Subfield Thickness in the Study Eye Over Time, Treatment-Naive Population Week 52	-191.1 microns Interval -201.7 to -180.5	-196.2 microns Interval -206.5 to -185.9	-181.1 microns Interval -191.6 to -170.5
Change From Baseline in Central Subfield Thickness in the Study Eye Over Time, Treatment-Naive Population Week 56	-210.4 microns Interval -220.0 to -200.8	-200.9 microns Interval -210.3 to -191.5	-171.0 microns Interval -180.6 to -161.4
Change From Baseline in Central Subfield Thickness in the Study Eye Over Time, Treatment-Naive Population Week 60	-195.0 microns Interval -205.6 to -184.4	-198.0 microns Interval -208.4 to -187.5	-185.1 microns Interval -195.6 to -174.5
Change From Baseline in Central Subfield Thickness in the Study Eye Over Time, Treatment-Naive Population Week 64	-213.7 microns Interval -223.5 to -203.9	-199.2 microns Interval -208.8 to -189.6	-175.3 microns Interval -184.9 to -165.6
Change From Baseline in Central Subfield Thickness in the Study Eye Over Time, Treatment-Naive Population Week 68	-201.5 microns Interval -211.2 to -191.7	-201.7 microns Interval -211.2 to -192.1	-189.1 microns Interval -198.8 to -179.5
Change From Baseline in Central Subfield Thickness in the Study Eye Over Time, Treatment-Naive Population Week 72	-215.9 microns Interval -225.5 to -206.4	-203.2 microns Interval -212.5 to -193.9	-184.1 microns Interval -193.5 to -174.6
Change From Baseline in Central Subfield Thickness in the Study Eye Over Time, Treatment-Naive Population Week 76	-204.8 microns Interval -214.8 to -194.9	-202.1 microns Interval -211.8 to -192.4	-189.8 microns Interval -199.7 to -180.0
Change From Baseline in Central Subfield Thickness in the Study Eye Over Time, Treatment-Naive Population Week 80	-217.3 microns Interval -227.0 to -207.5	-202.2 microns Interval -211.6 to -192.7	-186.2 microns Interval -195.9 to -176.6
Change From Baseline in Central Subfield Thickness in the Study Eye Over Time, Treatment-Naive Population Week 84	-211.0 microns Interval -221.6 to -200.4	-202.9 microns Interval -213.2 to -192.7	-185.7 microns Interval -196.1 to -175.2
Change From Baseline in Central Subfield Thickness in the Study Eye Over Time, Treatment-Naive Population Week 88	-215.9 microns Interval -226.4 to -205.5	-205.2 microns Interval -215.3 to -195.0	-186.4 microns Interval -196.7 to -176.1
Change From Baseline in Central Subfield Thickness in the Study Eye Over Time, Treatment-Naive Population Week 92	-208.8 microns Interval -218.9 to -198.7	-202.2 microns Interval -212.0 to -192.5	-195.9 microns Interval -205.9 to -186.0
Change From Baseline in Central Subfield Thickness in the Study Eye Over Time, Treatment-Naive Population Week 96	-221.0 microns Interval -231.4 to -210.7	-199.0 microns Interval -209.0 to -189.1	-196.7 microns Interval -206.9 to -186.6
Change From Baseline in Central Subfield Thickness in the Study Eye Over Time, Treatment-Naive Population Week 100	-213.4 microns Interval -222.7 to -204.1	-206.7 microns Interval -215.7 to -197.7	-201.3 microns Interval -210.5 to -192.1

SECONDARY outcome

Timeframe: Average of Weeks 48, 52, and 56

Population: ITT Population and Treatment-Naive Population. Only participants with at least one non-missing, valid assessment at Weeks 48, 52, or 56 were included in the analysis.

Absence of diabetic macular edema was defined as achieving a central subfield thickness (CST) of \<325 microns in the study eye. CST was defined as the distance between the internal limiting membrane and Bruch's membrane. For each participant, an average CST value was calculated across the three visits, and this averaged value was then used to determine if the endpoint was met. The results were summarized as the percentage of participants per treatment arm who met the endpoint. The weighted estimates of the percentage of participants were based on the Cochran-Mantel Haenszel (CMH) weights stratified by baseline BCVA (≥64 vs. \<64 letters), prior IVT anti-VEGF therapy (yes vs. no), and region (U.S. and Canada vs. rest of the world). Treatment policy strategy and hypothetical strategy were applied to non-COVID-19 related and COVID-19 related intercurrent events, respectively. Missing data were not imputed. 95% confidence interval (CI) is a rounding of 95.04% CI.

Outcome measures

Outcome measures
Measure	A: Faricimab 6 mg Q8W n=272 Participants Participants randomized to Arm A received 6 milligrams (mg) faricimab intravitreal (IVT) injections once every 4 weeks (Q4W) to Week 20, followed by 6 mg faricimab IVT injections once every 8 weeks (Q8W) to Week 96, followed by the final study visit at Week 100.	B: Faricimab 6 mg PTI n=276 Participants Participants randomized to Arm B received 6 milligrams (mg) faricimab intravitreal (IVT) injections Q4W to at least Week 12, followed by a personalized treatment interval (PTI) dosing of 6 mg faricimab IVT injections up to once every 16 weeks (Q16W) through Week 96, followed by the final study visit at Week 100.	C: Aflibercept 2 mg Q8W n=275 Participants Participants randomized to Arm C received 2 milligrams (mg) aflibercept intravitreal (IVT) injections Q4W to Week 16, followed by 2 mg aflibercept IVT injections Q8W to Week 96, followed by the final study visit at Week 100.
Percentage of Participants With Absence of Diabetic Macular Edema in the Study Eye Averaged Over Weeks 48, 52, and 56, ITT and Treatment-Naive Populations ITT Population	81.3 Percentage of participants Interval 76.8 to 85.9	78.0 Percentage of participants Interval 73.1 to 82.8	65.4 Percentage of participants Interval 59.9 to 70.8
Percentage of Participants With Absence of Diabetic Macular Edema in the Study Eye Averaged Over Weeks 48, 52, and 56, ITT and Treatment-Naive Populations Treatment-Naive Population	83.5 Percentage of participants Interval 78.4 to 88.5	80.4 Percentage of participants Interval 75.1 to 85.7	68.3 Percentage of participants Interval 62.1 to 74.4

SECONDARY outcome

Timeframe: Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, 56, 60, 64, 68, 72, 76, 80, 84, 88, 92, 96, and 100

Absence of diabetic macular edema was defined as achieving a central subfield thickness of \<325 microns in the study eye. Central subfield thickness was defined as the distance between the internal limiting membrane (ILM) and Bruch's membrane (BM) as assessed by a central reading center. The weighted estimates of the percentage of participants were based on the Cochran-Mantel Haenszel (CMH) weights stratified by baseline BCVA (≥64 vs. \<64 letters), prior IVT anti-VEGF therapy (yes vs. no), and region (U.S. and Canada vs. rest of the world; Asia and rest of the world regions were combined). Treatment policy strategy (i.e., all observed values used) and hypothetical strategy (i.e., all values censored after the occurrence of the intercurrent event) were applied to non-COVID-19 related and COVID-19 related intercurrent events, respectively. Missing data were not imputed. 95% confidence interval (CI) is a rounding of 95.04% CI.

Outcome measures

Outcome measures
Measure	A: Faricimab 6 mg Q8W n=315 Participants Participants randomized to Arm A received 6 milligrams (mg) faricimab intravitreal (IVT) injections once every 4 weeks (Q4W) to Week 20, followed by 6 mg faricimab IVT injections once every 8 weeks (Q8W) to Week 96, followed by the final study visit at Week 100.	B: Faricimab 6 mg PTI n=313 Participants Participants randomized to Arm B received 6 milligrams (mg) faricimab intravitreal (IVT) injections Q4W to at least Week 12, followed by a personalized treatment interval (PTI) dosing of 6 mg faricimab IVT injections up to once every 16 weeks (Q16W) through Week 96, followed by the final study visit at Week 100.	C: Aflibercept 2 mg Q8W n=312 Participants Participants randomized to Arm C received 2 milligrams (mg) aflibercept intravitreal (IVT) injections Q4W to Week 16, followed by 2 mg aflibercept IVT injections Q8W to Week 96, followed by the final study visit at Week 100.
Percentage of Participants With Absence of Diabetic Macular Edema in the Study Eye Over Time, ITT Population Week 4	36.1 Percentage of participants Interval 30.8 to 41.4	41.3 Percentage of participants Interval 35.9 to 46.8	35.0 Percentage of participants Interval 29.7 to 40.4
Percentage of Participants With Absence of Diabetic Macular Edema in the Study Eye Over Time, ITT Population Week 8	48.4 Percentage of participants Interval 42.9 to 54.0	52.7 Percentage of participants Interval 47.2 to 58.2	42.6 Percentage of participants Interval 37.1 to 48.2
Percentage of Participants With Absence of Diabetic Macular Edema in the Study Eye Over Time, ITT Population Week 12	60.9 Percentage of participants Interval 55.4 to 66.4	67.4 Percentage of participants Interval 62.1 to 72.6	49.6 Percentage of participants Interval 44.0 to 55.2
Percentage of Participants With Absence of Diabetic Macular Edema in the Study Eye Over Time, ITT Population Week 16	67.2 Percentage of participants Interval 61.8 to 72.5	72.0 Percentage of participants Interval 66.9 to 77.0	58.6 Percentage of participants Interval 53.1 to 64.1
Percentage of Participants With Absence of Diabetic Macular Edema in the Study Eye Over Time, ITT Population Week 20	71.1 Percentage of participants Interval 65.9 to 76.2	70.7 Percentage of participants Interval 65.6 to 75.8	58.9 Percentage of participants Interval 53.4 to 64.5
Percentage of Participants With Absence of Diabetic Macular Edema in the Study Eye Over Time, ITT Population Week 24	76.5 Percentage of participants Interval 71.7 to 81.4	81.3 Percentage of participants Interval 76.8 to 85.8	53.7 Percentage of participants Interval 48.1 to 59.4
Percentage of Participants With Absence of Diabetic Macular Edema in the Study Eye Over Time, ITT Population Week 28	71.4 Percentage of participants Interval 66.2 to 76.5	79.3 Percentage of participants Interval 74.6 to 84.0	62.5 Percentage of participants Interval 57.0 to 68.0
Percentage of Participants With Absence of Diabetic Macular Edema in the Study Eye Over Time, ITT Population Week 32	79.0 Percentage of participants Interval 74.2 to 83.8	72.1 Percentage of participants Interval 66.8 to 77.4	55.8 Percentage of participants Interval 50.1 to 61.5
Percentage of Participants With Absence of Diabetic Macular Edema in the Study Eye Over Time, ITT Population Week 36	70.9 Percentage of participants Interval 65.6 to 76.1	81.7 Percentage of participants Interval 77.1 to 86.3	63.1 Percentage of participants Interval 57.4 to 68.8
Percentage of Participants With Absence of Diabetic Macular Edema in the Study Eye Over Time, ITT Population Week 40	82.3 Percentage of participants Interval 77.9 to 86.7	80.8 Percentage of participants Interval 76.1 to 85.5	58.8 Percentage of participants Interval 53.0 to 64.7
Percentage of Participants With Absence of Diabetic Macular Edema in the Study Eye Over Time, ITT Population Week 44	74.7 Percentage of participants Interval 69.6 to 79.9	79.0 Percentage of participants Interval 74.3 to 83.8	67.6 Percentage of participants Interval 62.1 to 73.1
Percentage of Participants With Absence of Diabetic Macular Edema in the Study Eye Over Time, ITT Population Week 48	86.5 Percentage of participants Interval 82.5 to 90.5	81.5 Percentage of participants Interval 76.8 to 86.1	64.0 Percentage of participants Interval 58.3 to 69.7
Percentage of Participants With Absence of Diabetic Macular Edema in the Study Eye Over Time, ITT Population Week 52	77.4 Percentage of participants Interval 72.4 to 82.4	78.3 Percentage of participants Interval 73.4 to 83.1	71.1 Percentage of participants Interval 65.6 to 76.7
Percentage of Participants With Absence of Diabetic Macular Edema in the Study Eye Over Time, ITT Population Week 56	86.5 Percentage of participants Interval 82.4 to 90.7	81.3 Percentage of participants Interval 76.6 to 86.0	65.0 Percentage of participants Interval 59.2 to 70.8
Percentage of Participants With Absence of Diabetic Macular Edema in the Study Eye Over Time, ITT Population Week 60	78.8 Percentage of participants Interval 74.0 to 83.6	79.4 Percentage of participants Interval 74.6 to 84.3	72.3 Percentage of participants Interval 66.9 to 77.7
Percentage of Participants With Absence of Diabetic Macular Edema in the Study Eye Over Time, ITT Population Week 64	88.3 Percentage of participants Interval 84.4 to 92.2	80.0 Percentage of participants Interval 75.2 to 84.8	67.7 Percentage of participants Interval 62.1 to 73.3
Percentage of Participants With Absence of Diabetic Macular Edema in the Study Eye Over Time, ITT Population Week 68	83.5 Percentage of participants Interval 79.0 to 88.1	84.1 Percentage of participants Interval 79.7 to 88.5	74.8 Percentage of participants Interval 69.4 to 80.1
Percentage of Participants With Absence of Diabetic Macular Edema in the Study Eye Over Time, ITT Population Week 72	88.0 Percentage of participants Interval 84.0 to 92.0	85.2 Percentage of participants Interval 81.0 to 89.5	70.2 Percentage of participants Interval 64.5 to 75.9
Percentage of Participants With Absence of Diabetic Macular Edema in the Study Eye Over Time, ITT Population Week 76	85.6 Percentage of participants Interval 81.3 to 89.8	84.9 Percentage of participants Interval 80.5 to 89.2	76.0 Percentage of participants Interval 70.7 to 81.2
Percentage of Participants With Absence of Diabetic Macular Edema in the Study Eye Over Time, ITT Population Week 80	88.5 Percentage of participants Interval 84.5 to 92.4	81.9 Percentage of participants Interval 77.3 to 86.6	73.2 Percentage of participants Interval 67.7 to 78.7
Percentage of Participants With Absence of Diabetic Macular Edema in the Study Eye Over Time, ITT Population Week 84	85.1 Percentage of participants Interval 80.7 to 89.5	86.1 Percentage of participants Interval 82.0 to 90.3	74.9 Percentage of participants Interval 69.5 to 80.3
Percentage of Participants With Absence of Diabetic Macular Edema in the Study Eye Over Time, ITT Population Week 88	90.4 Percentage of participants Interval 86.8 to 94.0	83.2 Percentage of participants Interval 78.7 to 87.7	74.2 Percentage of participants Interval 68.7 to 79.6
Percentage of Participants With Absence of Diabetic Macular Edema in the Study Eye Over Time, ITT Population Week 92	86.5 Percentage of participants Interval 82.3 to 90.7	78.2 Percentage of participants Interval 73.2 to 83.3	78.2 Percentage of participants Interval 73.1 to 83.3
Percentage of Participants With Absence of Diabetic Macular Edema in the Study Eye Over Time, ITT Population Week 96	91.8 Percentage of participants Interval 88.4 to 95.3	83.7 Percentage of participants Interval 79.2 to 88.2	77.3 Percentage of participants Interval 72.1 to 82.4
Percentage of Participants With Absence of Diabetic Macular Edema in the Study Eye Over Time, ITT Population Week 100	89.5 Percentage of participants Interval 85.7 to 93.4	85.9 Percentage of participants Interval 81.7 to 90.1	81.0 Percentage of participants Interval 76.1 to 86.0

SECONDARY outcome

Timeframe: Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, 56, 60, 64, 68, 72, 76, 80, 84, 88, 92, 96, and 100

Retinal dryness was defined as achieving a central subfield thickness (ILM-BM) of \<280 microns. Central subfield thickness was defined as the distance between the internal limiting membrane (ILM) and Bruch's membrane (BM) as assessed by a central reading center. The weighted estimates of the percentage of participants was based on the Cochran-Mantel Haenszel (CMH) weights stratified by baseline BCVA (≥64 vs. \<64 letters), prior IVT anti-VEGF therapy (yes vs. no), and region (U.S. and Canada vs. rest of the world; Asia and rest of the world regions were combined). Treatment policy strategy (i.e., all observed values used) and hypothetical strategy (i.e., all values censored after the occurrence of the intercurrent event) were applied to non-COVID-19 related and COVID-19 related intercurrent events, respectively. Missing data were not imputed. 95% confidence interval (CI) is a rounding of 95.04% CI.

Outcome measures

Outcome measures
Measure	A: Faricimab 6 mg Q8W n=315 Participants Participants randomized to Arm A received 6 milligrams (mg) faricimab intravitreal (IVT) injections once every 4 weeks (Q4W) to Week 20, followed by 6 mg faricimab IVT injections once every 8 weeks (Q8W) to Week 96, followed by the final study visit at Week 100.	B: Faricimab 6 mg PTI n=313 Participants Participants randomized to Arm B received 6 milligrams (mg) faricimab intravitreal (IVT) injections Q4W to at least Week 12, followed by a personalized treatment interval (PTI) dosing of 6 mg faricimab IVT injections up to once every 16 weeks (Q16W) through Week 96, followed by the final study visit at Week 100.	C: Aflibercept 2 mg Q8W n=312 Participants Participants randomized to Arm C received 2 milligrams (mg) aflibercept intravitreal (IVT) injections Q4W to Week 16, followed by 2 mg aflibercept IVT injections Q8W to Week 96, followed by the final study visit at Week 100.
Percentage of Participants With Retinal Dryness in the Study Eye Over Time, ITT Population Week 4	15.4 Percentage of participants Interval 11.5 to 19.4	16.0 Percentage of participants Interval 12.0 to 19.9	12.6 Percentage of participants Interval 8.9 to 16.3
Percentage of Participants With Retinal Dryness in the Study Eye Over Time, ITT Population Week 8	24.2 Percentage of participants Interval 19.6 to 28.8	24.6 Percentage of participants Interval 19.9 to 29.3	16.2 Percentage of participants Interval 12.1 to 20.3
Percentage of Participants With Retinal Dryness in the Study Eye Over Time, ITT Population Week 12	32.4 Percentage of participants Interval 27.3 to 37.5	34.1 Percentage of participants Interval 28.9 to 39.4	22.1 Percentage of participants Interval 17.4 to 26.7
Percentage of Participants With Retinal Dryness in the Study Eye Over Time, ITT Population Week 16	38.4 Percentage of participants Interval 33.0 to 43.9	42.5 Percentage of participants Interval 36.9 to 48.0	23.2 Percentage of participants Interval 18.5 to 27.9
Percentage of Participants With Retinal Dryness in the Study Eye Over Time, ITT Population Week 20	45.9 Percentage of participants Interval 40.3 to 51.5	40.6 Percentage of participants Interval 35.0 to 46.1	29.7 Percentage of participants Interval 24.5 to 34.8
Percentage of Participants With Retinal Dryness in the Study Eye Over Time, ITT Population Week 24	53.0 Percentage of participants Interval 47.3 to 58.7	48.1 Percentage of participants Interval 42.4 to 53.8	26.6 Percentage of participants Interval 21.6 to 31.6
Percentage of Participants With Retinal Dryness in the Study Eye Over Time, ITT Population Week 28	45.9 Percentage of participants Interval 40.1 to 51.7	50.2 Percentage of participants Interval 44.4 to 55.9	34.3 Percentage of participants Interval 28.8 to 39.8
Percentage of Participants With Retinal Dryness in the Study Eye Over Time, ITT Population Week 32	55.0 Percentage of participants Interval 49.1 to 60.8	43.2 Percentage of participants Interval 37.3 to 49.0	30.6 Percentage of participants Interval 25.1 to 36.1
Percentage of Participants With Retinal Dryness in the Study Eye Over Time, ITT Population Week 36	48.5 Percentage of participants Interval 42.5 to 54.5	54.3 Percentage of participants Interval 48.4 to 60.3	39.2 Percentage of participants Interval 33.4 to 45.1
Percentage of Participants With Retinal Dryness in the Study Eye Over Time, ITT Population Week 40	57.5 Percentage of participants Interval 51.8 to 63.2	51.3 Percentage of participants Interval 45.3 to 57.3	32.2 Percentage of participants Interval 26.7 to 37.7
Percentage of Participants With Retinal Dryness in the Study Eye Over Time, ITT Population Week 44	51.5 Percentage of participants Interval 45.7 to 57.4	51.9 Percentage of participants Interval 46.1 to 57.8	37.1 Percentage of participants Interval 31.4 to 42.8
Percentage of Participants With Retinal Dryness in the Study Eye Over Time, ITT Population Week 48	63.2 Percentage of participants Interval 57.4 to 69.0	50.1 Percentage of participants Interval 44.2 to 56.0	36.2 Percentage of participants Interval 30.4 to 42.0
Percentage of Participants With Retinal Dryness in the Study Eye Over Time, ITT Population Week 52	57.8 Percentage of participants Interval 51.9 to 63.7	54.7 Percentage of participants Interval 48.7 to 60.6	42.3 Percentage of participants Interval 36.2 to 48.4
Percentage of Participants With Retinal Dryness in the Study Eye Over Time, ITT Population Week 56	66.3 Percentage of participants Interval 60.6 to 72.0	56.9 Percentage of participants Interval 51.0 to 62.9	41.2 Percentage of participants Interval 35.1 to 47.2
Percentage of Participants With Retinal Dryness in the Study Eye Over Time, ITT Population Week 60	60.2 Percentage of participants Interval 54.4 to 66.0	54.0 Percentage of participants Interval 48.0 to 60.0	47.7 Percentage of participants Interval 41.6 to 53.7
Percentage of Participants With Retinal Dryness in the Study Eye Over Time, ITT Population Week 64	68.5 Percentage of participants Interval 62.8 to 74.1	55.4 Percentage of participants Interval 49.4 to 61.3	47.4 Percentage of participants Interval 41.3 to 53.4
Percentage of Participants With Retinal Dryness in the Study Eye Over Time, ITT Population Week 68	61.3 Percentage of participants Interval 55.3 to 67.3	57.7 Percentage of participants Interval 51.7 to 63.8	52.3 Percentage of participants Interval 46.1 to 58.5
Percentage of Participants With Retinal Dryness in the Study Eye Over Time, ITT Population Week 72	65.8 Percentage of participants Interval 60.1 to 71.5	58.5 Percentage of participants Interval 52.6 to 64.3	47.7 Percentage of participants Interval 41.4 to 53.9
Percentage of Participants With Retinal Dryness in the Study Eye Over Time, ITT Population Week 76	65.9 Percentage of participants Interval 60.1 to 71.8	54.8 Percentage of participants Interval 48.6 to 60.9	53.9 Percentage of participants Interval 47.7 to 60.1
Percentage of Participants With Retinal Dryness in the Study Eye Over Time, ITT Population Week 80	70.1 Percentage of participants Interval 64.5 to 75.8	54.7 Percentage of participants Interval 48.7 to 60.6	51.1 Percentage of participants Interval 44.8 to 57.3
Percentage of Participants With Retinal Dryness in the Study Eye Over Time, ITT Population Week 84	67.1 Percentage of participants Interval 61.3 to 72.9	61.2 Percentage of participants Interval 55.5 to 67.0	56.0 Percentage of participants Interval 49.9 to 62.2
Percentage of Participants With Retinal Dryness in the Study Eye Over Time, ITT Population Week 88	72.2 Percentage of participants Interval 66.7 to 77.7	58.0 Percentage of participants Interval 52.1 to 64.0	54.2 Percentage of participants Interval 48.0 to 60.5
Percentage of Participants With Retinal Dryness in the Study Eye Over Time, ITT Population Week 92	66.2 Percentage of participants Interval 60.5 to 72.0	58.0 Percentage of participants Interval 52.2 to 63.8	57.9 Percentage of participants Interval 51.7 to 64.0
Percentage of Participants With Retinal Dryness in the Study Eye Over Time, ITT Population Week 96	72.7 Percentage of participants Interval 67.2 to 78.2	61.4 Percentage of participants Interval 55.6 to 67.2	58.0 Percentage of participants Interval 51.8 to 64.2
Percentage of Participants With Retinal Dryness in the Study Eye Over Time, ITT Population Week 100	71.4 Percentage of participants Interval 65.9 to 76.8	60.5 Percentage of participants Interval 54.5 to 66.4	60.7 Percentage of participants Interval 54.5 to 66.8

SECONDARY outcome

Timeframe: Baseline, Weeks 16, 48, 52, 56, 92, 96, and 100

Intraretinal fluid was measured using optical coherence tomography (OCT) in the central subfield (center 1 mm). The weighted estimates of the percentage of participants were based on the Cochran-Mantel Haenszel (CMH) weights stratified by baseline BCVA (≥64 vs. \<64 letters), prior IVT anti-VEGF therapy (yes vs. no), and region (U.S. and Canada vs. rest of the world); Asia and rest of the world regions were combined due to a small number of enrolled participants. Treatment policy strategy (i.e., all observed values used) and hypothetical strategy (i.e., all values censored after the occurrence of the intercurrent event) were applied to non-COVID-19 related and COVID-19 related intercurrent events, respectively. Missing data were not imputed. 95% confidence interval (CI) is a rounding of 95.04% CI.

Outcome measures

Outcome measures
Measure	A: Faricimab 6 mg Q8W n=315 Participants Participants randomized to Arm A received 6 milligrams (mg) faricimab intravitreal (IVT) injections once every 4 weeks (Q4W) to Week 20, followed by 6 mg faricimab IVT injections once every 8 weeks (Q8W) to Week 96, followed by the final study visit at Week 100.	B: Faricimab 6 mg PTI n=313 Participants Participants randomized to Arm B received 6 milligrams (mg) faricimab intravitreal (IVT) injections Q4W to at least Week 12, followed by a personalized treatment interval (PTI) dosing of 6 mg faricimab IVT injections up to once every 16 weeks (Q16W) through Week 96, followed by the final study visit at Week 100.	C: Aflibercept 2 mg Q8W n=312 Participants Participants randomized to Arm C received 2 milligrams (mg) aflibercept intravitreal (IVT) injections Q4W to Week 16, followed by 2 mg aflibercept IVT injections Q8W to Week 96, followed by the final study visit at Week 100.
Percentage of Participants With Absence of Intraretinal Fluid in the Study Eye Over Time, ITT Population Week 16	16.3 Percentage of participants Interval 12.0 to 20.5	21.9 Percentage of participants Interval 17.1 to 26.6	13.4 Percentage of participants Interval 9.6 to 17.3
Percentage of Participants With Absence of Intraretinal Fluid in the Study Eye Over Time, ITT Population Week 48	45.6 Percentage of participants Interval 39.7 to 51.6	33.2 Percentage of participants Interval 27.5 to 38.9	21.9 Percentage of participants Interval 17.0 to 26.9
Percentage of Participants With Absence of Intraretinal Fluid in the Study Eye Over Time, ITT Population Week 52	42.1 Percentage of participants Interval 36.3 to 47.9	38.8 Percentage of participants Interval 32.9 to 44.7	25.5 Percentage of participants Interval 20.2 to 30.8
Percentage of Participants With Absence of Intraretinal Fluid in the Study Eye Over Time, ITT Population Week 56	49.3 Percentage of participants Interval 43.3 to 55.3	42.7 Percentage of participants Interval 36.7 to 48.7	23.7 Percentage of participants Interval 18.5 to 28.9
Percentage of Participants With Absence of Intraretinal Fluid in the Study Eye Over Time, ITT Population Week 92	58.5 Percentage of participants Interval 52.3 to 64.7	43.2 Percentage of participants Interval 37.1 to 49.3	33.2 Percentage of participants Interval 27.4 to 39.1
Percentage of Participants With Absence of Intraretinal Fluid in the Study Eye Over Time, ITT Population Week 96	63.1 Percentage of participants Interval 57.0 to 69.2	47.6 Percentage of participants Interval 41.5 to 53.7	34.6 Percentage of participants Interval 28.7 to 40.6
Percentage of Participants With Absence of Intraretinal Fluid in the Study Eye Over Time, ITT Population Week 100	61.4 Percentage of participants Interval 55.2 to 67.5	44.5 Percentage of participants Interval 38.4 to 50.7	37.6 Percentage of participants Interval 31.5 to 43.6

SECONDARY outcome

Timeframe: Baseline, Weeks 16, 48, 52, 56, 92, 96, and 100

Subretinal fluid was measured using optical coherence tomography (OCT) in the central subfield (center 1 mm). The weighted estimates of the percentage of participants were based on the Cochran-Mantel Haenszel (CMH) weights stratified by baseline BCVA (≥64 vs. \<64 letters), prior IVT anti-VEGF therapy (yes vs. no), and region (U.S. and Canada vs. rest of the world); Asia and rest of the world regions were combined due to a small number of enrolled participants. Treatment policy strategy (i.e., all observed values used) and hypothetical strategy (i.e., all values censored after the occurrence of the intercurrent event) were applied to non-COVID-19 related and COVID-19 related intercurrent events, respectively. Missing data were not imputed. 95% confidence interval (CI) is a rounding of 95.04% CI.

Outcome measures

Outcome measures
Measure	A: Faricimab 6 mg Q8W n=315 Participants Participants randomized to Arm A received 6 milligrams (mg) faricimab intravitreal (IVT) injections once every 4 weeks (Q4W) to Week 20, followed by 6 mg faricimab IVT injections once every 8 weeks (Q8W) to Week 96, followed by the final study visit at Week 100.	B: Faricimab 6 mg PTI n=313 Participants Participants randomized to Arm B received 6 milligrams (mg) faricimab intravitreal (IVT) injections Q4W to at least Week 12, followed by a personalized treatment interval (PTI) dosing of 6 mg faricimab IVT injections up to once every 16 weeks (Q16W) through Week 96, followed by the final study visit at Week 100.	C: Aflibercept 2 mg Q8W n=312 Participants Participants randomized to Arm C received 2 milligrams (mg) aflibercept intravitreal (IVT) injections Q4W to Week 16, followed by 2 mg aflibercept IVT injections Q8W to Week 96, followed by the final study visit at Week 100.
Percentage of Participants With Absence of Subretinal Fluid in the Study Eye Over Time, ITT Population Week 16	95.3 Percentage of participants Interval 92.9 to 97.7	94.5 Percentage of participants Interval 92.0 to 97.1	95.9 Percentage of participants Interval 93.7 to 98.2
Percentage of Participants With Absence of Subretinal Fluid in the Study Eye Over Time, ITT Population Week 48	97.0 Percentage of participants Interval 95.0 to 99.0	95.5 Percentage of participants Interval 93.1 to 97.9	96.2 Percentage of participants Interval 93.8 to 98.5
Percentage of Participants With Absence of Subretinal Fluid in the Study Eye Over Time, ITT Population Week 52	95.8 Percentage of participants Interval 93.3 to 98.2	95.4 Percentage of participants Interval 92.9 to 97.9	98.0 Percentage of participants Interval 96.2 to 99.7
Percentage of Participants With Absence of Subretinal Fluid in the Study Eye Over Time, ITT Population Week 56	97.0 Percentage of participants Interval 95.0 to 99.0	97.0 Percentage of participants Interval 95.0 to 99.0	97.3 Percentage of participants Interval 95.3 to 99.3
Percentage of Participants With Absence of Subretinal Fluid in the Study Eye Over Time, ITT Population Week 92	94.8 Percentage of participants Interval 92.1 to 97.6	94.5 Percentage of participants Interval 91.7 to 97.3	96.7 Percentage of participants Interval 94.5 to 99.0
Percentage of Participants With Absence of Subretinal Fluid in the Study Eye Over Time, ITT Population Week 96	97.0 Percentage of participants Interval 94.8 to 99.1	94.1 Percentage of participants Interval 91.3 to 97.0	96.7 Percentage of participants Interval 94.5 to 98.9
Percentage of Participants With Absence of Subretinal Fluid in the Study Eye Over Time, ITT Population Week 100	94.3 Percentage of participants Interval 91.4 to 97.2	97.3 Percentage of participants Interval 95.4 to 99.2	97.1 Percentage of participants Interval 95.0 to 99.2

SECONDARY outcome

Timeframe: Baseline, Weeks 16, 48, 52, 56, 92, 96, and 100

Intraretinal fluid and subretinal fluid were measured using optical coherence tomography (OCT) in the central subfield (center 1 mm). The weighted estimates of the percentage of participants were based on the Cochran-Mantel Haenszel (CMH) weights stratified by baseline BCVA (≥64 vs. \<64 letters), prior IVT anti-VEGF therapy (yes vs. no), and region (U.S. and Canada vs. rest of the world); Asia and rest of the world regions were combined due to a small number of enrolled participants. Treatment policy strategy (i.e., all observed values used) and hypothetical strategy (i.e., all values censored after the occurrence of the intercurrent event) were applied to non-COVID-19 related and COVID-19 related intercurrent events, respectively. Missing data were not imputed. 95% confidence interval (CI) is a rounding of 95.04% CI.

Outcome measures

Outcome measures
Measure	A: Faricimab 6 mg Q8W n=315 Participants Participants randomized to Arm A received 6 milligrams (mg) faricimab intravitreal (IVT) injections once every 4 weeks (Q4W) to Week 20, followed by 6 mg faricimab IVT injections once every 8 weeks (Q8W) to Week 96, followed by the final study visit at Week 100.	B: Faricimab 6 mg PTI n=313 Participants Participants randomized to Arm B received 6 milligrams (mg) faricimab intravitreal (IVT) injections Q4W to at least Week 12, followed by a personalized treatment interval (PTI) dosing of 6 mg faricimab IVT injections up to once every 16 weeks (Q16W) through Week 96, followed by the final study visit at Week 100.	C: Aflibercept 2 mg Q8W n=312 Participants Participants randomized to Arm C received 2 milligrams (mg) aflibercept intravitreal (IVT) injections Q4W to Week 16, followed by 2 mg aflibercept IVT injections Q8W to Week 96, followed by the final study visit at Week 100.
Percentage of Participants With Absence of Intraretinal Fluid and Subretinal Fluid in the Study Eye Over Time, ITT Population Week 16	15.9 Percentage of participants Interval 11.7 to 20.1	21.9 Percentage of participants Interval 17.1 to 26.6	13.1 Percentage of participants Interval 9.3 to 16.9
Percentage of Participants With Absence of Intraretinal Fluid and Subretinal Fluid in the Study Eye Over Time, ITT Population Week 48	45.2 Percentage of participants Interval 39.3 to 51.2	32.4 Percentage of participants Interval 26.8 to 38.1	21.9 Percentage of participants Interval 17.0 to 26.9
Percentage of Participants With Absence of Intraretinal Fluid and Subretinal Fluid in the Study Eye Over Time, ITT Population Week 52	42.1 Percentage of participants Interval 36.3 to 47.9	38.0 Percentage of participants Interval 32.2 to 43.8	25.5 Percentage of participants Interval 20.2 to 30.8
Percentage of Participants With Absence of Intraretinal Fluid and Subretinal Fluid in the Study Eye Over Time, ITT Population Week 56	47.0 Percentage of participants Interval 41.0 to 53.0	42.4 Percentage of participants Interval 36.4 to 48.3	23.7 Percentage of participants Interval 18.5 to 28.9
Percentage of Participants With Absence of Intraretinal Fluid and Subretinal Fluid in the Study Eye Over Time, ITT Population Week 92	57.2 Percentage of participants Interval 51.0 to 63.4	41.3 Percentage of participants Interval 35.2 to 47.3	32.0 Percentage of participants Interval 26.3 to 37.8
Percentage of Participants With Absence of Intraretinal Fluid and Subretinal Fluid in the Study Eye Over Time, ITT Population Week 96	62.4 Percentage of participants Interval 56.2 to 68.5	46.0 Percentage of participants Interval 39.8 to 52.1	34.2 Percentage of participants Interval 28.3 to 40.1
Percentage of Participants With Absence of Intraretinal Fluid and Subretinal Fluid in the Study Eye Over Time, ITT Population Week 100	59.3 Percentage of participants Interval 53.0 to 65.5	43.8 Percentage of participants Interval 37.6 to 49.9	37.4 Percentage of participants Interval 31.4 to 43.5

SECONDARY outcome

Timeframe: Baseline, Weeks 24, 52, and 100

Population: ITT Population: all participants who were randomized in the study, grouped according to the treatment assigned at randomization.

The NEI VFQ-25 captures a patient's perception of vision-related functioning and quality of life. The core measure includes 25 items that comprise 11 vision-related subscales and one item on general health. The composite score ranges from 0 to 100, with higher scores, or a positive change from baseline, indicating better vision-related functioning. For the Mixed Model for Repeated Measures (MMRM) analysis, the model adjusted for treatment arm, visit, visit-by-treatment arm interaction, baseline NEI VFQ-25 Composite Score (continuous), baseline BCVA (\<64 vs. ≥64 letters), prior intravitreal anti-VEGF therapy (yes vs. no), and region of enrollment. An unstructured covariance structure was used. Treatment policy strategy and hypothetical strategy were applied to non-COVID-19 related and COVID-19 related intercurrent events, respectively. Missing data were implicitly imputed by MMRM. 95% CI is a rounding of 95.04% CI.

Outcome measures

Outcome measures
Measure	A: Faricimab 6 mg Q8W n=315 Participants Participants randomized to Arm A received 6 milligrams (mg) faricimab intravitreal (IVT) injections once every 4 weeks (Q4W) to Week 20, followed by 6 mg faricimab IVT injections once every 8 weeks (Q8W) to Week 96, followed by the final study visit at Week 100.	B: Faricimab 6 mg PTI n=313 Participants Participants randomized to Arm B received 6 milligrams (mg) faricimab intravitreal (IVT) injections Q4W to at least Week 12, followed by a personalized treatment interval (PTI) dosing of 6 mg faricimab IVT injections up to once every 16 weeks (Q16W) through Week 96, followed by the final study visit at Week 100.	C: Aflibercept 2 mg Q8W n=312 Participants Participants randomized to Arm C received 2 milligrams (mg) aflibercept intravitreal (IVT) injections Q4W to Week 16, followed by 2 mg aflibercept IVT injections Q8W to Week 96, followed by the final study visit at Week 100.
Change From Baseline in the National Eye Institute Visual Functioning Questionnaire-25 (NEI VFQ-25) Composite Score Over Time, ITT Population Week 24	6.0 score on a scale Interval 4.8 to 7.2	6.9 score on a scale Interval 5.7 to 8.1	6.0 score on a scale Interval 4.8 to 7.2
Change From Baseline in the National Eye Institute Visual Functioning Questionnaire-25 (NEI VFQ-25) Composite Score Over Time, ITT Population Week 52	7.3 score on a scale Interval 5.9 to 8.6	7.9 score on a scale Interval 6.6 to 9.3	7.5 score on a scale Interval 6.1 to 8.9
Change From Baseline in the National Eye Institute Visual Functioning Questionnaire-25 (NEI VFQ-25) Composite Score Over Time, ITT Population Week 100	8.0 score on a scale Interval 6.6 to 9.4	7.4 score on a scale Interval 6.0 to 8.8	7.6 score on a scale Interval 6.1 to 9.0

SECONDARY outcome

Timeframe: From first dose of study drug through end of study (up to 2 years)

Population: The safety-evaluable population comprised all participants who received at least one injection of active study drug (faricimab or aflibercept) in the study eye.

This analysis of adverse events (AEs) includes both ocular and non-ocular (systemic) AEs. Investigators sought information on AEs at each contact with the participants. All AEs were recorded and the investigator made an assessment of seriousness, severity, and causality of each AE. AEs of special interest included the following: Cases of potential drug-induced liver injury that include an elevated ALT or AST in combination with either an elevated bilirubin or clinical jaundice, as defined by Hy's Law; Suspected transmission of an infectious agent by the study drug; Sight-threatening AEs that cause a drop in visual acuity (VA) score ≥30 letters lasting more than 1 hour, require surgical or medical intervention to prevent permanent loss of sight, or are associated with severe intraocular inflammation.

Outcome measures

Outcome measures
Measure	A: Faricimab 6 mg Q8W n=313 Participants Participants randomized to Arm A received 6 milligrams (mg) faricimab intravitreal (IVT) injections once every 4 weeks (Q4W) to Week 20, followed by 6 mg faricimab IVT injections once every 8 weeks (Q8W) to Week 96, followed by the final study visit at Week 100.	B: Faricimab 6 mg PTI n=313 Participants Participants randomized to Arm B received 6 milligrams (mg) faricimab intravitreal (IVT) injections Q4W to at least Week 12, followed by a personalized treatment interval (PTI) dosing of 6 mg faricimab IVT injections up to once every 16 weeks (Q16W) through Week 96, followed by the final study visit at Week 100.	C: Aflibercept 2 mg Q8W n=311 Participants Participants randomized to Arm C received 2 milligrams (mg) aflibercept intravitreal (IVT) injections Q4W to Week 16, followed by 2 mg aflibercept IVT injections Q8W to Week 96, followed by the final study visit at Week 100.
Percentage of Participants With at Least One Adverse Event Adverse Event (AE)	92.7 Percentage of participants	91.4 Percentage of participants	89.1 Percentage of participants
Percentage of Participants With at Least One Adverse Event Serious AE (SAE)	35.5 Percentage of participants	37.4 Percentage of participants	29.9 Percentage of participants
Percentage of Participants With at Least One Adverse Event AE Leading to Withdrawal from Study Treatment	2.6 Percentage of participants	2.9 Percentage of participants	1.6 Percentage of participants
Percentage of Participants With at Least One Adverse Event AE of Special Interest (AESI)	6.1 Percentage of participants	7.0 Percentage of participants	4.8 Percentage of participants

SECONDARY outcome

Timeframe: From first dose of study drug through end of study (up to 2 years)

Population: The safety-evaluable population comprised all participants who received at least one injection of active study drug (faricimab or aflibercept) in the study eye.

This analysis of adverse events (AEs) only includes ocular AEs, which are categorized as having occurred either in the study eye or the fellow eye. Investigators sought information on AEs at each contact with the participants. All AEs were recorded and the investigator made an assessment of seriousness, severity, and causality of each AE. Ocular AEs of special interest included the following: Suspected transmission of an infectious agent by the study drug; Sight-threatening AEs that cause a drop in visual acuity (VA) score ≥30 letters lasting more than 1 hour, require surgical or medical intervention to prevent permanent loss of sight, or are associated with severe intraocular inflammation.

Outcome measures

Outcome measures
Measure	A: Faricimab 6 mg Q8W n=313 Participants Participants randomized to Arm A received 6 milligrams (mg) faricimab intravitreal (IVT) injections once every 4 weeks (Q4W) to Week 20, followed by 6 mg faricimab IVT injections once every 8 weeks (Q8W) to Week 96, followed by the final study visit at Week 100.	B: Faricimab 6 mg PTI n=313 Participants Participants randomized to Arm B received 6 milligrams (mg) faricimab intravitreal (IVT) injections Q4W to at least Week 12, followed by a personalized treatment interval (PTI) dosing of 6 mg faricimab IVT injections up to once every 16 weeks (Q16W) through Week 96, followed by the final study visit at Week 100.	C: Aflibercept 2 mg Q8W n=311 Participants Participants randomized to Arm C received 2 milligrams (mg) aflibercept intravitreal (IVT) injections Q4W to Week 16, followed by 2 mg aflibercept IVT injections Q8W to Week 96, followed by the final study visit at Week 100.
Percentage of Participants With at Least One Ocular Adverse Event in the Study Eye or the Fellow Eye Fellow Eye: AESI	2.9 Percentage of participants	2.9 Percentage of participants	2.3 Percentage of participants
Percentage of Participants With at Least One Ocular Adverse Event in the Study Eye or the Fellow Eye Fellow Eye: AESI, Drop in VA Score ≥30 Letters	2.2 Percentage of participants	1.9 Percentage of participants	1.3 Percentage of participants
Percentage of Participants With at Least One Ocular Adverse Event in the Study Eye or the Fellow Eye Fellow Eye: AESI, Associated with Severe IOI	0.0 Percentage of participants	0.3 Percentage of participants	0.0 Percentage of participants
Percentage of Participants With at Least One Ocular Adverse Event in the Study Eye or the Fellow Eye Fellow Eye: AESI, Intervention Req. to Prevent Permanent Vision Loss	1.0 Percentage of participants	1.3 Percentage of participants	1.0 Percentage of participants
Percentage of Participants With at Least One Ocular Adverse Event in the Study Eye or the Fellow Eye Study Eye: Adverse Event (AE)	47.0 Percentage of participants	46.6 Percentage of participants	46.3 Percentage of participants
Percentage of Participants With at Least One Ocular Adverse Event in the Study Eye or the Fellow Eye Study Eye: Serious AE (SAE)	3.8 Percentage of participants	4.5 Percentage of participants	2.3 Percentage of participants
Percentage of Participants With at Least One Ocular Adverse Event in the Study Eye or the Fellow Eye Study Eye: AE Leading to Withdrawal from Treatment	1.3 Percentage of participants	1.9 Percentage of participants	0.3 Percentage of participants
Percentage of Participants With at Least One Ocular Adverse Event in the Study Eye or the Fellow Eye Study Eye: Treatment-related AE	3.2 Percentage of participants	2.2 Percentage of participants	1.9 Percentage of participants
Percentage of Participants With at Least One Ocular Adverse Event in the Study Eye or the Fellow Eye Study Eye: Treatment-related SAE	0.0 Percentage of participants	1.3 Percentage of participants	0.0 Percentage of participants
Percentage of Participants With at Least One Ocular Adverse Event in the Study Eye or the Fellow Eye Study Eye: AE of Special Interest (AESI)	3.5 Percentage of participants	4.2 Percentage of participants	2.6 Percentage of participants
Percentage of Participants With at Least One Ocular Adverse Event in the Study Eye or the Fellow Eye Study Eye: AESI, Drop in VA Score ≥30 Letters	2.6 Percentage of participants	2.2 Percentage of participants	2.3 Percentage of participants
Percentage of Participants With at Least One Ocular Adverse Event in the Study Eye or the Fellow Eye Study Eye: AESI, Associated with Severe IOI	0.6 Percentage of participants	1.6 Percentage of participants	0.0 Percentage of participants
Percentage of Participants With at Least One Ocular Adverse Event in the Study Eye or the Fellow Eye Study Eye: AESI, Intervention Req. to Prevent Permanent Vision Loss	1.0 Percentage of participants	1.3 Percentage of participants	0.3 Percentage of participants
Percentage of Participants With at Least One Ocular Adverse Event in the Study Eye or the Fellow Eye Fellow Eye: AE	40.3 Percentage of participants	42.2 Percentage of participants	46.3 Percentage of participants
Percentage of Participants With at Least One Ocular Adverse Event in the Study Eye or the Fellow Eye Fellow Eye: SAE	2.9 Percentage of participants	3.5 Percentage of participants	2.3 Percentage of participants

SECONDARY outcome

Timeframe: From first dose of study drug through end of study (up to 2 years)

Population: The safety-evaluable population comprised all participants who received at least one injection of active study drug (faricimab or aflibercept) in the study eye.

This analysis of adverse events (AEs) only includes non-ocular (systemic) AEs. Investigators sought information on adverse events (AEs) at each contact with the participants. All AEs were recorded and the investigator made an assessment of seriousness, severity, and causality of each AE. The non-ocular AE of special interest was: Cases of potential drug-induced liver injury that include an elevated ALT or AST in combination with either an elevated bilirubin or clinical jaundice, as defined by Hy's Law.

Outcome measures

Outcome measures
Measure	A: Faricimab 6 mg Q8W n=313 Participants Participants randomized to Arm A received 6 milligrams (mg) faricimab intravitreal (IVT) injections once every 4 weeks (Q4W) to Week 20, followed by 6 mg faricimab IVT injections once every 8 weeks (Q8W) to Week 96, followed by the final study visit at Week 100.	B: Faricimab 6 mg PTI n=313 Participants Participants randomized to Arm B received 6 milligrams (mg) faricimab intravitreal (IVT) injections Q4W to at least Week 12, followed by a personalized treatment interval (PTI) dosing of 6 mg faricimab IVT injections up to once every 16 weeks (Q16W) through Week 96, followed by the final study visit at Week 100.	C: Aflibercept 2 mg Q8W n=311 Participants Participants randomized to Arm C received 2 milligrams (mg) aflibercept intravitreal (IVT) injections Q4W to Week 16, followed by 2 mg aflibercept IVT injections Q8W to Week 96, followed by the final study visit at Week 100.
Percentage of Participants With at Least One Non-Ocular Adverse Event AE of Special Interest (AESI)	0.0 Percentage of participants	0.0 Percentage of participants	0.3 Percentage of participants
Percentage of Participants With at Least One Non-Ocular Adverse Event AESI, Elevated ALT or AST with Either Elevated Bilirubin or Clinical Jaundice	0.0 Percentage of participants	0.0 Percentage of participants	0.3 Percentage of participants
Percentage of Participants With at Least One Non-Ocular Adverse Event Adverse Event (AE)	76.7 Percentage of participants	80.2 Percentage of participants	77.8 Percentage of participants
Percentage of Participants With at Least One Non-Ocular Adverse Event Serious AE (SAE)	31.6 Percentage of participants	31.0 Percentage of participants	27.0 Percentage of participants
Percentage of Participants With at Least One Non-Ocular Adverse Event AE Leading to Withdrawal from Study Treatment	1.3 Percentage of participants	1.0 Percentage of participants	1.3 Percentage of participants

SECONDARY outcome

Timeframe: Pre-dose on Day 1 (Baseline); Weeks 4, 28, 52, 76, and 100

Population: This analysis only included participants in Arms A and B who received treatment with faricimab and with at least one plasma sample, provided sufficient dosing information (dose and dosing time) was available. The number of participants analyzed at a given timepoint includes those with an available plasma sample and dosing information at that timepoint.

Faricimab concentration in plasma was determined using a validated immunoassay method.

Outcome measures

Outcome measures
Measure	A: Faricimab 6 mg Q8W n=313 Participants Participants randomized to Arm A received 6 milligrams (mg) faricimab intravitreal (IVT) injections once every 4 weeks (Q4W) to Week 20, followed by 6 mg faricimab IVT injections once every 8 weeks (Q8W) to Week 96, followed by the final study visit at Week 100.	B: Faricimab 6 mg PTI n=311 Participants Participants randomized to Arm B received 6 milligrams (mg) faricimab intravitreal (IVT) injections Q4W to at least Week 12, followed by a personalized treatment interval (PTI) dosing of 6 mg faricimab IVT injections up to once every 16 weeks (Q16W) through Week 96, followed by the final study visit at Week 100.	C: Aflibercept 2 mg Q8W Participants randomized to Arm C received 2 milligrams (mg) aflibercept intravitreal (IVT) injections Q4W to Week 16, followed by 2 mg aflibercept IVT injections Q8W to Week 96, followed by the final study visit at Week 100.
Plasma Concentration of Faricimab Over Time Baseline	0.0000 micrograms per millilitre (μg/mL) Standard Deviation 0.0001	0.0000 micrograms per millilitre (μg/mL) Standard Deviation 0.0001	—
Plasma Concentration of Faricimab Over Time Week 4	0.0211 micrograms per millilitre (μg/mL) Standard Deviation 0.0337	0.0181 micrograms per millilitre (μg/mL) Standard Deviation 0.0139	—
Plasma Concentration of Faricimab Over Time Week 28	0.0033 micrograms per millilitre (μg/mL) Standard Deviation 0.0053	0.0089 micrograms per millilitre (μg/mL) Standard Deviation 0.0145	—
Plasma Concentration of Faricimab Over Time Week 52	0.0052 micrograms per millilitre (μg/mL) Standard Deviation 0.0104	0.0100 micrograms per millilitre (μg/mL) Standard Deviation 0.0132	—
Plasma Concentration of Faricimab Over Time Week 76	0.0048 micrograms per millilitre (μg/mL) Standard Deviation 0.0085	0.0068 micrograms per millilitre (μg/mL) Standard Deviation 0.0255	—
Plasma Concentration of Faricimab Over Time Week 100	0.0052 micrograms per millilitre (μg/mL) Standard Deviation 0.0087	0.0077 micrograms per millilitre (μg/mL) Standard Deviation 0.0126	—

SECONDARY outcome

Timeframe: Baseline, Weeks 4, 28, 52, 76, and 100

Population: The analysis population consisted of all participants receiving faricimab with at least one determinant post-baseline ADA assessment.

Anti-drug antibodies (ADAs) against fariciamb were detected in plasma using a validated bridging enzyme-linked immunosorbent assay (ELISA). The percentage of participants with treatment-emergent ADA-positive samples includes post-baseline evaluable participants with at least one treatment-induced (defined as having an ADA-negative sample or missing sample at baseline and any positive post-baseline sample) or treatment-boosted (defined as having an ADA-positive sample at baseline and any positive post-baseline sample with a titer that is equal to or greater than 4-fold baseline titer) ADA-positive sample during the study treatment period.

Outcome measures

Outcome measures
Measure	A: Faricimab 6 mg Q8W n=310 Participants Participants randomized to Arm A received 6 milligrams (mg) faricimab intravitreal (IVT) injections once every 4 weeks (Q4W) to Week 20, followed by 6 mg faricimab IVT injections once every 8 weeks (Q8W) to Week 96, followed by the final study visit at Week 100.	B: Faricimab 6 mg PTI n=311 Participants Participants randomized to Arm B received 6 milligrams (mg) faricimab intravitreal (IVT) injections Q4W to at least Week 12, followed by a personalized treatment interval (PTI) dosing of 6 mg faricimab IVT injections up to once every 16 weeks (Q16W) through Week 96, followed by the final study visit at Week 100.	C: Aflibercept 2 mg Q8W Participants randomized to Arm C received 2 milligrams (mg) aflibercept intravitreal (IVT) injections Q4W to Week 16, followed by 2 mg aflibercept IVT injections Q8W to Week 96, followed by the final study visit at Week 100.
Percentage of Participants Who Test Positive for Treatment-Emergent Anti-Drug Antibodies Against Faricimab During the Study Total Treatment-Emergent ADA-Positive	12.6 Percentage of participants	10.6 Percentage of participants	—
Percentage of Participants Who Test Positive for Treatment-Emergent Anti-Drug Antibodies Against Faricimab During the Study Treatment-Induced ADA-Positive	12.6 Percentage of participants	10.3 Percentage of participants	—
Percentage of Participants Who Test Positive for Treatment-Emergent Anti-Drug Antibodies Against Faricimab During the Study Treatment-Boosted ADA-Positive	0.0 Percentage of participants	0.3 Percentage of participants	—

Adverse Events

A: Faricimab 6 mg Q8W

Serious events: 111 serious events

Other events: 161 other events

Deaths: 16 deaths

B: Faricimab 6 mg PTI

Serious events: 117 serious events

Other events: 163 other events

Deaths: 21 deaths

C: Aflibercept 2 mg Q8W

Serious events: 93 serious events

Other events: 163 other events

Deaths: 13 deaths

Serious adverse events

Other adverse events

Other adverse events
Measure	A: Faricimab 6 mg Q8W n=313 participants at risk Participants randomized to Arm A received 6 milligrams (mg) faricimab intravitreal (IVT) injections once every 4 weeks (Q4W) to Week 20, followed by 6 mg faricimab IVT injections once every 8 weeks (Q8W) to Week 96, followed by the final study visit at Week 100.	B: Faricimab 6 mg PTI n=313 participants at risk Participants randomized to Arm B received 6 milligrams (mg) faricimab intravitreal (IVT) injections Q4W to at least Week 12, followed by a personalized treatment interval (PTI) dosing of 6 mg faricimab IVT injections up to once every 16 weeks (Q16W) through Week 96, followed by the final study visit at Week 100.	C: Aflibercept 2 mg Q8W n=311 participants at risk Participants randomized to Arm C received 2 milligrams (mg) aflibercept intravitreal (IVT) injections Q4W to Week 16, followed by 2 mg aflibercept IVT injections Q8W to Week 96, followed by the final study visit at Week 100.
Eye disorders Vitreous detachment	6.4% 20/313 • Number of events 25 • From Baseline until Week 100 Adverse events (AEs) are reported for the safety population, which includes all participants who received at least one injection of active study drug (faricimab or aflibercept) in the study eye. For ocular AEs, the number of participants and events reported per term are combined totals of AEs that occurred in the study eye or the fellow eye.	7.3% 23/313 • Number of events 28 • From Baseline until Week 100 Adverse events (AEs) are reported for the safety population, which includes all participants who received at least one injection of active study drug (faricimab or aflibercept) in the study eye. For ocular AEs, the number of participants and events reported per term are combined totals of AEs that occurred in the study eye or the fellow eye.	4.2% 13/311 • Number of events 16 • From Baseline until Week 100 Adverse events (AEs) are reported for the safety population, which includes all participants who received at least one injection of active study drug (faricimab or aflibercept) in the study eye. For ocular AEs, the number of participants and events reported per term are combined totals of AEs that occurred in the study eye or the fellow eye.
Eye disorders Cataract	18.5% 58/313 • Number of events 84 • From Baseline until Week 100 Adverse events (AEs) are reported for the safety population, which includes all participants who received at least one injection of active study drug (faricimab or aflibercept) in the study eye. For ocular AEs, the number of participants and events reported per term are combined totals of AEs that occurred in the study eye or the fellow eye.	15.0% 47/313 • Number of events 65 • From Baseline until Week 100 Adverse events (AEs) are reported for the safety population, which includes all participants who received at least one injection of active study drug (faricimab or aflibercept) in the study eye. For ocular AEs, the number of participants and events reported per term are combined totals of AEs that occurred in the study eye or the fellow eye.	17.7% 55/311 • Number of events 82 • From Baseline until Week 100 Adverse events (AEs) are reported for the safety population, which includes all participants who received at least one injection of active study drug (faricimab or aflibercept) in the study eye. For ocular AEs, the number of participants and events reported per term are combined totals of AEs that occurred in the study eye or the fellow eye.
Eye disorders Conjunctival haemorrhage	8.0% 25/313 • Number of events 35 • From Baseline until Week 100 Adverse events (AEs) are reported for the safety population, which includes all participants who received at least one injection of active study drug (faricimab or aflibercept) in the study eye. For ocular AEs, the number of participants and events reported per term are combined totals of AEs that occurred in the study eye or the fellow eye.	10.5% 33/313 • Number of events 41 • From Baseline until Week 100 Adverse events (AEs) are reported for the safety population, which includes all participants who received at least one injection of active study drug (faricimab or aflibercept) in the study eye. For ocular AEs, the number of participants and events reported per term are combined totals of AEs that occurred in the study eye or the fellow eye.	7.7% 24/311 • Number of events 32 • From Baseline until Week 100 Adverse events (AEs) are reported for the safety population, which includes all participants who received at least one injection of active study drug (faricimab or aflibercept) in the study eye. For ocular AEs, the number of participants and events reported per term are combined totals of AEs that occurred in the study eye or the fellow eye.
Eye disorders Diabetic retinal oedema	6.4% 20/313 • Number of events 27 • From Baseline until Week 100 Adverse events (AEs) are reported for the safety population, which includes all participants who received at least one injection of active study drug (faricimab or aflibercept) in the study eye. For ocular AEs, the number of participants and events reported per term are combined totals of AEs that occurred in the study eye or the fellow eye.	9.3% 29/313 • Number of events 37 • From Baseline until Week 100 Adverse events (AEs) are reported for the safety population, which includes all participants who received at least one injection of active study drug (faricimab or aflibercept) in the study eye. For ocular AEs, the number of participants and events reported per term are combined totals of AEs that occurred in the study eye or the fellow eye.	10.6% 33/311 • Number of events 40 • From Baseline until Week 100 Adverse events (AEs) are reported for the safety population, which includes all participants who received at least one injection of active study drug (faricimab or aflibercept) in the study eye. For ocular AEs, the number of participants and events reported per term are combined totals of AEs that occurred in the study eye or the fellow eye.
Infections and infestations Nasopharyngitis	8.6% 27/313 • Number of events 31 • From Baseline until Week 100 Adverse events (AEs) are reported for the safety population, which includes all participants who received at least one injection of active study drug (faricimab or aflibercept) in the study eye. For ocular AEs, the number of participants and events reported per term are combined totals of AEs that occurred in the study eye or the fellow eye.	5.8% 18/313 • Number of events 23 • From Baseline until Week 100 Adverse events (AEs) are reported for the safety population, which includes all participants who received at least one injection of active study drug (faricimab or aflibercept) in the study eye. For ocular AEs, the number of participants and events reported per term are combined totals of AEs that occurred in the study eye or the fellow eye.	9.6% 30/311 • Number of events 39 • From Baseline until Week 100 Adverse events (AEs) are reported for the safety population, which includes all participants who received at least one injection of active study drug (faricimab or aflibercept) in the study eye. For ocular AEs, the number of participants and events reported per term are combined totals of AEs that occurred in the study eye or the fellow eye.
Vascular disorders Hypertension	7.0% 22/313 • Number of events 27 • From Baseline until Week 100 Adverse events (AEs) are reported for the safety population, which includes all participants who received at least one injection of active study drug (faricimab or aflibercept) in the study eye. For ocular AEs, the number of participants and events reported per term are combined totals of AEs that occurred in the study eye or the fellow eye.	10.2% 32/313 • Number of events 34 • From Baseline until Week 100 Adverse events (AEs) are reported for the safety population, which includes all participants who received at least one injection of active study drug (faricimab or aflibercept) in the study eye. For ocular AEs, the number of participants and events reported per term are combined totals of AEs that occurred in the study eye or the fellow eye.	11.6% 36/311 • Number of events 38 • From Baseline until Week 100 Adverse events (AEs) are reported for the safety population, which includes all participants who received at least one injection of active study drug (faricimab or aflibercept) in the study eye. For ocular AEs, the number of participants and events reported per term are combined totals of AEs that occurred in the study eye or the fellow eye.
Eye disorders Vitreous floaters	5.4% 17/313 • Number of events 25 • From Baseline until Week 100 Adverse events (AEs) are reported for the safety population, which includes all participants who received at least one injection of active study drug (faricimab or aflibercept) in the study eye. For ocular AEs, the number of participants and events reported per term are combined totals of AEs that occurred in the study eye or the fellow eye.	3.5% 11/313 • Number of events 13 • From Baseline until Week 100 Adverse events (AEs) are reported for the safety population, which includes all participants who received at least one injection of active study drug (faricimab or aflibercept) in the study eye. For ocular AEs, the number of participants and events reported per term are combined totals of AEs that occurred in the study eye or the fellow eye.	3.2% 10/311 • Number of events 13 • From Baseline until Week 100 Adverse events (AEs) are reported for the safety population, which includes all participants who received at least one injection of active study drug (faricimab or aflibercept) in the study eye. For ocular AEs, the number of participants and events reported per term are combined totals of AEs that occurred in the study eye or the fellow eye.
Infections and infestations Urinary tract infection	4.5% 14/313 • Number of events 23 • From Baseline until Week 100 Adverse events (AEs) are reported for the safety population, which includes all participants who received at least one injection of active study drug (faricimab or aflibercept) in the study eye. For ocular AEs, the number of participants and events reported per term are combined totals of AEs that occurred in the study eye or the fellow eye.	4.8% 15/313 • Number of events 17 • From Baseline until Week 100 Adverse events (AEs) are reported for the safety population, which includes all participants who received at least one injection of active study drug (faricimab or aflibercept) in the study eye. For ocular AEs, the number of participants and events reported per term are combined totals of AEs that occurred in the study eye or the fellow eye.	6.1% 19/311 • Number of events 22 • From Baseline until Week 100 Adverse events (AEs) are reported for the safety population, which includes all participants who received at least one injection of active study drug (faricimab or aflibercept) in the study eye. For ocular AEs, the number of participants and events reported per term are combined totals of AEs that occurred in the study eye or the fellow eye.
Injury, poisoning and procedural complications Fall	5.1% 16/313 • Number of events 16 • From Baseline until Week 100 Adverse events (AEs) are reported for the safety population, which includes all participants who received at least one injection of active study drug (faricimab or aflibercept) in the study eye. For ocular AEs, the number of participants and events reported per term are combined totals of AEs that occurred in the study eye or the fellow eye.	6.1% 19/313 • Number of events 20 • From Baseline until Week 100 Adverse events (AEs) are reported for the safety population, which includes all participants who received at least one injection of active study drug (faricimab or aflibercept) in the study eye. For ocular AEs, the number of participants and events reported per term are combined totals of AEs that occurred in the study eye or the fellow eye.	2.9% 9/311 • Number of events 9 • From Baseline until Week 100 Adverse events (AEs) are reported for the safety population, which includes all participants who received at least one injection of active study drug (faricimab or aflibercept) in the study eye. For ocular AEs, the number of participants and events reported per term are combined totals of AEs that occurred in the study eye or the fellow eye.
Investigations Intraocular pressure increased	5.4% 17/313 • Number of events 28 • From Baseline until Week 100 Adverse events (AEs) are reported for the safety population, which includes all participants who received at least one injection of active study drug (faricimab or aflibercept) in the study eye. For ocular AEs, the number of participants and events reported per term are combined totals of AEs that occurred in the study eye or the fellow eye.	4.2% 13/313 • Number of events 25 • From Baseline until Week 100 Adverse events (AEs) are reported for the safety population, which includes all participants who received at least one injection of active study drug (faricimab or aflibercept) in the study eye. For ocular AEs, the number of participants and events reported per term are combined totals of AEs that occurred in the study eye or the fellow eye.	3.5% 11/311 • Number of events 13 • From Baseline until Week 100 Adverse events (AEs) are reported for the safety population, which includes all participants who received at least one injection of active study drug (faricimab or aflibercept) in the study eye. For ocular AEs, the number of participants and events reported per term are combined totals of AEs that occurred in the study eye or the fellow eye.

Additional Information

Medical Communications

Hoffmann-La Roche

Phone: 800-821-8590

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee The Study being conducted under this Agreement is part of the Overall Study. Investigator is free to publish in reputable journals or to present at professional conferences the results of the Study, but only after the first publication or presentation that involves the Overall Study. The Sponsor may request that Confidential Information be deleted and/or the publication be postponed in order to protect the Sponsor's intellectual property rights.
Publication restrictions are in place

Restriction type: OTHER