Trial Outcomes & Findings for Efficacy and Safety of LYR-210 for the Treatment of Chronic Rhinosinusitis in Adults (ENLIGHTEN 2) (NCT NCT05295459)

Last Updated: 2026-02-19

Results Overview

The 3CS are nasal blockage/obstruction/congestion, anterior/posterior nasal discharge, and facial pain/pressure. The diary is completed daily by study participants throughout the study. Each symptom is rated on a 4-point (0-3) scale where 0= none/absent symptoms, 1=mild symptoms, 2=moderate symptoms, and 3=severe symptoms. The composite score of 3CS is the sum of the three cardinal symptom scores. The 3CS total score ranges from 0-9, with higher scores indicating worse symptoms.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

182 participants

Primary outcome timeframe

Week 24

Results posted on

2026-02-19

Participant Flow

Week 24 Treatment Period: 2:1 (LYR-210 to Sham) Randomization

Participant milestones

Participant milestones
Measure	LYR-210 Single administration of LYR-210 drug matrix (7500 μg) LYR-210: LYR-210 drug matrix (mometasone furoate) Background therapy: Daily Saline Irrigation	Sham Procedure Control Single mock administration procedure Sham procedure control: Sham procedure control Background therapy: Daily Saline Irrigation
Overall Study STARTED	121	61
Overall Study COMPLETED	99	58
Overall Study NOT COMPLETED	22	3

Reasons for withdrawal

Reasons for withdrawal
Measure	LYR-210 Single administration of LYR-210 drug matrix (7500 μg) LYR-210: LYR-210 drug matrix (mometasone furoate) Background therapy: Daily Saline Irrigation	Sham Procedure Control Single mock administration procedure Sham procedure control: Sham procedure control Background therapy: Daily Saline Irrigation
Overall Study Treatment administration failure/procedure not attempted	10	0
Overall Study Withdrawal by Subject	6	2
Overall Study Adverse Event	2	0
Overall Study Lost to Follow-up	4	0
Overall Study Sinonasal surgery	0	1

Baseline Characteristics

ITT Analysis Set

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	LYR-210 n=111 Participants Single administration of LYR-210 drug matrix (7500 μg) LYR-210: LYR-210 drug matrix (mometasone furoate) Background therapy: Daily Saline Irrigation	Sham Procedure Control n=61 Participants Single mock administration procedure Sham procedure control: Sham procedure control Background therapy: Daily Saline Irrigation	Total n=172 Participants Total of all reporting groups
Age, Categorical <=18 years	1 Participants n=111 Participants • ITT Analysis Set	0 Participants n=61 Participants • ITT Analysis Set	1 Participants n=172 Participants • ITT Analysis Set
Age, Categorical Between 18 and 65 years	89 Participants n=111 Participants • ITT Analysis Set	57 Participants n=61 Participants • ITT Analysis Set	146 Participants n=172 Participants • ITT Analysis Set
Age, Categorical >=65 years	21 Participants n=111 Participants • ITT Analysis Set	4 Participants n=61 Participants • ITT Analysis Set	25 Participants n=172 Participants • ITT Analysis Set
Age, Continuous	50 Years STANDARD_DEVIATION 15.50 • n=111 Participants • ITT Analysis Set	49 Years STANDARD_DEVIATION 12.99 • n=61 Participants • ITT Analysis Set	50 Years STANDARD_DEVIATION 14.65 • n=172 Participants • ITT Analysis Set
Sex: Female, Male Female	46 Participants n=111 Participants • ITT Analysis Set	30 Participants n=61 Participants • ITT Analysis Set	76 Participants n=172 Participants • ITT Analysis Set
Sex: Female, Male Male	65 Participants n=111 Participants • ITT Analysis Set	31 Participants n=61 Participants • ITT Analysis Set	96 Participants n=172 Participants • ITT Analysis Set
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=111 Participants • ITT Analysis Set	0 Participants n=61 Participants • ITT Analysis Set	0 Participants n=172 Participants • ITT Analysis Set
Race (NIH/OMB) Asian	4 Participants n=111 Participants • ITT Analysis Set	4 Participants n=61 Participants • ITT Analysis Set	8 Participants n=172 Participants • ITT Analysis Set
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	1 Participants n=111 Participants • ITT Analysis Set	0 Participants n=61 Participants • ITT Analysis Set	1 Participants n=172 Participants • ITT Analysis Set
Race (NIH/OMB) Black or African American	9 Participants n=111 Participants • ITT Analysis Set	5 Participants n=61 Participants • ITT Analysis Set	14 Participants n=172 Participants • ITT Analysis Set
Race (NIH/OMB) White	94 Participants n=111 Participants • ITT Analysis Set	51 Participants n=61 Participants • ITT Analysis Set	145 Participants n=172 Participants • ITT Analysis Set
Race (NIH/OMB) More than one race	3 Participants n=111 Participants • ITT Analysis Set	1 Participants n=61 Participants • ITT Analysis Set	4 Participants n=172 Participants • ITT Analysis Set
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=111 Participants • ITT Analysis Set	0 Participants n=61 Participants • ITT Analysis Set	0 Participants n=172 Participants • ITT Analysis Set
Ethnicity (NIH/OMB) Hispanic or Latino	8 Participants n=111 Participants • ITT Analysis Set	4 Participants n=61 Participants • ITT Analysis Set	12 Participants n=172 Participants • ITT Analysis Set
Ethnicity (NIH/OMB) Not Hispanic or Latino	102 Participants n=111 Participants • ITT Analysis Set	57 Participants n=61 Participants • ITT Analysis Set	159 Participants n=172 Participants • ITT Analysis Set
Ethnicity (NIH/OMB) Unknown or Not Reported	1 Participants n=111 Participants • ITT Analysis Set	0 Participants n=61 Participants • ITT Analysis Set	1 Participants n=172 Participants • ITT Analysis Set
Region of Enrollment Belgium	2 Participants n=111 Participants • ITT Analysis Set	0 Participants n=61 Participants • ITT Analysis Set	2 Participants n=172 Participants • ITT Analysis Set
Region of Enrollment Bulgaria	13 Participants n=111 Participants • ITT Analysis Set	8 Participants n=61 Participants • ITT Analysis Set	21 Participants n=172 Participants • ITT Analysis Set
Region of Enrollment Germany	16 Participants n=111 Participants • ITT Analysis Set	10 Participants n=61 Participants • ITT Analysis Set	26 Participants n=172 Participants • ITT Analysis Set
Region of Enrollment Hungary	9 Participants n=111 Participants • ITT Analysis Set	8 Participants n=61 Participants • ITT Analysis Set	17 Participants n=172 Participants • ITT Analysis Set
Region of Enrollment Poland	8 Participants n=111 Participants • ITT Analysis Set	4 Participants n=61 Participants • ITT Analysis Set	12 Participants n=172 Participants • ITT Analysis Set
Region of Enrollment United States	63 Participants n=111 Participants • ITT Analysis Set	31 Participants n=61 Participants • ITT Analysis Set	94 Participants n=172 Participants • ITT Analysis Set
Baseline 3CS Score	6.46 Score STANDARD_DEVIATION 1.337 • n=94 Participants • The primary endpoint measure is based on the ITT Analysis Set without Nasal Polyps	7.31 Score STANDARD_DEVIATION 1.415 • n=49 Participants • The primary endpoint measure is based on the ITT Analysis Set without Nasal Polyps	6.75 Score STANDARD_DEVIATION 1.364 • n=143 Participants • The primary endpoint measure is based on the ITT Analysis Set without Nasal Polyps
Baseline SNOT-22 Total Score	56.2 Score STANDARD_DEVIATION 17.38 • n=111 Participants	58.8 Score STANDARD_DEVIATION 22.21 • n=61 Participants	57.1 Score STANDARD_DEVIATION 19.09 • n=172 Participants

PRIMARY outcome

Timeframe: Week 24

Population: ITT Analysis Set Without Nasal Polyps

Outcome measures

Outcome measures
Measure	LYR-210 n=94 Participants Single administration of LYR-210 drug matrix (7500 μg) LYR-210: LYR-210 drug matrix (mometasone furoate) Background therapy: Daily Saline Irrigation	Sham Procedure Control n=49 Participants Single mock administration procedure Sham procedure control: Sham procedure control Background therapy: Daily Saline Irrigation
Change From Baseline (CFBL) in the 7-day Average Composite Score of 3 Cardinal Symptoms (3CS) in Participants Without Nasal Polyps	-2.73 Change from Baseline in 3CS Score Standard Error 0.239	-1.61 Change from Baseline in 3CS Score Standard Error 0.332

SECONDARY outcome

Timeframe: Week 24

Population: ITT Analysis Set

Outcome measures

Outcome measures
Measure	LYR-210 n=111 Participants Single administration of LYR-210 drug matrix (7500 μg) LYR-210: LYR-210 drug matrix (mometasone furoate) Background therapy: Daily Saline Irrigation	Sham Procedure Control n=61 Participants Single mock administration procedure Sham procedure control: Sham procedure control Background therapy: Daily Saline Irrigation
CFBL in the 7-day Average Composite Score of 3CS in All Participants at Week 24	-2.62 Change from Baseline in 3CS Score Standard Error 0.229	-1.72 Change from Baseline in 3CS Score Standard Error 0.305

SECONDARY outcome

Timeframe: Week 24

Population: ITT Analysis Set

The SNOT-22 questionnaire is a 22-item disease-specific quality of life instrument. Each symptom is scored on a 6-point scale where 0 = no problem and 5 = problem as bad as it can be. The total SNOT-22 score is the sum of the 22 items and can range from 0 to 110 with higher scores indicating worse symptoms.

Outcome measures

Outcome measures
Measure	LYR-210 n=111 Participants Single administration of LYR-210 drug matrix (7500 μg) LYR-210: LYR-210 drug matrix (mometasone furoate) Background therapy: Daily Saline Irrigation	Sham Procedure Control n=61 Participants Single mock administration procedure Sham procedure control: Sham procedure control Background therapy: Daily Saline Irrigation
CFBL in the 22-item Sino-Nasal Outcome Test (SNOT-22) Total Score at Week 24	-22.4 Change from Baseline in SNOT-22 Score Standard Error 2.05	-13.7 Change from Baseline in SNOT-22 Score Standard Error 2.61

SECONDARY outcome

Timeframe: Week 20

Population: ITT Analysis Set

Change from baseline in the percent opacification of the bilateral anterior and posterior ethmoids at Week 20, as determined by 3-D volumetric CT analysis. 3-D volumetric scoring involves evaluations of each slice of 3-D coronal CT sequences and summing of all the slices to create a volumetric score ranging from 0% to 100%. A negative change from Baseline indicates improvement from Baseline.

Outcome measures

Outcome measures
Measure	LYR-210 n=111 Participants Single administration of LYR-210 drug matrix (7500 μg) LYR-210: LYR-210 drug matrix (mometasone furoate) Background therapy: Daily Saline Irrigation	Sham Procedure Control n=61 Participants Single mock administration procedure Sham procedure control: Sham procedure control Background therapy: Daily Saline Irrigation
CFBL in the 3-D Volumetric CT Score at Week 20	-2.70 Percent ethmoid opacification Standard Error 0.962	-0.55 Percent ethmoid opacification Standard Error 1.271

SECONDARY outcome

Timeframe: Week 24

Population: ITT Analysis Set

Number and percent of participants requiring rescue treatment (systemic corticosteroid for any reason or participants that were recommended/underwent sinonasal surgery) through Week 24.

Outcome measures

Outcome measures
Measure	LYR-210 n=111 Participants Single administration of LYR-210 drug matrix (7500 μg) LYR-210: LYR-210 drug matrix (mometasone furoate) Background therapy: Daily Saline Irrigation	Sham Procedure Control n=61 Participants Single mock administration procedure Sham procedure control: Sham procedure control Background therapy: Daily Saline Irrigation
Rescue Treatment Requirement Through Week 24	12 Participants	7 Participants

Adverse Events

LYR-210

Serious events: 2 serious events

Other events: 48 other events

Deaths: 0 deaths

Sham Procedure Control

Serious events: 0 serious events

Other events: 17 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	LYR-210 n=112 participants at risk The Safety Analysis Set included all randomized participants who successfully received the IP (LYR-210 or sham) on Day 1.	Sham Procedure Control n=60 participants at risk The Safety Analysis Set included all randomized participants who successfully received the IP (LYR-210 or sham) on Day 1.
Musculoskeletal and connective tissue disorders Lumbar spinal stenosis	0.89% 1/112 • Number of events 1 • Adverse Events are reported from the time the informed consent form is signed until completion of all follow-up visits, up to Week 24. 172 participants successfully received treatment. 10 participants who had a treatment administration failure are not included. One participant was randomized to sham but received LYR-210 in error; this participant was counted under LYR-210 for the Safety Analysis Set.	0.00% 0/60 • Adverse Events are reported from the time the informed consent form is signed until completion of all follow-up visits, up to Week 24. 172 participants successfully received treatment. 10 participants who had a treatment administration failure are not included. One participant was randomized to sham but received LYR-210 in error; this participant was counted under LYR-210 for the Safety Analysis Set.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Colon adenoma	0.89% 1/112 • Number of events 1 • Adverse Events are reported from the time the informed consent form is signed until completion of all follow-up visits, up to Week 24. 172 participants successfully received treatment. 10 participants who had a treatment administration failure are not included. One participant was randomized to sham but received LYR-210 in error; this participant was counted under LYR-210 for the Safety Analysis Set.	0.00% 0/60 • Adverse Events are reported from the time the informed consent form is signed until completion of all follow-up visits, up to Week 24. 172 participants successfully received treatment. 10 participants who had a treatment administration failure are not included. One participant was randomized to sham but received LYR-210 in error; this participant was counted under LYR-210 for the Safety Analysis Set.
Nervous system disorders Transient ischaemic attack	0.89% 1/112 • Number of events 1 • Adverse Events are reported from the time the informed consent form is signed until completion of all follow-up visits, up to Week 24. 172 participants successfully received treatment. 10 participants who had a treatment administration failure are not included. One participant was randomized to sham but received LYR-210 in error; this participant was counted under LYR-210 for the Safety Analysis Set.	0.00% 0/60 • Adverse Events are reported from the time the informed consent form is signed until completion of all follow-up visits, up to Week 24. 172 participants successfully received treatment. 10 participants who had a treatment administration failure are not included. One participant was randomized to sham but received LYR-210 in error; this participant was counted under LYR-210 for the Safety Analysis Set.

Other adverse events

Other adverse events
Measure	LYR-210 n=112 participants at risk The Safety Analysis Set included all randomized participants who successfully received the IP (LYR-210 or sham) on Day 1.	Sham Procedure Control n=60 participants at risk The Safety Analysis Set included all randomized participants who successfully received the IP (LYR-210 or sham) on Day 1.
Infections and infestations Acute sinusitis	8.9% 10/112 • Number of events 12 • Adverse Events are reported from the time the informed consent form is signed until completion of all follow-up visits, up to Week 24. 172 participants successfully received treatment. 10 participants who had a treatment administration failure are not included. One participant was randomized to sham but received LYR-210 in error; this participant was counted under LYR-210 for the Safety Analysis Set.	3.3% 2/60 • Number of events 3 • Adverse Events are reported from the time the informed consent form is signed until completion of all follow-up visits, up to Week 24. 172 participants successfully received treatment. 10 participants who had a treatment administration failure are not included. One participant was randomized to sham but received LYR-210 in error; this participant was counted under LYR-210 for the Safety Analysis Set.
Infections and infestations COVID-19	4.5% 5/112 • Number of events 5 • Adverse Events are reported from the time the informed consent form is signed until completion of all follow-up visits, up to Week 24. 172 participants successfully received treatment. 10 participants who had a treatment administration failure are not included. One participant was randomized to sham but received LYR-210 in error; this participant was counted under LYR-210 for the Safety Analysis Set.	6.7% 4/60 • Number of events 4 • Adverse Events are reported from the time the informed consent form is signed until completion of all follow-up visits, up to Week 24. 172 participants successfully received treatment. 10 participants who had a treatment administration failure are not included. One participant was randomized to sham but received LYR-210 in error; this participant was counted under LYR-210 for the Safety Analysis Set.
Infections and infestations Chronic sinusitis	7.1% 8/112 • Number of events 10 • Adverse Events are reported from the time the informed consent form is signed until completion of all follow-up visits, up to Week 24. 172 participants successfully received treatment. 10 participants who had a treatment administration failure are not included. One participant was randomized to sham but received LYR-210 in error; this participant was counted under LYR-210 for the Safety Analysis Set.	10.0% 6/60 • Number of events 8 • Adverse Events are reported from the time the informed consent form is signed until completion of all follow-up visits, up to Week 24. 172 participants successfully received treatment. 10 participants who had a treatment administration failure are not included. One participant was randomized to sham but received LYR-210 in error; this participant was counted under LYR-210 for the Safety Analysis Set.
Infections and infestations Nasopharyngitis	6.2% 7/112 • Number of events 8 • Adverse Events are reported from the time the informed consent form is signed until completion of all follow-up visits, up to Week 24. 172 participants successfully received treatment. 10 participants who had a treatment administration failure are not included. One participant was randomized to sham but received LYR-210 in error; this participant was counted under LYR-210 for the Safety Analysis Set.	6.7% 4/60 • Number of events 4 • Adverse Events are reported from the time the informed consent form is signed until completion of all follow-up visits, up to Week 24. 172 participants successfully received treatment. 10 participants who had a treatment administration failure are not included. One participant was randomized to sham but received LYR-210 in error; this participant was counted under LYR-210 for the Safety Analysis Set.
Infections and infestations Upper respiratory tract infection	8.9% 10/112 • Number of events 11 • Adverse Events are reported from the time the informed consent form is signed until completion of all follow-up visits, up to Week 24. 172 participants successfully received treatment. 10 participants who had a treatment administration failure are not included. One participant was randomized to sham but received LYR-210 in error; this participant was counted under LYR-210 for the Safety Analysis Set.	8.3% 5/60 • Number of events 5 • Adverse Events are reported from the time the informed consent form is signed until completion of all follow-up visits, up to Week 24. 172 participants successfully received treatment. 10 participants who had a treatment administration failure are not included. One participant was randomized to sham but received LYR-210 in error; this participant was counted under LYR-210 for the Safety Analysis Set.
Nervous system disorders Headache	5.4% 6/112 • Number of events 6 • Adverse Events are reported from the time the informed consent form is signed until completion of all follow-up visits, up to Week 24. 172 participants successfully received treatment. 10 participants who had a treatment administration failure are not included. One participant was randomized to sham but received LYR-210 in error; this participant was counted under LYR-210 for the Safety Analysis Set.	5.0% 3/60 • Number of events 3 • Adverse Events are reported from the time the informed consent form is signed until completion of all follow-up visits, up to Week 24. 172 participants successfully received treatment. 10 participants who had a treatment administration failure are not included. One participant was randomized to sham but received LYR-210 in error; this participant was counted under LYR-210 for the Safety Analysis Set.
Respiratory, thoracic and mediastinal disorders Epistaxis	16.1% 18/112 • Number of events 22 • Adverse Events are reported from the time the informed consent form is signed until completion of all follow-up visits, up to Week 24. 172 participants successfully received treatment. 10 participants who had a treatment administration failure are not included. One participant was randomized to sham but received LYR-210 in error; this participant was counted under LYR-210 for the Safety Analysis Set.	1.7% 1/60 • Number of events 1 • Adverse Events are reported from the time the informed consent form is signed until completion of all follow-up visits, up to Week 24. 172 participants successfully received treatment. 10 participants who had a treatment administration failure are not included. One participant was randomized to sham but received LYR-210 in error; this participant was counted under LYR-210 for the Safety Analysis Set.

Additional Information

Senior Vice President, Clinical Affairs

Lyra Therapeutics

Phone: 617-393-4600

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee Except as approved by Sponsor, single center data will not be published before multicenter data, unless \>1 year has elapsed since completion of the Study. PI may publish single center data provided that PI shall: i) provide a copy of the publication to Sponsor at least 60 days in advance of submission for publication; ii) delete Sponsor Confidential Information and make other reasonable changes; and iii) delay submission by up to 90 additional days to permit intellectual property filings.
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Restriction type: OTHER