Trial Outcomes & Findings for HELIOS-A: A Study of Vutrisiran (ALN-TTRSC02) in Patients With Hereditary Transthyretin Amyloidosis (hATTR Amyloidosis) (NCT NCT03759379)

Last Updated: 2026-01-12

Results Overview

The mNIS+7 is a composite score that measures neurologic impairment which includes the following components: physical exam of lower limbs, upper limbs and cranial nerves to assess motor strength/weakness, electrophysiologic measurement of small and large nerve fiber function, sensory testing and postural blood pressure. The mNIS+7 is scored from 0 (no impairment) to 304 points (maximum impairment). A higher score indicates a worse outcome.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

164 participants

Primary outcome timeframe

Baseline, Month 9

Results posted on

2026-01-12

Participant Flow

Participants with hATTR amyloidosis were enrolled and treated at 57 sites in Argentina, Australia, Belgium, Brazil, Bulgaria, Canada, Cyprus, France, Germany, Greece, Italy, Japan, Korea, Malaysia, Mexico, Netherlands, Portugal, Spain, Sweden, Taiwan, United Kingdom and United States. Data is reported for the 9-Month primary analysis period.

This study will use the placebo arm of the APOLLO study (NCT01960348) as an external comparator for the primary and most other efficacy endpoints (N=77).

Participant milestones

Participant milestones
Measure	Vutrisiran + Vutrisiran (HELIOS-A) Participants will receive vutrisiran 25 mg subcutaneous (SC) injection once every 3 months (q3M) for 18 months during the Treatment Period followed by vutrisiran SC injection once every 6 months (q6M) or q3M during the Randomized Treatment Extension (RTE) Period.	Patisiran + Vutrisiran (HELIOS-A) Participants will receive patisiran 0.3 mg/kg intravenous (IV) infusion once every 3 weeks (q3w) for 18 months during the Treatment Period followed by vutrisiran SC injection q6M or q3M during the RTE Period.
Treatment Period STARTED	122	42
Treatment Period COMPLETED	0	0
Treatment Period NOT COMPLETED	122	42
Randomized Treatment Extension Period STARTED	0	0
Randomized Treatment Extension Period COMPLETED	0	0
Randomized Treatment Extension Period NOT COMPLETED	0	0

Reasons for withdrawal

Reasons for withdrawal
Measure	Vutrisiran + Vutrisiran (HELIOS-A) Participants will receive vutrisiran 25 mg subcutaneous (SC) injection once every 3 months (q3M) for 18 months during the Treatment Period followed by vutrisiran SC injection once every 6 months (q6M) or q3M during the Randomized Treatment Extension (RTE) Period.	Patisiran + Vutrisiran (HELIOS-A) Participants will receive patisiran 0.3 mg/kg intravenous (IV) infusion once every 3 weeks (q3w) for 18 months during the Treatment Period followed by vutrisiran SC injection q6M or q3M during the RTE Period.
Treatment Period Remained in this Period at Time of Data Cut	119	38
Treatment Period Death	2	3
Treatment Period Lost to Follow-up	1	0
Treatment Period Physician Decision	0	1

Baseline Characteristics

Baseline characteristics data from the external placebo arm of the APOLLO study was not summarized with the data from HELIOS-A. APOLLO placebo data was only used as an external comparator for the primary and most other efficacy endpoints. Therefore APOLLO placebo baseline characteristic data is reported separately directly below.

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	External Placebo Comparator (APOLLO) n=77 Participants Participants in the APOLLO study (NCT01960348) who received at least 1 dose of placebo.	Vutrisiran + Vutrisiran (HELIOS-A) n=122 Participants Participants will receive vutrisiran 25 mg SC injection q3M for 18 months during the Treatment Period followed by vutrisiran SC injection q6M or q3M during the RTE Period.	Patisiran + Vutrisiran (HELIOS-A) n=42 Participants Participants will receive patisiran 0.3 mg/kg IV infusion q3w for 18 months during the Treatment Period followed by vutrisiran SC injection q6M or q3M during the RTE Period.	Total n=241 Participants Total of all reporting groups
Age, Continuous	62.2 years STANDARD_DEVIATION 10.76 • n=77 Participants • Baseline characteristics data from the external placebo arm of the APOLLO study was not summarized with the data from HELIOS-A. APOLLO placebo data was only used as an external comparator for the primary and most other efficacy endpoints. Therefore APOLLO placebo baseline characteristic data is reported separately.	57.8 years STANDARD_DEVIATION 13.2 • n=122 Participants • Baseline characteristics data from the external placebo arm of the APOLLO study was not summarized with the data from HELIOS-A. APOLLO placebo data was only used as an external comparator for the primary and most other efficacy endpoints. Therefore APOLLO placebo baseline characteristic data is reported separately directly below.	58.0 years STANDARD_DEVIATION 10.5 • n=42 Participants • Baseline characteristics data from the external placebo arm of the APOLLO study was not summarized with the data from HELIOS-A. APOLLO placebo data was only used as an external comparator for the primary and most other efficacy endpoints. Therefore APOLLO placebo baseline characteristic data is reported separately directly below.	62.2 years STANDARD_DEVIATION 10.76 • n=77 Participants • Baseline characteristics data from the external placebo arm of the APOLLO study was not summarized with the data from HELIOS-A. APOLLO placebo data was only used as an external comparator for the primary and most other efficacy endpoints. Therefore APOLLO placebo baseline characteristic data is reported separately.
Sex: Female, Male Female	19 Participants n=77 Participants • Baseline characteristics data from the external placebo arm of the APOLLO study was not summarized with the data from HELIOS-A. APOLLO placebo data was only used as an external comparator for the primary and most other efficacy endpoints. Therefore APOLLO placebo baseline characteristic data is reported separately.	43 Participants n=122 Participants • Baseline characteristics data from the external placebo arm of the APOLLO study was not summarized with the data from HELIOS-A. APOLLO placebo data was only used as an external comparator for the primary and most other efficacy endpoints. Therefore APOLLO placebo baseline characteristic data is reported separately directly below.	15 Participants n=42 Participants • Baseline characteristics data from the external placebo arm of the APOLLO study was not summarized with the data from HELIOS-A. APOLLO placebo data was only used as an external comparator for the primary and most other efficacy endpoints. Therefore APOLLO placebo baseline characteristic data is reported separately directly below.	19 Participants n=77 Participants • Baseline characteristics data from the external placebo arm of the APOLLO study was not summarized with the data from HELIOS-A. APOLLO placebo data was only used as an external comparator for the primary and most other efficacy endpoints. Therefore APOLLO placebo baseline characteristic data is reported separately.
Sex: Female, Male Male	58 Participants n=77 Participants • Baseline characteristics data from the external placebo arm of the APOLLO study was not summarized with the data from HELIOS-A. APOLLO placebo data was only used as an external comparator for the primary and most other efficacy endpoints. Therefore APOLLO placebo baseline characteristic data is reported separately.	79 Participants n=122 Participants • Baseline characteristics data from the external placebo arm of the APOLLO study was not summarized with the data from HELIOS-A. APOLLO placebo data was only used as an external comparator for the primary and most other efficacy endpoints. Therefore APOLLO placebo baseline characteristic data is reported separately directly below.	27 Participants n=42 Participants • Baseline characteristics data from the external placebo arm of the APOLLO study was not summarized with the data from HELIOS-A. APOLLO placebo data was only used as an external comparator for the primary and most other efficacy endpoints. Therefore APOLLO placebo baseline characteristic data is reported separately directly below.	58 Participants n=77 Participants • Baseline characteristics data from the external placebo arm of the APOLLO study was not summarized with the data from HELIOS-A. APOLLO placebo data was only used as an external comparator for the primary and most other efficacy endpoints. Therefore APOLLO placebo baseline characteristic data is reported separately.
Race/Ethnicity, Customized Asian	25 Participants n=77 Participants • Baseline characteristics data from the external placebo arm of the APOLLO study was not summarized with the data from HELIOS-A. APOLLO placebo data was only used as an external comparator for the primary and most other efficacy endpoints. Therefore APOLLO placebo baseline characteristic data is reported separately.	21 Participants n=122 Participants • Baseline characteristics data from the external placebo arm of the APOLLO study was not summarized with the data from HELIOS-A. APOLLO placebo data was only used as an external comparator for the primary and most other efficacy endpoints. Therefore APOLLO placebo baseline characteristic data is reported separately directly below.	8 Participants n=42 Participants • Baseline characteristics data from the external placebo arm of the APOLLO study was not summarized with the data from HELIOS-A. APOLLO placebo data was only used as an external comparator for the primary and most other efficacy endpoints. Therefore APOLLO placebo baseline characteristic data is reported separately directly below.	25 Participants n=77 Participants • Baseline characteristics data from the external placebo arm of the APOLLO study was not summarized with the data from HELIOS-A. APOLLO placebo data was only used as an external comparator for the primary and most other efficacy endpoints. Therefore APOLLO placebo baseline characteristic data is reported separately.
Race/Ethnicity, Customized Black or African American	1 Participants n=77 Participants • Baseline characteristics data from the external placebo arm of the APOLLO study was not summarized with the data from HELIOS-A. APOLLO placebo data was only used as an external comparator for the primary and most other efficacy endpoints. Therefore APOLLO placebo baseline characteristic data is reported separately.	4 Participants n=122 Participants • Baseline characteristics data from the external placebo arm of the APOLLO study was not summarized with the data from HELIOS-A. APOLLO placebo data was only used as an external comparator for the primary and most other efficacy endpoints. Therefore APOLLO placebo baseline characteristic data is reported separately directly below.	4 Participants n=42 Participants • Baseline characteristics data from the external placebo arm of the APOLLO study was not summarized with the data from HELIOS-A. APOLLO placebo data was only used as an external comparator for the primary and most other efficacy endpoints. Therefore APOLLO placebo baseline characteristic data is reported separately directly below.	1 Participants n=77 Participants • Baseline characteristics data from the external placebo arm of the APOLLO study was not summarized with the data from HELIOS-A. APOLLO placebo data was only used as an external comparator for the primary and most other efficacy endpoints. Therefore APOLLO placebo baseline characteristic data is reported separately.
Race/Ethnicity, Customized Multiple	0 Participants Baseline characteristics data from the external placebo arm of the APOLLO study was not summarized with the data from HELIOS-A. APOLLO placebo data was only used as an external comparator for the primary and most other efficacy endpoints. Therefore APOLLO placebo baseline characteristic data is reported separately directly below.	1 Participants n=122 Participants • Baseline characteristics data from the external placebo arm of the APOLLO study was not summarized with the data from HELIOS-A. APOLLO placebo data was only used as an external comparator for the primary and most other efficacy endpoints. Therefore APOLLO placebo baseline characteristic data is reported separately directly below.	0 Participants n=42 Participants • Baseline characteristics data from the external placebo arm of the APOLLO study was not summarized with the data from HELIOS-A. APOLLO placebo data was only used as an external comparator for the primary and most other efficacy endpoints. Therefore APOLLO placebo baseline characteristic data is reported separately directly below.	1 Participants n=164 Participants • Baseline characteristics data from the external placebo arm of the APOLLO study was not summarized with the data from HELIOS-A. APOLLO placebo data was only used as an external comparator for the primary and most other efficacy endpoints. Therefore APOLLO placebo baseline characteristic data is reported separately directly below.
Race/Ethnicity, Customized Other	0 Participants Baseline characteristics data from the external placebo arm of the APOLLO study was not summarized with the data from HELIOS-A. APOLLO placebo data was only used as an external comparator for the primary and most other efficacy endpoints. Therefore APOLLO placebo baseline characteristic data is reported separately directly below.	10 Participants n=122 Participants • Baseline characteristics data from the external placebo arm of the APOLLO study was not summarized with the data from HELIOS-A. APOLLO placebo data was only used as an external comparator for the primary and most other efficacy endpoints. Therefore APOLLO placebo baseline characteristic data is reported separately directly below.	1 Participants n=42 Participants • Baseline characteristics data from the external placebo arm of the APOLLO study was not summarized with the data from HELIOS-A. APOLLO placebo data was only used as an external comparator for the primary and most other efficacy endpoints. Therefore APOLLO placebo baseline characteristic data is reported separately directly below.	11 Participants n=164 Participants • Baseline characteristics data from the external placebo arm of the APOLLO study was not summarized with the data from HELIOS-A. APOLLO placebo data was only used as an external comparator for the primary and most other efficacy endpoints. Therefore APOLLO placebo baseline characteristic data is reported separately directly below.
Race/Ethnicity, Customized Unknown	0 Participants Baseline characteristics data from the external placebo arm of the APOLLO study was not summarized with the data from HELIOS-A. APOLLO placebo data was only used as an external comparator for the primary and most other efficacy endpoints. Therefore APOLLO placebo baseline characteristic data is reported separately directly below.	0 Participants n=122 Participants • Baseline characteristics data from the external placebo arm of the APOLLO study was not summarized with the data from HELIOS-A. APOLLO placebo data was only used as an external comparator for the primary and most other efficacy endpoints. Therefore APOLLO placebo baseline characteristic data is reported separately directly below.	0 Participants n=42 Participants • Baseline characteristics data from the external placebo arm of the APOLLO study was not summarized with the data from HELIOS-A. APOLLO placebo data was only used as an external comparator for the primary and most other efficacy endpoints. Therefore APOLLO placebo baseline characteristic data is reported separately directly below.	0 Participants n=164 Participants • Baseline characteristics data from the external placebo arm of the APOLLO study was not summarized with the data from HELIOS-A. APOLLO placebo data was only used as an external comparator for the primary and most other efficacy endpoints. Therefore APOLLO placebo baseline characteristic data is reported separately directly below.
Race/Ethnicity, Customized White	50 Participants n=77 Participants • Baseline characteristics data from the external placebo arm of the APOLLO study was not summarized with the data from HELIOS-A. APOLLO placebo data was only used as an external comparator for the primary and most other efficacy endpoints. Therefore APOLLO placebo baseline characteristic data is reported separately.	86 Participants n=122 Participants • Baseline characteristics data from the external placebo arm of the APOLLO study was not summarized with the data from HELIOS-A. APOLLO placebo data was only used as an external comparator for the primary and most other efficacy endpoints. Therefore APOLLO placebo baseline characteristic data is reported separately directly below.	29 Participants n=42 Participants • Baseline characteristics data from the external placebo arm of the APOLLO study was not summarized with the data from HELIOS-A. APOLLO placebo data was only used as an external comparator for the primary and most other efficacy endpoints. Therefore APOLLO placebo baseline characteristic data is reported separately directly below.	50 Participants n=77 Participants • Baseline characteristics data from the external placebo arm of the APOLLO study was not summarized with the data from HELIOS-A. APOLLO placebo data was only used as an external comparator for the primary and most other efficacy endpoints. Therefore APOLLO placebo baseline characteristic data is reported separately.
Race/Ethnicity, Customized Unknown or Not Reported	1 Participants n=77 Participants • Baseline characteristics data from the external placebo arm of the APOLLO study was not summarized with the data from HELIOS-A. APOLLO placebo data was only used as an external comparator for the primary and most other efficacy endpoints. Therefore APOLLO placebo baseline characteristic data is reported separately.	—	—	1 Participants n=77 Participants • Baseline characteristics data from the external placebo arm of the APOLLO study was not summarized with the data from HELIOS-A. APOLLO placebo data was only used as an external comparator for the primary and most other efficacy endpoints. Therefore APOLLO placebo baseline characteristic data is reported separately.
Modified Neuropathy Impairment Score +7 (mNIS+7)	74.61 score on a scale STANDARD_DEVIATION 37.041 • n=77 Participants • Baseline characteristics data from the external placebo arm of the APOLLO study was not summarized with the data from HELIOS-A. APOLLO placebo data was only used as an external comparator for the primary and most other efficacy endpoints. Therefore APOLLO placebo baseline characteristic data is reported separately.	60.55 score on a scale STANDARD_DEVIATION 35.99 • n=122 Participants • Baseline characteristics data from the external placebo arm of the APOLLO study was not summarized with the data from HELIOS-A. APOLLO placebo data was only used as an external comparator for the primary and most other efficacy endpoints. Therefore APOLLO placebo baseline characteristic data is reported separately directly below.	57.69 score on a scale STANDARD_DEVIATION 33.71 • n=42 Participants • Baseline characteristics data from the external placebo arm of the APOLLO study was not summarized with the data from HELIOS-A. APOLLO placebo data was only used as an external comparator for the primary and most other efficacy endpoints. Therefore APOLLO placebo baseline characteristic data is reported separately directly below.	74.61 score on a scale STANDARD_DEVIATION 37.041 • n=77 Participants • Baseline characteristics data from the external placebo arm of the APOLLO study was not summarized with the data from HELIOS-A. APOLLO placebo data was only used as an external comparator for the primary and most other efficacy endpoints. Therefore APOLLO placebo baseline characteristic data is reported separately.

PRIMARY outcome

Timeframe: Baseline, Month 9

Population: Modified Intent-to-Treat (mITT) Population: All randomized participants who received any amount of study drug. Participants were analyzed according to the treatment to which they were randomized.

Outcome measures

Outcome measures
Measure	External Placebo Comparator (APOLLO) n=77 Participants Participants in the APOLLO study (NCT01960348) who received at least 1 dose of placebo.	Vutrisiran + Vutrisiran (HELIOS-A) n=122 Participants Participants will receive vutrisiran 25 mg subcutaneous (SC) injection once every 3 months (q3M) for 18 months during the Treatment Period followed by vutrisiran SC injection during the Randomized Treatment Extension (RTE) Period.
Change From Baseline in the Modified Neurologic Impairment Score +7 (mNIS+7) at Month 9 Between the Vutrisiran Group (HELIOS-A) and the External Placebo Comparator Group [APOLLO (NCT01960348)]	14.76 score on a scale Standard Error 2.00	-2.24 score on a scale Standard Error 1.43

SECONDARY outcome

Timeframe: Baseline, Month 9

The Norfolk QoL-DN questionnaire is a standardized 35-item patient-reported outcomes measure that is sensitive to the different features of diabetic neuropathy - small fiber, large fiber, and autonomic nerve function. The total score ranges from -4 (best possible quality of life) to 136 points (worst possible quality of life). A higher score indicates a worse outcome.

Outcome measures

Outcome measures
Measure	External Placebo Comparator (APOLLO) n=77 Participants Participants in the APOLLO study (NCT01960348) who received at least 1 dose of placebo.	Vutrisiran + Vutrisiran (HELIOS-A) n=122 Participants Participants will receive vutrisiran 25 mg subcutaneous (SC) injection once every 3 months (q3M) for 18 months during the Treatment Period followed by vutrisiran SC injection during the Randomized Treatment Extension (RTE) Period.
Change From Baseline in Norfolk Quality of Life-Diabetic Neuropathy (Norfolk QoL-DN) Total Score at Month 9 Between the Vutrisiran Group (HELIOS-A) and the External Placebo Comparator Group [APOLLO (NCT01960348)]	12.9 score on a scale Standard Error 2.2	-3.3 score on a scale Standard Error 1.7

SECONDARY outcome

Timeframe: Baseline, Month 9

The 10-MWT is a measure of ambulatory ability and measures the time (in seconds) that it takes a participant to walk 10 meters (gait speed). An increase in gait speed from baseline represents improvement, and a decrease from baseline represents worsening.

Outcome measures

Outcome measures
Measure	External Placebo Comparator (APOLLO) n=77 Participants Participants in the APOLLO study (NCT01960348) who received at least 1 dose of placebo.	Vutrisiran + Vutrisiran (HELIOS-A) n=122 Participants Participants will receive vutrisiran 25 mg subcutaneous (SC) injection once every 3 months (q3M) for 18 months during the Treatment Period followed by vutrisiran SC injection during the Randomized Treatment Extension (RTE) Period.
Change From Baseline in the Timed 10-Meter Walk Test (10-MWT) at Month 9 Between the Vutrisiran Group (HELIOS-A) and the External Placebo Comparator Group [APOLLO (NCT01960348)]	-0.133 m/sec Standard Error 0.025	-0.001 m/sec Standard Error 0.019

SECONDARY outcome

Timeframe: Baseline, Month 18

The mNIS+7 is a composite score that quantifies motor, sensory, and autonomic neurologic impairment due to injury of large and small nerves. The mNIS+7 is scored from 0 (no impairment) to 304 points (maximum impairment). A higher score indicates a worse outcome.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Baseline, Month 18

Outcome measures

Outcome data not reported

Serious events: 17 serious events

Other events: 31 other events

Deaths: 3 deaths

Serious adverse events

Other adverse events

Additional Information

Chief Medical Officer

Alnylam Pharmaceuticals Inc.

Phone: 866-330-0326

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee It is intended that after completion of the study, the data are to be submitted for publication in a scientific journal and/or for reporting at a scientific meeting. A copy of any proposed publication (eg, manuscript, abstracts, oral/slide presentations, book chapters) based on this study, must be provided and confirmed/received at the Sponsor at least 30 days before its submission.
Publication restrictions are in place

Restriction type: OTHER

Measure	Vutrisiran + Vutrisiran (HELIOS-A) n=122 participants at risk Participants will receive vutrisiran 25 mg SC injection q3M for 18 months during the Treatment Period followed by vutrisiran SC injection q6M or q3M during the RTE Period.	Patisiran + Vutrisiran (HELIOS-A) n=42 participants at risk Participants will receive patisiran 0.3 mg/kg IV infusion q3w for 18 months during the Treatment Period followed by vutrisiran SC injection q6M or q3M during the RTE Period.
Gastrointestinal disorders Abdominal pain	5.7% 7/122 • Non-serious AEs from first dose of study drug through Month 9. SAEs from signing of informed consent through Month 9. Adverse events are provided for the vutrisiran group and the reference comparator (patisiran) group as of the data cutoff date (10 November 2020).	0.00% 0/42 • Non-serious AEs from first dose of study drug through Month 9. SAEs from signing of informed consent through Month 9. Adverse events are provided for the vutrisiran group and the reference comparator (patisiran) group as of the data cutoff date (10 November 2020).
Gastrointestinal disorders Constipation	3.3% 4/122 • Non-serious AEs from first dose of study drug through Month 9. SAEs from signing of informed consent through Month 9. Adverse events are provided for the vutrisiran group and the reference comparator (patisiran) group as of the data cutoff date (10 November 2020).	9.5% 4/42 • Non-serious AEs from first dose of study drug through Month 9. SAEs from signing of informed consent through Month 9. Adverse events are provided for the vutrisiran group and the reference comparator (patisiran) group as of the data cutoff date (10 November 2020).
Gastrointestinal disorders Diarrhoea	12.3% 15/122 • Non-serious AEs from first dose of study drug through Month 9. SAEs from signing of informed consent through Month 9. Adverse events are provided for the vutrisiran group and the reference comparator (patisiran) group as of the data cutoff date (10 November 2020).	9.5% 4/42 • Non-serious AEs from first dose of study drug through Month 9. SAEs from signing of informed consent through Month 9. Adverse events are provided for the vutrisiran group and the reference comparator (patisiran) group as of the data cutoff date (10 November 2020).
Gastrointestinal disorders Nausea	9.0% 11/122 • Non-serious AEs from first dose of study drug through Month 9. SAEs from signing of informed consent through Month 9. Adverse events are provided for the vutrisiran group and the reference comparator (patisiran) group as of the data cutoff date (10 November 2020).	9.5% 4/42 • Non-serious AEs from first dose of study drug through Month 9. SAEs from signing of informed consent through Month 9. Adverse events are provided for the vutrisiran group and the reference comparator (patisiran) group as of the data cutoff date (10 November 2020).
Gastrointestinal disorders Vomiting	5.7% 7/122 • Non-serious AEs from first dose of study drug through Month 9. SAEs from signing of informed consent through Month 9. Adverse events are provided for the vutrisiran group and the reference comparator (patisiran) group as of the data cutoff date (10 November 2020).	7.1% 3/42 • Non-serious AEs from first dose of study drug through Month 9. SAEs from signing of informed consent through Month 9. Adverse events are provided for the vutrisiran group and the reference comparator (patisiran) group as of the data cutoff date (10 November 2020).
General disorders Oedema peripheral	8.2% 10/122 • Non-serious AEs from first dose of study drug through Month 9. SAEs from signing of informed consent through Month 9. Adverse events are provided for the vutrisiran group and the reference comparator (patisiran) group as of the data cutoff date (10 November 2020).	9.5% 4/42 • Non-serious AEs from first dose of study drug through Month 9. SAEs from signing of informed consent through Month 9. Adverse events are provided for the vutrisiran group and the reference comparator (patisiran) group as of the data cutoff date (10 November 2020).
Immune system disorders Infusion related reaction	0.00% 0/122 • Non-serious AEs from first dose of study drug through Month 9. SAEs from signing of informed consent through Month 9. Adverse events are provided for the vutrisiran group and the reference comparator (patisiran) group as of the data cutoff date (10 November 2020).	21.4% 9/42 • Non-serious AEs from first dose of study drug through Month 9. SAEs from signing of informed consent through Month 9. Adverse events are provided for the vutrisiran group and the reference comparator (patisiran) group as of the data cutoff date (10 November 2020).
Infections and infestations Nasopharyngitis	6.6% 8/122 • Non-serious AEs from first dose of study drug through Month 9. SAEs from signing of informed consent through Month 9. Adverse events are provided for the vutrisiran group and the reference comparator (patisiran) group as of the data cutoff date (10 November 2020).	2.4% 1/42 • Non-serious AEs from first dose of study drug through Month 9. SAEs from signing of informed consent through Month 9. Adverse events are provided for the vutrisiran group and the reference comparator (patisiran) group as of the data cutoff date (10 November 2020).
Infections and infestations Upper respiratory tract infection	7.4% 9/122 • Non-serious AEs from first dose of study drug through Month 9. SAEs from signing of informed consent through Month 9. Adverse events are provided for the vutrisiran group and the reference comparator (patisiran) group as of the data cutoff date (10 November 2020).	9.5% 4/42 • Non-serious AEs from first dose of study drug through Month 9. SAEs from signing of informed consent through Month 9. Adverse events are provided for the vutrisiran group and the reference comparator (patisiran) group as of the data cutoff date (10 November 2020).
Infections and infestations Urinary tract infection	10.7% 13/122 • Non-serious AEs from first dose of study drug through Month 9. SAEs from signing of informed consent through Month 9. Adverse events are provided for the vutrisiran group and the reference comparator (patisiran) group as of the data cutoff date (10 November 2020).	11.9% 5/42 • Non-serious AEs from first dose of study drug through Month 9. SAEs from signing of informed consent through Month 9. Adverse events are provided for the vutrisiran group and the reference comparator (patisiran) group as of the data cutoff date (10 November 2020).
Injury, poisoning and procedural complications Fall	9.8% 12/122 • Non-serious AEs from first dose of study drug through Month 9. SAEs from signing of informed consent through Month 9. Adverse events are provided for the vutrisiran group and the reference comparator (patisiran) group as of the data cutoff date (10 November 2020).	9.5% 4/42 • Non-serious AEs from first dose of study drug through Month 9. SAEs from signing of informed consent through Month 9. Adverse events are provided for the vutrisiran group and the reference comparator (patisiran) group as of the data cutoff date (10 November 2020).
Injury, poisoning and procedural complications Ligament sprain	2.5% 3/122 • Non-serious AEs from first dose of study drug through Month 9. SAEs from signing of informed consent through Month 9. Adverse events are provided for the vutrisiran group and the reference comparator (patisiran) group as of the data cutoff date (10 November 2020).	7.1% 3/42 • Non-serious AEs from first dose of study drug through Month 9. SAEs from signing of informed consent through Month 9. Adverse events are provided for the vutrisiran group and the reference comparator (patisiran) group as of the data cutoff date (10 November 2020).
Investigations Alanine aminotransferase increased	0.82% 1/122 • Non-serious AEs from first dose of study drug through Month 9. SAEs from signing of informed consent through Month 9. Adverse events are provided for the vutrisiran group and the reference comparator (patisiran) group as of the data cutoff date (10 November 2020).	7.1% 3/42 • Non-serious AEs from first dose of study drug through Month 9. SAEs from signing of informed consent through Month 9. Adverse events are provided for the vutrisiran group and the reference comparator (patisiran) group as of the data cutoff date (10 November 2020).
Investigations Aspartate aminotransferase increased	0.82% 1/122 • Non-serious AEs from first dose of study drug through Month 9. SAEs from signing of informed consent through Month 9. Adverse events are provided for the vutrisiran group and the reference comparator (patisiran) group as of the data cutoff date (10 November 2020).	7.1% 3/42 • Non-serious AEs from first dose of study drug through Month 9. SAEs from signing of informed consent through Month 9. Adverse events are provided for the vutrisiran group and the reference comparator (patisiran) group as of the data cutoff date (10 November 2020).
Investigations Vitamin A decreased	6.6% 8/122 • Non-serious AEs from first dose of study drug through Month 9. SAEs from signing of informed consent through Month 9. Adverse events are provided for the vutrisiran group and the reference comparator (patisiran) group as of the data cutoff date (10 November 2020).	4.8% 2/42 • Non-serious AEs from first dose of study drug through Month 9. SAEs from signing of informed consent through Month 9. Adverse events are provided for the vutrisiran group and the reference comparator (patisiran) group as of the data cutoff date (10 November 2020).
Musculoskeletal and connective tissue disorders Arthralgia	9.0% 11/122 • Non-serious AEs from first dose of study drug through Month 9. SAEs from signing of informed consent through Month 9. Adverse events are provided for the vutrisiran group and the reference comparator (patisiran) group as of the data cutoff date (10 November 2020).	9.5% 4/42 • Non-serious AEs from first dose of study drug through Month 9. SAEs from signing of informed consent through Month 9. Adverse events are provided for the vutrisiran group and the reference comparator (patisiran) group as of the data cutoff date (10 November 2020).
Musculoskeletal and connective tissue disorders Back pain	4.1% 5/122 • Non-serious AEs from first dose of study drug through Month 9. SAEs from signing of informed consent through Month 9. Adverse events are provided for the vutrisiran group and the reference comparator (patisiran) group as of the data cutoff date (10 November 2020).	7.1% 3/42 • Non-serious AEs from first dose of study drug through Month 9. SAEs from signing of informed consent through Month 9. Adverse events are provided for the vutrisiran group and the reference comparator (patisiran) group as of the data cutoff date (10 November 2020).
Musculoskeletal and connective tissue disorders Pain in extremity	11.5% 14/122 • Non-serious AEs from first dose of study drug through Month 9. SAEs from signing of informed consent through Month 9. Adverse events are provided for the vutrisiran group and the reference comparator (patisiran) group as of the data cutoff date (10 November 2020).	9.5% 4/42 • Non-serious AEs from first dose of study drug through Month 9. SAEs from signing of informed consent through Month 9. Adverse events are provided for the vutrisiran group and the reference comparator (patisiran) group as of the data cutoff date (10 November 2020).
Nervous system disorders Dizziness	7.4% 9/122 • Non-serious AEs from first dose of study drug through Month 9. SAEs from signing of informed consent through Month 9. Adverse events are provided for the vutrisiran group and the reference comparator (patisiran) group as of the data cutoff date (10 November 2020).	0.00% 0/42 • Non-serious AEs from first dose of study drug through Month 9. SAEs from signing of informed consent through Month 9. Adverse events are provided for the vutrisiran group and the reference comparator (patisiran) group as of the data cutoff date (10 November 2020).
Nervous system disorders Headache	6.6% 8/122 • Non-serious AEs from first dose of study drug through Month 9. SAEs from signing of informed consent through Month 9. Adverse events are provided for the vutrisiran group and the reference comparator (patisiran) group as of the data cutoff date (10 November 2020).	11.9% 5/42 • Non-serious AEs from first dose of study drug through Month 9. SAEs from signing of informed consent through Month 9. Adverse events are provided for the vutrisiran group and the reference comparator (patisiran) group as of the data cutoff date (10 November 2020).
Nervous system disorders Neuralgia	4.9% 6/122 • Non-serious AEs from first dose of study drug through Month 9. SAEs from signing of informed consent through Month 9. Adverse events are provided for the vutrisiran group and the reference comparator (patisiran) group as of the data cutoff date (10 November 2020).	7.1% 3/42 • Non-serious AEs from first dose of study drug through Month 9. SAEs from signing of informed consent through Month 9. Adverse events are provided for the vutrisiran group and the reference comparator (patisiran) group as of the data cutoff date (10 November 2020).
Skin and subcutaneous tissue disorders Rash	5.7% 7/122 • Non-serious AEs from first dose of study drug through Month 9. SAEs from signing of informed consent through Month 9. Adverse events are provided for the vutrisiran group and the reference comparator (patisiran) group as of the data cutoff date (10 November 2020).	0.00% 0/42 • Non-serious AEs from first dose of study drug through Month 9. SAEs from signing of informed consent through Month 9. Adverse events are provided for the vutrisiran group and the reference comparator (patisiran) group as of the data cutoff date (10 November 2020).