Vutrisiran: Ocular Adverse Events

Vutrisiran: Ocular Adverse Events

The following information is provided in response to your unsolicited inquiry. It is intended to provide you with a review of the available scientific literature and to assist you in forming your own conclusions in order to make healthcare decisions. This document is not for further dissemination or publication without authorization.

The full Prescribing Information for AMVUTTRA® (vutrisiran) is provided here. Alnylam Pharmaceuticals does not recommend the use of its products in any manner that is inconsistent with the approved Prescribing Information. This resource may contain information that is not in the approved Prescribing Information.

If you are seeking additional scientific information related to Alnylam medicines, you may visit the Alnylam US Medical Affairs website at RNAiScience.com.

 Summary

Index

Clinical Data – Global Safety Database – Label Information – Abbreviations – References

 Clinical Data

HELIOS-A Study

HELIOS-A was a phase 3, global, randomized, open-label study designed to evaluate the efficacy and safety of vutrisiran in patients with hATTR-PN. Patients were randomized (3:1) to receive either vutrisiran 25 mg every 3 months by subcutaneous injection (n=122) or patisiran 0.3 mg/kg every 3 weeks by IV infusion (as a reference group, n=42) for 18 months. This study used the placebo arm of the APOLLO study as an external control arm (n=77) for the primary endpoint and most other efficacy endpoints. The primary endpoint was the change from baseline in mNIS+7 at 9 months. After the 18‑month treatment period, all remaining eligible patients were eligible to receive vutrisiran in the RTE.4

During the 18-month treatment period, ocular AEs were reported in 35 patients (28.7%) in the vutrisiran group and 20 patients (20.6%) in the APOLLO-placebo group.5

HELIOS-B

HELIOS-B was a phase 3, global, randomized, double-blind, placebo-controlled, multicenter study designed to evaluate the efficacy and safety of vutrisiran in patients with ATTR-CM, including both hATTR and wtATTR. Patients were randomized (1:1) to receive either vutrisiran 25 mg (n=326) or placebo (n=329) every 3 months by subcutaneous injection for up to 36 months. The primary endpoint was the composite endpoint of all-cause mortality and recurrent CV events (CV hospitalizations and urgent heart failure visits) at the end of the double-blind period in the overall population and in the monotherapy population (patients not receiving tafamidis at baseline). After the double-blind period, all remaining eligible patients were allowed to receive vutrisiran in an OLE.6

During the double-blind treatment period, ocular AEs were reported in 47 patients (14.4%) in the vutrisiran group and 66 patients (20.1%) in the placebo group.5  

Pooled Safety Analysis of HELIOS-A and HELIOS-B

A pooled analysis of AEs in HELIOS-A and HELIOS-B, including data from 707 patients who received at least one dose of vutrisiran at any time during the studies, was conducted to evaluate the safety of vutrisiran in patients with ATTR who received treatment for up to 58 months.1

The HELIOS-A vutrisiran group consisted of 160 patients who received at least one dose of vutrisiran in the initial 18-month treatment period (n=122) or initially received patisiran in the treatment period and were re-randomized to receive vutrisiran during the RTE (n=38). The HELIOS-B vutrisiran group consisted of 547 patients who received at least one dose of vutrisiran during the double-blind treatment period (n=326) or initially received placebo during the double-blind period and transitioned to vutrisiran in the OLE (n=221).1  

Ocular AEs by SOC were evaluated in the analysis (Table 1). In the combined vutrisiran group, ocular AEs were reported in 106 out of 707 patients (15.0%; 1518.9 PY; AER: 11.3 per 100 PY). The most common ocular AEs occurring in >2% of patients treated with vutrisiran were cataract (2.7%) and dry eye (2.1%).1

Table 1. Ocular Adverse Events.1,5

Ocular AEs reported in patients who received vutrisiran for up to 58 months in the pooled analysis were consistent with those reported for patients who received vutrisiran during the randomized periods of HELIOS-A and HELIOS-B.1

Pooled Safety Analysis of Ocular Adverse Events from Vutrisiran and Patisiran Clinical Studies

An analysis of pooled data from patients with ATTR-CM or hATTR-PN who received at least 1 dose of vutrisiran, patisiran, or placebo from Phase 3 studies was conducted to evaluate the frequency and event rates of clinical and/or laboratory AEs related to vitamin A deficiency and visual impairment and blindness (excluding color blindness). The event rates for AEs categorized under the HLT “Visual impairment and blindness” are presented in Table 1.2

Table 1. Event Rates for AEs Categorized as “Visual Impairment and Blindness”.2

AEs related to Vitamin A deficiency from vutrisiran clinical studies are presented in Table 2. There were no reports of visual AEs directly attributed to vitamin A deficiency and therefore were no confirmed cases of clinical vitamin A deficiency. No events attributed to vitamin A deficiency led to study drug discontinuation.2

Table 2. Event Rates for AEs Related to Vitamin A Deficiency.2

 Global Safety Database

A cumulative post-marketing review of Alnylam Pharmaceuticals’ global safety database did not identify any safety concerns involving ocular AEs related to vutrisiran.3

 Amvuttra Prescribing Information - Relevant content

For relevant labeling information, please refer to the following sections of the AMVUTTRA Prescribing Information7:

      WARNINGS AND PRECAUTIONS Section 5.1 Reduced Serum Vitamin A Levels and Recommended Supplementation

      PATIENT COUNSELING INFORMATION Section 17 Recommended Vitamin A Supplementation

 Abbreviations

AE = adverse event; AER  = adverse event rate; ATTR = transthyretin amyloidosis; ATTR-CM = transthyretin amyloidosis with cardiomyopathy; CV = cardiovascular; EAER = exposure-adjusted event rate; hATTR = hereditary transthyretin amyloidosis; hATTR-PN = hereditary transthyretin amyloidosis with polyneuropathy; HLT = high-level term; IV = intravenous; mNIS+7 = modified Neuropathy Impairment Score +7; OLE = open-label extension; PT = preferred term; PY = patient-years; RTE = randomized treatment extension; SOC = system organ class; wtATTR = wild-type transthyretin amyloidosis.

Updated 20 May 2026

References

1.  Witteles RM, Garcia-Pavia P, Morbach C, et al. Vutrisiran in transthyretin amyloidosis: a pooled safety analysis of HELIOS-A and HELIOS-B. JACC Adv. 2025;4(9). doi:10.1016/j.jacadv.2025.102066

2.  Blaner W, Whelan C, González-Costello J, et al. Treatment with transthyretin-lowering RNA interference therapeutics is not associated with ocular or other clinical events due to vitamin A reduction: Pooled analysis of vutrisiran and patisiran data. Presented at: Heart Failure Association (HFA); May 9-12, 2026; Barcelona, Spain.

3.  Alnylam Pharmaceuticals. Data on file. MED-ALL-VUTRI-2600002.

4.  Adams D, Tournev IL, Taylor MS, et al. Efficacy and safety of vutrisiran for patients with hereditary transthyretin-mediated amyloidosis with polyneuropathy: a randomized clinical trial. Amyloid. 2023;30(1):18-26. doi:10.1080/13506129.2022.2091985

5.  Supplement to: Witteles RM, Garcia-Pavia P, Morbach C, et al. Vutrisiran in transthyretin amyloidosis: a pooled safety analysis of HELIOS-A and HELIOS-B. JACC Adv. 2025;4(9). doi:10.1016/j.jacadv.2025.102066

6.  Fontana M, Berk JL, Gillmore JD, et al. Vutrisiran in patients with transthyretin amyloidosis with cardiomyopathy. N Engl J Med. 2025;392(1):33-44. doi:10.1056/NEJMoa2409134

7.  AMVUTTRA (vutrisiran) Prescribing Information. Cambridge, MA: Alnylam Pharmaceuticals, Inc.