Vutrisiran: Safety Results from HELIOS-B

Vutrisiran: Safety Results from HELIOS-B

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

Abbreviations

AE = adverse event; ARR = adjusted rate ratio; ATTR = transthyretin amyloidosis; ATTR-CM = transthyretin amyloidosis with cardiomyopathy; CI = confidence interval; CV = cardiovascular; ER = event rate; GI = gastrointestinal; hATTR = hereditary transthyretin amyloidosis; MedDRA = Medical Dictionary for Regulatory Activities; NT‑proBNP = N‑terminal prohormone of B‑type natriuretic peptide; NYHA = New York Heart Association; OLE = open-label extension; PY = patient-years; RR = rate ratio; SAE = serious adverse event; SOC = system organ class; wtATTR = wild-type transthyretin amyloidosis.

 Index

Safety Results in HELIOS-B – Post Hoc Safety Analysis –References

 Safety Results in 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 treatment period in the overall population and in the monotherapy population (patients not receiving tafamidis at baseline). After the double-blind treatment period, all eligible patients remaining on the study were allowed to receive vutrisiran in an OLE.1

Safety Results

In the overall population, the incidence of AEs was similar between the two groups, with 322 patients (99%) and 323 patients (98%) reporting at least one AE in the vutrisiran and placebo groups, respectively. A summary of the safety results during the double-blind period are presented in Table 1. There were no clinically relevant changes in laboratory measures (including hematologic measures, blood chemistry values, liver function tests, and renal function tests), vital signs, or electrocardiograms observed in either treatment group.1,3

Table 1. Safety Summary in the Overall Population During the Double-Blind Period.3

Post-Hoc Safety Analysis

A post-hoc safety analysis was conducted to compare event rates for overall and SOC-specific AEs observed in the vutrisiran and placebo groups from HELIOS-B.2

In the overall population, the rate of overall AEs was 428 events per 100 PY in the vutrisiran group and 559 events per 100 PY in the placebo group, resulting in a RR (vutrisiran/placebo) of 0.77. The mean cumulative adverse events per patient in the overall population were observed to be lower in the vutrisiran group than placebo, with an ARR (vutrisiran/placebo) of 0.75 (Figure 1).2

Figure 1. Mean Cumulative Events Per Patient During the Double-Blind Period.2

The rates of AEs by the top 10 SOCs, identified by those with the highest number of AEs observed during the double-blind period, are presented in Table 2.2

Table 2. AE Rates by SOC in the Overall Population.2,a

References

1.  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

2.  Schwarting SK, Tsujita K, Sperry BW, et al. Fewer adverse events reported in ATTR-CM patients treated with vutrisiran versus placebo: Post hoc safety analysis from HELIOS-B. Presented at: European Society of Cardiology (ESC) Congress; August 28-31, 2026; Munich, Germany.

3.  Supplement to: 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

Updated 11 September 2026