Vutrisiran: HELIOS-B OLE

Vutrisiran: HELIOS-B OLE

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

Study Design – Efficacy Results – Safety Results – Abbreviations – References

 Study Design

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).1

After the double-blind period, all remaining eligible patients were allowed to receive vutrisiran in an OLE for up to 24 months (Figure 1). Of the 478 patients who completed the double-blind period, 466 patients (97%) entered the OLE. As of the data cutoff for Month 12 of the OLE, 213 patients who initially received vutrisiran and 189 patients who initially received placebo in the double-blind period have continued treatment.2

Figure 1. HELIOS-B Double-Blind Period and OLE Study Design.2

 Efficacy Results

Composite of All-Cause Mortality and Recurrent CV Events

Treatment with vutrisiran compared with placebo reduced the risk in time to first CV event or all-cause mortality through Month 48 (Month 12 of the OLE) by 37% in the overall population (time-to-first: HR = 0.631, 95% CI: 0.506, 0.788; P=0.0001) and 42% in the monotherapy population (time-to-first: HR =  0.577, 95% CI: 0.436, 0.762; P=0.0002) (Figure 2).2

Figure 2. Time to First CV Event or All-Cause Mortality Through Month 12 of the OLE.2,a  

All-Cause Mortality

Treatment with vutrisiran compared with placebo reduced the risk of all-cause mortality through Month 48 (Month 12 of the OLE) by 37% in the overall population (time-to-event: HR = 0.626, 95% CI: 0.464, 0.843; P=0.0023) and 39% in the monotherapy population (time-to-event: HR = 0.607, 95% CI: 0.426, 0.866; P=0.0070) (Figure 3).2

Figure 3. Time to All-Cause Mortality Through Month 12 of the OLE.2,a

KCCQ-OS

The changes from baseline in KCCQ-OS at Month 12 of the OLE in the overall and monotherapy populations are summarized in Table 1. The median (95% CI) changes from baseline in KCCQ-OS in the overall and monotherapy populations are presented in Figure 4.2

Table 1. Change from Baseline in KCCQ-OS at Month 12 of the OLE.2

Figure 4. Median Change from Baseline in KCCQ-OS Through Month 12 of the OLE.2

NYHA Class

The proportion of patients with stable or improved NYHA class from baseline at Month 12 of the OLE are summarized in Table 2.2

Table 2. Proportion of Patients with Stable or Improved NYHA Class from Baseline at Month 12 of the OLE.2

Cardiac Biomarkers

NT-proBNP

Treatment with vutrisiran compared with placebo resulted in an adjusted geometric mean fold-change ratio of 0.66 (95% CI: 0.58, 0.74) and 0.55 (95% CI: 0.47, 0.64) for NT-proBNP from baseline to Month 12 of the OLE in the overall and monotherapy populations, respectively (Figures 5 and 6).2

Troponin I

Treatment with vutrisiran compared with placebo resulted in an adjusted geometric mean fold-change ratio of 0.71 (95% CI: 0.64, 0.79) and 0.57 (95% CI: 0.49, 0.65) for troponin I from baseline to Month 12 of the OLE in the overall and monotherapy populations, respectively (Figures 5 and 6).2

Figure 5. NT-proBNP and Troponin I Through Month 12 of the OLE in the Overall Population.2

Figure 6. NT-proBNP and Troponin I Through Month 12 of the OLE in the Monotherapy Population.2

 Safety Results

The median exposure to vutrisiran was 47.5 months (range 0.6-60.5) for the vutrisiran/vutrisiran group and 13.7 months (range 0.6-22.1) for the placebo/vutrisiran group. The exposure-adjusted event rates per 100 PY of the placebo/vutrisiran and vutrisiran/vutrisiran groups are summarized in Table 3.2

The safety data for long-term treatment with vutrisiran through Month 12 of the OLE were consistent with those reported for the double-blind period. The rates of AEs did not increase with longer treatment. Higher event rates for SAEs and severe AEs in the placebo/vutrisiran group compared with the vutrisiran/vutrisiran group were consistent with more advanced disease following placebo treatment during the double-blind period.2

Table 3. Safety Results During the Vutrisiran Exposure Period.2,a

 Abbreviations

6-MWT = 6-minute walk test; ACM = all-cause mortality; AE = adverse event; ATTR = transthyretin amyloidosis; ATTR‑CM = transthyretin amyloidosis with cardiomyopathy; BL = baseline; CI = confidence interval; CV = cardiovascular; D = day; DB = double-blind; hATTR = hereditary transthyretin amyloidosis; HF = heart failure; HR = hazard ratio; KCCQ-OS = Kansas City Cardiomyopathy Questionnaire-Overall Summary; LS = least squares; LSMD = least squares mean difference; M = month; MMRM = mixed models with repeated measures; NT-proBNP = N-terminal prohormone of B-type natriuretic peptide; NYHA = New York Heart Association; OLE = open-label extension; OR = odds ratio; PND = polyneuropathy disability; PY = patient-years; q3M = every 3 months; SAE = serious adverse event; SC = subcutaneous; SEM = standard error of the mean; TTR = transthyretin; wtATTR = wild-type transthyretin amyloidosis.  

Updated 03 September 2025

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.  Garcia-Pavia P, Witteles R, Morbach C, et al. HELIOS-B: 12-month results from the open-label extension period of vutrisiran in patients with transthyretin amyloidosis with cardiomyopathy. Presented at: European Society of Cardiology (ESC); August 29-September 1, 2025; Madrid, Spain.