Vutrisiran: Post-Hoc Analysis of the HELIOS-B Monotherapy Population with Observations Following Tafamidis Initiation Censored

Vutrisiran: Post-Hoc Analysis of the HELIOS-B Monotherapy Population with Observations Following Tafamidis Initiation Censored

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 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. After the double-blind period, all remaining eligible patients were allowed to receive vutrisiran in an OLE.1

Endpoints were prespecified for assessment in both the overall population and the monotherapy population (patients not receiving tafamidis at baseline). 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.1

A total of 395 patients were not on tafamidis at baseline and comprised the monotherapy population. Patients that were not receiving tafamidis at baseline could initiate tafamidis at the discretion of the investigator. In the monotherapy population, a total of 21.5% of patients initiated tafamidis after randomization in a median (IQR) of 18 (12-28 months), which included 44 out of 196 patients (22%) in the vutrisiran group and 41 out of 199 patients (21%) in the placebo group.1,2  

Post-Hoc Analysis

A post-hoc analysis of data from the monotherapy population with observations after tafamidis initiation censored was conducted to further assess the monotherapy population in the HELIOS-B study.2

 Efficacy Results

Primary Endpoint: Composite of All-Cause Mortality and Recurrent CV Events Through the Double‑Blind Period

With censoring of observations after tafamidis initiation in the monotherapy population, treatment with vutrisiran compared with placebo resulted in a HR of 0.68 (95% CI 0.49, 0.95) in the composite of all-cause mortality and recurrent CV events (Figure 1). The reduction in risk of the composite of all‑cause mortality and recurrent events was consistent with the result observed from the primary analysis without censoring (HR 0.67, 95% CI 0.49, 0.93; P=0.02).2

Figure 1. All-Cause Mortality and Recurrent CV Events in the Monotherapy Population With and Without Censoring of Observations After Tafamidis Initiation.2

Secondary Endpoints

A summary of the secondary endpoints assessed in the monotherapy population with and without censoring of observations after tafamidis initiation are presented in Table 1.2

Table 1. Secondary Endpoints Assessed in the Monotherapy Population.2

 Safety Results

A summary of the safety results observed during the double-blind period in the monotherapy population with and without censoring of observations after tafamidis initiation are presented in Table 2.2

Table 2. Safety Results in the Monotherapy Population During the Double-Blind Period.2

 Abbreviations

6-MWT = 6-minute walk test; AE = adverse event; ATTR = transthyretin amyloidosis; ATTR-CM = transthyretin amyloidosis with cardiomyopathy; CI = confidence interval; CV = cardiovascular; hATTR = hereditary transthyretin amyloidosis; HR = hazard ratio; IQR = interquartile range; KCCQ‑OS = Kansas City Cardiomyopathy Questionnaire‑Overall Summary; LS = least squares; NT-proBNP = N-terminal pro‑B‑type natriuretic peptide; NYHA = New York Heart Association; OLE = open-label extension; SAE = serious adverse event; wtATTR = wild-type transthyretin amyloidosis.

Updated 30 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.  Witteles R, Kristen A, Habib G, et al. Outcomes of the HELIOS-B monotherapy population: a post hoc analysis censoring data following tafamidis initiation. Presented at: Heart Failure Society of America (HFSA) Annual Scientific Meeting; September 26-29, 2025; Minneapolis, MN, USA.