Alnylam Pharmaceuticals, Inc. announced positive topline results from its HELIOS-B Phase 3 study of vutrisiran, an investigational RNAi therapeutic in development for the treatment of ATTR amyloidosis with cardiomyopathy (ATTR-CM). The study met the primary endpoint, demonstrating a statistically significant reduction in the composite of all-cause mortality and recurrent cardiovascular events during the double-blind period in both the overall population (HR 0.718, p-value 0.0118; n=654) and in the monotherapy population (patients not receiving tafamidis at baseline; HR 0.672, p-value 0.0162; n=395). The study also demonstrated statistically significant improvements across all secondary endpoints in both the overall and monotherapy populations.

This includes key measures of disease progression: 6-minute walk test (6-MWT), Kansas City Cardiomyopathy Questionnaire (KCCQ) and New York Heart Association (NYHA) Class at Month 30 (p<0.025 for all). Importantly, treatment with vutrisiran also reduced all-cause mortality in the overall population (HR 0.645, p<0.025) and in the monotherapy population (HR 0.655, p<0.05) up to Month 42. This was a pre-specified, intent-to-treat analysis that included up to six months of data from the open-label extension.

In addition, vutrisiran demonstrated consistent effects on the primary composite endpoint and all secondary endpoints across all key subgroups, including baseline tafamidis use, ATTR disease type and measures of disease severity. In the HELIOS-B study, vutrisiran demonstrated encouraging safety and tolerability, consistent with its established profile. Rates of adverse events (AEs), serious AEs and AEs leading to study drug discontinuation were similar between the vutrisiran and placebo arms. No AEs were seen =3% more frequently in the vutrisiran arm compared to the placebo arm.

HELIOS-B is a Phase 3, randomized, double-blind, placebo-controlled multicenter global study designed and powered to evaluate the efficacy and safety of vutrisiran on the reduction of all-cause mortality and recurrent cardiovascular events as a primary composite endpoint in patients with ATTR amyloidosis with cardiomyopathy in the overall and monotherapy populations. The study randomized 655 adult patients with ATTR amyloidosis (hereditary or wild-type) with cardiomyopathy. Patients were randomized 1:1 to receive vutrisiran 25mg or placebo subcutaneously once every three months during a double-blind treatment period of up to 36 months.

After the double-blind period, all eligible patients remaining on the study may receive vutrisiran in an open-label extension period. Detailed results from the HELIOS-B study have been submitted as a late-breaking abstract to the European Society of Cardiology for presentation. The Company plans to proceed with global regulatory submissions starting later this year, including filing a supplemental New Drug Application with the U.S. Food and Drug Administration using a Priority Review Voucher.