Alnylam's Vutrisiran Phase 3 HELIOS-B Study Shows Positive Results

Alnylam Pharmaceuticals, Inc. has announced successful results from its HELIOS-B Phase 3 study of vutrisiran, an investigational RNAi therapeutic for the treatment of ATTR amyloidosis with cardiomyopathy (ATTR-CM). The study achieved its primary endpoint by demonstrating a significant reduction in the composite of all-cause mortality and recurrent cardiovascular events during the double-blind period. The reductions were observed in both the overall population (HR 0.718, p=0.0118) and the monotherapy population—patients not receiving tafamidis at baseline (HR 0.672, p=0.0162).

The study also showed statistically significant improvements in all secondary endpoints, including key measures of disease progression: the 6-minute walk test (6-MWT), the Kansas City Cardiomyopathy Questionnaire (KCCQ), and the New York Heart Association (NYHA) Class at Month 30. Notably, treatment with vutrisiran reduced all-cause mortality by 36% in the overall population (HR 0.645, p<0.025) and by 35% in the monotherapy population (HR 0.655, p<0.05) up to Month 42. This analysis was pre-specified and included up to six months of data from the open-label extension.

Pushkal Garg, M.D., Chief Medical Officer of Alnylam, expressed enthusiasm about the data, indicating that vutrisiran has the potential to address the needs of patients with ATTR amyloidosis with cardiomyopathy, a progressively debilitating and ultimately fatal disease. The results suggest that vutrisiran improved cardiovascular outcomes, survival, function, and quality of life in all patient groups with ATTR cardiomyopathy.

Vutrisiran demonstrated consistent effects on both the primary composite endpoint and all secondary endpoints across all key subgroups, including those using baseline tafamidis, different ATTR disease types, and varying measures of disease severity. Safety and tolerability of vutrisiran were encouraging and consistent with its established profile, with adverse events (AEs), serious AEs, and AEs leading to discontinuation of the study drug being similar between the vutrisiran and placebo groups.

Yvonne Greenstreet, MBChB, Chief Executive Officer of Alnylam, highlighted that the HELIOS-B study results suggest vutrisiran’s potential as a transformative medicine for patients with ATTR amyloidosis with cardiomyopathy. Assuming favorable regulatory review, vutrisiran could become the new standard of care for treating this disease, driving Alnylam’s next phase of significant growth.

HELIOS-B (NCT: NCT04153149) is a Phase 3, randomized, double-blind, placebo-controlled multicenter global study designed to evaluate the efficacy and safety of vutrisiran on reducing all-cause mortality and recurrent cardiovascular events in patients with ATTR amyloidosis with cardiomyopathy. The study involved 655 adult patients with ATTR amyloidosis (hereditary or wild-type) with cardiomyopathy, who were randomized to receive vutrisiran 25mg or placebo subcutaneously every three months during a double-blind treatment period of up to 36 months. Following the double-blind period, eligible patients could continue receiving vutrisiran in an open-label extension.

Detailed results from the HELIOS-B study have been submitted as a late-breaking abstract to the European Society of Cardiology. Alnylam plans to proceed with global regulatory submissions later this year, including filing a supplemental New Drug Application with the U.S. Food and Drug Administration using a Priority Review Voucher.

Transthyretin amyloidosis (ATTR) is a rapidly progressive, debilitating, and fatal disease caused by misfolded transthyretin (TTR) proteins that accumulate as amyloid deposits in various parts of the body, including nerves, the heart, and the gastrointestinal tract. The disease manifests as polyneuropathy, cardiomyopathy, or both. There are two forms of ATTR: hereditary ATTR (hATTR), caused by a TTR gene variant, and wild-type ATTR (wtATTR), which occurs without a TTR gene variant.

AMVUTTRA® (vutrisiran) is an RNAi therapeutic that targets mutant and wild-type transthyretin (TTR), addressing the underlying cause of transthyretin amyloidosis. Administered quarterly via subcutaneous injection, AMVUTTRA is approved in over 15 countries for the treatment of hereditary transthyretin-mediated amyloidosis (hATTR-PN) in adults and is in development for treating ATTR amyloidosis with cardiomyopathy (ATTR-CM).