Alnylam Pharmaceuticals (ALNY) Study Result summary

Study background and design

• HELIOS-B was a Phase III, randomized, double-blind, placebo-controlled global study evaluating vutrisiran, an RNAi therapeutic, in 655 patients with ATTR amyloidosis with cardiomyopathy, including both wild-type and hereditary forms.

• Patients were randomized 1:1 to receive vutrisiran 25mg or placebo every three months for up to 36 months; 40% were on tafamidis at baseline.

• The primary endpoint was a composite of all-cause mortality and recurrent cardiovascular events, assessed in both overall and monotherapy (no tafamidis at baseline) populations.

• Secondary endpoints included 6-minute walk test, Kansas City Cardiomyopathy Questionnaire (KCCQ), all-cause mortality (up to 42 months), and NYHA class.

• After the double-blind period, eligible patients could receive vutrisiran in an open-label extension.

Key efficacy results

• Vutrisiran achieved statistical significance on all 10 pre-specified endpoints in both overall and monotherapy populations, including the primary endpoint (HR 0.718, 28% reduction, p=0.0118 overall; HR 0.672, 33% reduction, p=0.0162 monotherapy).

• Significant improvements were seen in 6-minute walk test, KCCQ, and NYHA class at 30 months in both populations (p<0.025 for all).

• All-cause mortality was reduced by 36% in the overall population (HR 0.645, p<0.025) and 35% in monotherapy (HR 0.655, p<0.05) up to Month 42.

• Benefits were consistent across all key subgroups, including those on background tafamidis, wild-type and hereditary disease, and varying disease severity.

• Results support potential for vutrisiran to become a new standard of care for ATTR-CM.

Safety and tolerability

• Vutrisiran demonstrated a safety and tolerability profile consistent with previous experience; adverse events, serious adverse events, and discontinuations were similar between vutrisiran and placebo arms.

• No adverse events occurred more than 3% more frequently in the vutrisiran arm compared to placebo.

• Vutrisiran treatment leads to decreased serum vitamin A levels; supplementation at the recommended daily allowance is advised.

• Most common adverse reactions in prior studies included arthralgia (11%), dyspnea (7%), and decreased vitamin A (7%).