Alnylam Pharmaceuticals (ALNY) Study Result summary

Study background and design

• HELIOS-B was a Phase 3, randomized, double-blind, placebo-controlled global trial evaluating vutrisiran in 655 patients with ATTR amyloidosis with cardiomyopathy, including both wild-type and hereditary forms.

• Patients were randomized 1:1 to receive vutrisiran 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 up to 36 months; secondary endpoints included 6-minute walk test, 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.

• Detailed results have been submitted for presentation at the European Society of Cardiology, with global regulatory submissions planned.

Key efficacy results

• Vutrisiran achieved statistical significance on all 10 pre-specified endpoints in both overall and monotherapy populations.

• In the overall population, the hazard ratio for the primary endpoint was 0.718 (28% risk reduction, p=0.0118); in monotherapy, 0.672 (33% risk reduction, p=0.0162).

• All-cause mortality was reduced by 36% in the overall population and 35% in monotherapy, both statistically significant.

• Statistically significant improvements were seen in 6-minute walk test, KCCQ, NYHA class, and all secondary endpoints.

• Benefits were consistent across all key subgroups, including those on background tafamidis, ATTR type, and disease severity, with evidence of additive effects.

Safety and tolerability

• Vutrisiran demonstrated a favorable safety and tolerability profile, with similar rates of adverse events, serious adverse events, and discontinuations compared to placebo.

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

• 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%).