Alnylam Pharmaceuticals (ALNY) Study Result summary

Study background and design

• HELIOS-B was a Phase 3, randomized, double-blind, placebo-controlled trial in 655 adults with ATTR amyloidosis with cardiomyopathy, including both wild-type and hereditary/variant forms, with 40% on background tafamidis at baseline and substantial use of SGLT2 inhibitors and diuretics.

• Patients were stratified by tafamidis use, ATTR disease type, NYHA class, and age, and randomized 1:1 to receive vutrisiran 25mg or placebo subcutaneously every three months for 33–36 months, followed by an open-label extension.

• The study population reflected contemporary clinical practice, with many patients in NYHA Class I or II and on effective background therapies.

Efficacy results

• Vutrisiran met all primary and secondary endpoints, reducing the composite of all-cause mortality and recurrent cardiovascular events by 28% (HR=0.718, p=0.0118) in the overall population, with a 31% reduction in all-cause mortality during the double-blind period and 36% up to 42 months.

• In the monotherapy subgroup (no baseline tafamidis), vutrisiran reduced the composite endpoint by 33% (HR=0.672, p=0.0162) and all-cause mortality by 35%.

• Benefits were observed in both monotherapy and combination with tafamidis, with evidence of additive efficacy and favorable trends in patients on baseline tafamidis.

• Subgroup analyses showed consistent efficacy across age, disease type, NYHA class, and NT-proBNP, with greater benefit in patients with earlier disease (age <75, NT-proBNP ≤2000), including up to 65% reduction in all-cause mortality in certain subgroups.

Functional and quality of life outcomes

• Vutrisiran stabilized or improved functional capacity (six-minute walk test), health status (KCCQ), and NYHA class over 30 months, with greater magnitude of improvement than typically seen in heart failure trials.

• NT-proBNP, a key biomarker, showed significantly less increase or a 32% relative reduction at Month 30 in the overall population and 43% in the monotherapy subgroup, indicating stabilization of cardiac function.