CAMBRIDGE, Mass. — Alnylam Pharmaceuticals has presented compelling new findings from its Phase 3 HELIOS-B study of AMVUTTRA® (vutrisiran), showing that the RNAi therapeutic significantly reduces mortality and cardiovascular (CV) events in patients with transthyretin-mediated amyloidosis with cardiomyopathy (ATTR-CM). The updated data were unveiled at the Heart Failure 2025 Congress, organized by the European Society of Cardiology, and simultaneously published in JACC.
The analysis demonstrated that vutrisiran, which rapidly reduces levels of transthyretin (TTR), led to a 46% reduction in urgent heart failure visits during the double-blind period, compared with placebo. Additionally, it reduced the risk of all-cause mortality by 36% and cardiovascular mortality by 33% over a 42-month follow-up period. These findings reinforce the therapy’s potential as a disease-modifying treatment for patients with ATTR-CM.
The HELIOS-B trial included 654 patients with ATTR-CM, all receiving background therapies including TTR stabilizers and SGLT2 inhibitors. Vital status was tracked for over 99% of participants through 42 months, strengthening the reliability of the results.
In addition to mortality benefits, vutrisiran showed significant reductions in other key cardiovascular endpoints. The therapy reduced heart failure hospitalizations by 33%, CV events by 27%, and CV-related hospitalizations by 25% through 36 months.
“These new data—including the impact on mortality, cardiovascular events, and the marked reduction in urgent heart failure visits—continue to underscore the consistency and magnitude of benefit we’re seeing with AMVUTTRA,” said Dr. Pushkal Garg, Chief Medical Officer at Alnylam. “Given the substantial use of standard heart failure treatments in this population, these results reinforce vutrisiran as a clinically differentiated, first-line treatment option for patients with ATTR-CM.”
In a separate session at the same congress, Alnylam will present results from a subgroup analysis of HELIOS-B, examining outcomes for patients who experienced disease progression while on tafamidis. These findings are expected to offer insights into vutrisiran’s benefits in more advanced cases of ATTR-CM.
Alnylam also announced the upcoming TRITON-CM Phase 3 trial of nucresiran, its next-generation RNAi therapeutic targeting TTR. Nucresiran, which has demonstrated over 95% TTR knockdown with just twice-annual dosing in Phase 1, will be tested in an event-driven outcomes trial involving around 1,200 patients with either wild-type or variant ATTR-CM. The trial is expected to begin in the first half of 2025.
Vutrisiran has already received FDA and ANVISA approval for treating cardiomyopathy caused by ATTR amyloidosis. In Europe, the Committee for Medicinal Products for Human Use (CHMP) has issued a positive opinion recommending approval, with a formal decision expected by the third quarter of 2025. Regulatory reviews are also underway in Japan, and Alnylam plans further global submissions throughout the year.
