Additional Data from HELIOS-B

Alnylam Pharmaceuticals, Inc. (Nasdaq: ALNY), the leading RNAi therapeutics company, today presented the most contemporary analysis of the HELIOS-B Phase 3 study of vutrisiran for the treatment of ATTR amyloidosis with cardiomyopathy (ATTR-CM) as a late-breaking abstract at the Heart Failure 2025 Congress, a scientific congress of the European Society of Cardiology, taking place May 17-20 in Belgrade, Serbia. The results demonstrate that vutrisiran, which rapidly knocks down transthyretin, reduces key cardiovascular (CV) events such as CV hospitalizations, and heart failure (HF) hospitalizations. Additionally, in the analysis, urgent HF visits were reduced by 46% (95% CI: 0.30, 0.98; p = 0.041) in the overall population during the double-blind period, compared to placebo. These CV events often precede all-cause mortality (ACM) and are key indicators of disease progression.

Importantly, results from the November 2024 data cut, including further follow up through up to 42 months, reinforce the primary HELIOS-B analysis showing vutrisiran’s effect on ACM, and further demonstrate that vutrisiran reduces CV mortality. Through 42 months, the risk of ACM was reduced by 36% (95% CI: 0.46, 0.88; p = 0.007) and the risk of CV mortality was reduced by 33% (95% CI: 0.47, 0.96; p = 0.038) in the overall population, compared to placebo. For both the primary analysis and the current analysis, vital status through 42 months was ascertained for over 99% of all randomized patients from the HELIOS-B study, underscoring the robustness of the results.

The study was conducted in a contemporary patient population with patients receiving robust background therapy, inclusive of treatment with a TTR stabilizer and SGLT2 inhibitors. The analysis of the HELIOS-B Phase 3 study, including mortality data through up to 42 months, was simultaneously published in JACC.

“From the primary analysis of HELIOS-B, we know that AMVUTTRA profoundly impacts all-cause mortality, while preserving patients’ functional capacity and quality of life,” said Pushkal Garg, M.D., Chief Medical Officer of Alnylam. “These new data—including the impact on mortality, on cardiovascular events and on urgent heart failure visits, the latter of which was reduced by nearly half—add to the story of consistency and magnitude of benefit. I remain impressed by the HELIOS-B results, which are noteworthy given the substantial use of heart failure treatments in the study population, and I believe they continue to reinforce AMVUTTRA as a clinically differentiated, first-line option for patients with ATTR-CM.”