Alnylam's New Helios-B Data

Data were presented at the American College of Cardiology’s Annual Scientific Session (ACC.25) held in Chicago, Illinois. These data build upon the body of clinical evidence which supported the recent FDA approval of Amvuttra (vutrisiran) for the treatment of the cardiomyopathy of wild-type or hereditary transthyretin-mediated amyloidosis in adults to reduce cardiovascular mortality, cardiovascular hospitalizations and urgent heart failure visits. Amvuttra is an RNAi therapeutic that works upstream to deliver rapid knockdown of transthyretin, addressing the disease at its source, with four subcutaneous doses per year.

Moderated Poster Presentations:

The Relationship Between Cardiac Structure, Function, and Clinical Outcomes and the Impact of Vutrisiran from the HELIOS-B Trial

New echocardiographic data from the HELIOS-B Phase III clinical trial, the largest systematic echocardiographic study in a pivotal trial, demonstrated that treatment with vutrisiran improved echocardiographic cardiac function. Vutrisiran treatment led to significant improvements in diastolic function and attenuation of declines in left ventricular (LV) and right ventricular (RV) systolic function at Month 18, compared to placebo. Baseline measures of LV and RV systolic function, as well as indices of diastolic function, were shown to provide important prognostic information beyond clinical characteristics and biomarker-based staging systems. Notably, worsening LV and RV systolic function over 18 months was significantly associated with an increased risk of subsequent all-cause death, highlighting the importance of these parameters in assessing disease progression. The improved clinical outcomes of patients receiving vutrisiran in HELIOS-B may be mediated by its impact on cardiac function.

Impact of Baseline Heart Failure Severity on Efficacy of Vutrisiran in Patients with Transthyretin Amyloidosis with Cardiomyopathy in the HELIOS-B Trial: A Subgroup Analysis

An exploratory subgroup analysis demonstrated that vutrisiran reduced all-cause mortality and recurrent cardiovascular events across a range of baseline heart failure severities in patients with ATTR-CM. The greatest benefit was observed in patients with earlier, less severe disease, underscoring the need for timely diagnosis and early intervention. Similar effects were seen in the monotherapy population and across additional endpoints, including functional capacity and cardiac biomarkers, reinforcing the efficacy of vutrisiran regardless of disease stage. These results were recently published in JACC. (see citation- Maurer M, Witteles  R, Garcia-Pavia P. et al. Impact of Heart Failure Severity on Vutrisiran Efficacy in Transthyretin Amyloidosis with Cardiomyopathy. JACC. null2025, 0 (0) . https://doi.org/10.1016/j.jacc.2025.03.477 

Maintenance or Improvement of Functional Capacity, Health Status, and Quality of Life with Vutrisiran in Patients with Transthyretin Amyloidosis with Cardiomyopathy: Data from the HELIOS-B Study

A separate analysis confirmed that vutrisiran significantly maintained or improved functional capacity, and patient-reported health status and quality of life, compared to placebo over 30 months. Greater proportions of patients treated with vutrisiran preserved or improved 6-minute walk test distance and Kansas City Cardiomyopathy Questionnaire scores at clinically meaningful thresholds. These findings provide further evidence of vutrisiran’s ability to deliver meaningful benefits beyond reducing mortality and cardiovascular events. These results were recently published in JACC. (see  citation- Sheikh F, Habib,G, Tan, W. et al. Impact of Vutrisiran on Functional Capacity and Quality of Life in Transthyretin Amyloidosis With Cardiomyopathy. JACC. null2025, 0 (0) . https://doi.org/10.1016/j.jacc.2025.03.454 

The HELIOS-B study continues to deliver a robust data package showcasing the unique, differentiated value of vutrisiran as a first-line treatment option that can enable patients with ATTR-CM to live longer, better and healthier lives,” said Dr. Pushkal Garg, Chief Medical Officer of Alnylam. “Data showing beneficial effects on cardiac systolic and diastolic function are novel and indicate the direct impact of vutrisiran in cardiac structure and function of patients living with ATTR-CM. These findings, together with the observed improvements in functional capacity, health status and quality of life, as well as the reductions in all-cause mortality and cardiovascular events, demonstrate the rapid, broad, and sustained impacts of vutrisiran on ATTR-CM and underscore the importance of early intervention for this progressive and ultimately fatal disease.”