Alnylam Pharmaceuticals, Inc. (Nasdaq: ALNY), a leading RNAi therapeutics company, has announced detailed results from the HELIOS-B Phase 3 study of vutrisiran, an investigational RNAi therapeutic for the treatment of ATTR amyloidosis with cardiomyopathy (ATTR-CM). The data were presented at the European Society of Cardiology (ESC) Congress 2024 in London and simultaneously published in The New England Journal of Medicine.
The HELIOS-B study met all 10 of its primary and secondary endpoints in both the overall and monotherapy populations, with statistical significance. The study enrolled patients primarily with New York Heart Association (NYHA) Class I or II wild-type disease, who were diagnosed using non-invasive methods and were receiving standard treatments such as tafamidis and SGLT2 inhibitors.
Treatment with vutrisiran significantly reduced the risk of death and cardiovascular events compared to placebo. In the overall population, vutrisiran reduced the risk of all-cause mortality and recurrent cardiovascular events by 28%, with a 31% reduction in mortality during the double-blind period and a 36% reduction up to 42 months. In the monotherapy population, vutrisiran reduced the risk of all-cause mortality and recurrent cardiovascular events by 33%, with a 35% reduction in mortality up to 42 months.
Vutrisiran also showed benefits over placebo in several clinical measures of disease progression, including the 6-Minute Walk Test, Kansas City Cardiomyopathy Questionnaire, NYHA Class, and the cardiac biomarker NT-proBNP. Subgroup analyses indicated consistent benefits across key patient segments, including those receiving background tafamidis, with greater efficacy trends seen in patients with earlier disease stages.
The safety and tolerability of vutrisiran were consistent with established profiles from approved patient populations and earlier studies.
Dr. Marianna Fontana, a HELIOS-B investigator and Professor of Cardiology at University College London, highlighted the significance of the study, noting that vutrisiran’s ability to reduce all-cause mortality and cardiovascular events represents a significant advancement in ATTR amyloidosis treatment. Alnylam’s Chief Medical Officer, Dr. Pushkal Garg, emphasized that the results suggest vutrisiran could become a new standard of care for ATTR-CM, a progressive and fatal disease with limited treatment options.
Alnylam is working urgently to submit these data to regulatory authorities to make vutrisiran available to patients worldwide.
Primary and Secondary Endpoints
The HELIOS-B study evaluated primary and secondary endpoints, including composite all-cause mortality and recurrent cardiovascular events, 6-Minute Walk Test performance, Kansas City Cardiomyopathy Questionnaire scores, and NYHA Class improvements. Subgroup analyses consistently showed benefits across patient segments, including those on background stabilizers like tafamidis, and indicated greater benefits in patients with earlier disease stages. Notably, vutrisiran led to significant reductions in NT-proBNP, an established cardiac biomarker predictive of mortality in ATTR-CM.
These findings underscore the potential of vutrisiran to offer substantial benefits to patients with ATTR-CM, especially when initiated in the early stages of the disease.
