Vutrisiran : Alnylam Pharmaceuticals reveals positive results from HELIOS-B Phase 3 study

Alnylam Pharmaceuticals, Inc. (Nasdaq: ALNY), a pioneer in RNA interference (RNAi) therapeutics, has unveiled promising results from the HELIOS-B Phase 3 study of vutrisiran, a groundbreaking investigational treatment for ATTR amyloidosis with cardiomyopathy (ATTR-CM). The findings were showcased in a Hot Line session at the European Society of Cardiology (ESC) Congress 2024 and simultaneously published in The New England Journal of Medicine.

The HELIOS-B study, a critical Phase 3 trial, met all 10 of its primary and secondary endpoints with statistical significance. Enrolled patients, mostly in New York Heart Association (NYHA) Class I or II and diagnosed through non-invasive methods, were receiving standard treatments like tafamidis and SGLT2 inhibitors, reflecting a contemporary ATTR-CM patient population.

Key Findings from the HELIOS-B Study

The results highlight a substantial reduction in both mortality and cardiovascular events with vutrisiran compared to placebo. In the overall study population, vutrisiran reduced the risk of all-cause mortality and recurrent cardiovascular events by 28%. Notably, mortality was reduced by 31% during the double-blind period and by 36% over 42 months. For the monotherapy group, vutrisiran led to a 33% reduction in mortality risk and a 35% decrease in mortality over 42 months. Although a non-significant 30% reduction in mortality was observed in the double-blind period of the monotherapy group (p-value 0.1179), the overall results were robust.

Moreover, vutrisiran showed improvements across several clinical measures of disease progression, including the 6-Minute Walk Test, the Kansas City Cardiovascular Questionnaire, NYHA Class, and the cardiac biomarker NT-proBNP. Subgroup analyses revealed consistent benefits across all key patient segments, including those receiving background tafamidis, with greater efficacy observed in patients with earlier stages of the disease.

Safety and Tolerability

The safety and tolerability profiles of vutrisiran were consistent with those established in previously approved patient populations and earlier studies. This aligns with the therapeutic expectations for a novel treatment targeting the progressive nature of ATTR-CM.

Expert Insights

Dr. Marianna Fontana, HELIOS-B investigator and Professor of Cardiology at University College London, emphasized the study’s significance. “The HELIOS-B results represent a major advancement in treating ATTR amyloidosis with cardiomyopathy. Vutrisiran’s ability to dramatically reduce mortality and cardiovascular events is noteworthy, particularly in a contemporary setting where early diagnosis and robust standard care are prevalent. This data suggests that vutrisiran could significantly benefit patients in earlier disease stages by preserving functional capacity and quality of life.”

Pushkal Garg, M.D., Chief Medical Officer at Alnylam Pharmaceuticals, expressed enthusiasm about the findings. “The detailed HELIOS-B data presented at the ESC Congress 2024 demonstrate that vutrisiran’s rapid TTR knockdown improves survival, reduces cardiovascular hospitalizations, and slows disease progression. While regulatory review is pending, these results indicate vutrisiran’s potential as a new standard of care for ATTR-CM, a disease with limited treatment options.”

Looking Ahead

Alnylam Pharmaceuticals is moving swiftly to advance vutrisiran’s development, working with urgency to file necessary regulatory submissions. The company extends gratitude to all involved in the study, including patients, caregivers, and investigators.