A NOVEL RNA interference (RNAi) therapeutic significantly reduced mortality and cardiovascular events in patients with transthyretin amyloidosis with cardiomyopathy (ATTR-CM). ATTR-CM is a progressive and fatal disease characterized by amyloid deposits that often damage the heart, leading to cardiomyopathy. The HELIOS-B trial investigated vutrisiran, a novel RNA interference (RNAi) therapeutic, which targets transthyretin production, to assess its effectiveness in improving clinical outcomes for patients with ATTR-CM.
In this randomised, double-blind trial, 655 patients from 87 centres across 26 countries were assigned to receive either vutrisiran or a placebo every three months for up to 36 months. The primary endpoints were a composite of all-cause mortality and recurrent cardiovascular events, assessed both in the overall population and specifically in those receiving vutrisiran monotherapy (without tafamidis).
Trial results indicated that vutrisiran significantly reduced the risk of all-cause mortality and recurrent cardiovascular events by 28% in the overall population (hazard ratio [HR] 0.72; 95% CI 0.56–0.93; p=0.01) and by 33% in the monotherapy group (HR 0.67; 95% CI 0.49–0.93; p=0.016). In those on background tafamidis, the composite of all-cause mortality and recurrent cardiovascular events was reduced by more than 20% (HR 0.79; 95% CI 0.51–1.21). Additionally, vutrisiran decreased all-cause mortality by 36% (HR 0.64; 95% CI 0.46–0.90; p=0.01) over 42 months in the overall population and by 35% (HR 0.65; 95% CI 0.44–0.97; p=0.045) in the monotherapy group, compared to placebo.
Secondary endpoints, including improvements in functional capacity, health status, and quality of life, also showed benefits for those treated with vutrisiran. The safety profile was favourable, with most adverse events being mild or moderate, and discontinuation rates due to adverse events were similar between the vutrisiran and placebo groups.
In conclusion, vutrisiran demonstrated efficacy in reducing mortality and cardiovascular events, with an acceptable safety profile, suggesting its potential as a new standard of care for patients with ATTR-CM. This trial is also the first to explore the benefit of gene silencers in cardiomyopathy treatment.
Abigail Craig | EMJ
Reference
Fontana M et al. HELIOS-B – Primary results from phase 3 study of vutrisiran in patients with transthyretin amyloidosis with cardiomyopathy. ESC Congress 2024, 30 August 2024.
