New findings presented at the ESC Congress 2024 reveal that vutrisiran, a novel RNA interference (RNAi) therapeutic, significantly reduces mortality, cardiovascular events, and disease progression markers in patients with transthyretin amyloidosis with cardiomyopathy (ATTR-CM).
Professor Marianna Fontana of University College London and Royal Free Hospital, UK, explained, “ATTR is a progressive and often fatal disease characterized by the accumulation of misfolded transthyretin protein, which forms amyloid deposits that can severely damage the heart. Our study evaluated vutrisiran, which targets transthyretin production, and the results were very promising”.
The HELIOS-B trial, a randomized, double-blind study, involved patients with hereditary or wild-type ATTR-CM who had confirmed cardiac amyloidosis through echocardiography. The trial included 655 participants from 87 centers across 26 countries, with a median age of 76.5 years and 92.5% male. Participants were randomized to receive either vutrisiran 25 mg or a placebo subcutaneously every three months for up to 36 months. If patients were already on the disease stabilizer tafamidis, they continued this treatment.
The study’s primary endpoints focused on a composite of all-cause mortality and recurrent cardiovascular events at month 33, both in the overall population and in patients receiving vutrisiran monotherapy. Secondary endpoints included all-cause mortality over 42 months, functional capacity as measured by the 6-minute walk test, quality of life via the Kansas City Cardiomyopathy Questionnaire Overall Summary, and New York Heart Association (NYHA) class.
The results were significant: vutrisiran reduced the risk of all-cause mortality and recurrent cardiovascular events by 28% in the overall population (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 a prespecified subgroup analysis, patients on background tafamidis therapy also showed a more than 20% reduction in the composite endpoint (HR 0.79; 95% CI 0.51–1.21).
Over 42 months, vutrisiran reduced all-cause mortality by 36% in the overall population (HR 0.64; 95% CI 0.46–0.90; p=0.01) and by 35% in the monotherapy group (HR 0.65; 95% CI 0.44–0.97; p=0.045) compared to placebo. Secondary outcomes related to functional capacity, health status, and quality of life were also significantly improved with vutrisiran.
Vutrisiran was well tolerated, with most adverse events being mild to moderate in severity. The rates of adverse events leading to study drug discontinuation were comparable between the vutrisiran (3.1%) and placebo (4.0%) groups.
Professor Fontana concluded, “Vutrisiran has shown to be highly effective and well-tolerated in a patient population reflective of those commonly seen in clinical practice. The consistent benefits observed, regardless of background tafamidis therapy, suggest that vutrisiran could potentially become the new standard of care. This trial is also notable as it marks the first demonstration of the benefits of gene silencers in any type of cardiomyopathy”.
The ESC Congress 2024, held both onsite in London and online from August 30 to September 2, is the world’s largest gathering of cardiovascular professionals, dedicated to advancing cardiovascular medicine and improving patient outcomes.
As reported by pharmabiz.com, the European Society of Cardiology (ESC) represents healthcare professionals from over 150 countries, all working towards the common goal of extending and enhancing the lives of individuals with cardiovascular disease.