Hot Line: Vutrisiran offers a new lifeline for patients with ATTR-CM
31 Aug 2024
As presented yesterday by Professor Marianna Fontana (University College London, Royal Free Hospital - London, UK), the HELIOS-B trial investigated vutrisiran, a novel RNAi therapeutic that targets transthyretin production, in patients with transthyretin amyloidosis with cardiomyopathy (ATTR-CM).
In this double-blind trial, 655 patients with ATTR-CM (hereditary or wild-type) with evidence of cardiac amyloidosis were randomised to receive vutrisiran 25 mg or placebo administered subcutaneously once every 3 months for up to 36 months. Any background tafamidis treatment was continued. The primary endpoints were all-cause mortality and recurrent CV events, when the last patient reached month 33, assessed in the overall population and in patients taking vutrisiran monotherapy (i.e. those not taking tafamidis at baseline).
The trial met the primary endpoints.
Vutrisiran significantly reduced the risk of all-cause mortality and recurrent CV 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 population (HR 0.67; 95% CI 0.49–0.93; p=0.016). In a prespecified subgroup analysis, the composite was reduced by more than 20% in patients on background tafamidis (HR 0.79; 95% CI 0.51–1.21).
Vutrisiran reduced all-cause mortality over 42 months by 36% in the overall population (HR 0.64; 95% CI 0.46–0.90; p=0.01) and by 35% in the monotherapy population (HR 0.65; 95% CI 0.44–0.97; p=0.045) vs. placebo. Other secondary endpoints related to functional capacity, health status and quality of life were significantly improved with vutrisiran vs. placebo. Adverse events leading to study drug discontinuation were similar in the vutrisiran (3.1%) and placebo (4.0%) groups.
Prof. Fontana concluded: “Vutrisiran was highly effective and well tolerated in this contemporary population representative of patients that we see in our clinics, with consistent benefits regardless of background tafamidis therapy. Our findings indicate that vutrisiran has the potential to become the new standard of care. This trial is also important as it is the first to show the benefit of gene silencers in any type of cardiomyopathy.”
