HELIOS-B: Vutrisiran candidate for SoC in ATTR cardiomyopathy

Vutrisiran reduced all-cause mortality and recurrent cardiovascular events in patients with transthyretin amyloidosis (ATTR) with cardiomyopathy versus placebo, despite a substantial proportion of the phase 3 HELIOS-B study population being on tafamidis background therapy.

“ATTR cardiomyopathy leads to heart failure, arrhythmias, hospitalisations, and reduced survival,” said Prof. Marianna Fontana (University College London, UK) [1]. “We are, however, seeing a trend towards earlier diagnosis, improved management for heart failure, and better treatment options for ATTR cardiomyopathy, such as tafamidis and SGLT2 inhibitors.” Prof. Fontana and colleagues investigated the RNA interference therapeutic vutrisiran in patients with ATTR cardiomyopathy in the double-blind, randomised-controlled, phase 3 HELIOS-B trial (NCT04153149).

The participants (n=655) were randomised 1:1 to vutrisiran or placebo every 12 weeks for up to 36 months. The primary endpoint was a composite of all-cause mortality and recurrent cardiovascular events at 36 months. “Approximately 40% of the participants were on tafamidis at baseline, raising the bar for vutrisiran to demonstrate its efficacy,” emphasised Prof. Fontana.

The primary endpoint was met, with a hazard ratio of 0.72, and a P-value of 0.012 (95% CI 0.55–0.93) [1,2]. “This effect was driven by both components of the primary endpoint,” added Prof. Fontana [1]. Important secondary endpoints were also in favour of the vutrisiran arm, including change in the 6-minute walk test at 30 months (LS mean difference 26.46; P=0.00008) and Kansas City Cardiomyopathy Questionnaire (KCCQ) Overall Score change at 30 months (LS mean difference 5.80; P=0.0008).

The safety profiles of vutrisiran and placebo were similar, with 67.1% and 61.7% of the participants experiencing serious adverse events (AEs) in the placebo and vutrisiran arm, respectively. In addition, there were no AEs that were typical for vutrisiran.

“Vutrisiran has the potential to become a standard-of-care for previously untreated patients with ATTR cardiomyopathy and for those who progress on stabilising therapies,” concluded Prof. Fontana.

1. 
   
   1. Fontana M, et al. HELIOS-B: Primary results from phase 3 study of vutrisiran in patients with transthyretin amyloidosis with cardiomyopathy. HOTLINE 1, ESC Congress 2024, 30 Aug–02 Sept, London, UK.
   2. Fontana M, et al. N Engl J Med 2024; Aug 30. DOI: 10.1056/NEJMoa2409134.

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Posted on 7 November 2024