RNAi therapeutics company Alnylam Pharmaceuticals has reported positive results from the HELIOS-B Phase 3 study of Amvuttra (vutrisiran) for the treatment of ATTR amyloidosis with cardiomyopathy (ATTR-CM).
The topline results from the randomised, double-blind, placebo-controlled multicentre global HELIOS-B trial was announced in June.
The trial assessed the efficacy and safety of vutrisiran in reducing all-cause mortality and recurrent cardiovascular events as a primary composite endpoint in patients with ATTR-CM.
The study randomised 655 adult patients to receive vutrisiran 25mg or placebo subcutaneously once every three months during a double-blind treatment period of up to 36 months.
After the double-blind period, all eligible patients remaining in the study were able to receive vutrisiran in an open-label extension period of HELIOS-B.
The HELIOS-B study achieved statistical significance for all 10 of its primary and secondary endpoints in both the overall and monotherapy populations.
In the trial, vutrisiran significantly reduced the risk of death and cardiovascular events compared to placebo.
In the overall group, the drug cut the risk of all-cause mortality and recurrent cardiovascular events by 28%.
Specifically, it reduced mortality by 31% during the double-blind period and by 36% over 42 months.
In the monotherapy group, vutrisiran decreased the risk of all-cause mortality and recurrent cardiovascular events by 33%, and reduced mortality by 35% over 42 months.
The safety and tolerability of the drug were in line with previous studies and the currently approved patient population.
Alnylam Pharmaceuticals chief medical officer Pushkal Garg said: “With this study, we have demonstrated that the rapid knockdown of toxic TTR seen with vutrisiran improves survival, and reduces cardiovascular hospitalisations and disease progression versus placebo, with benefits consistently observed across populations and regardless of background stabiliser use.”
Alnylam Pharmaceuticals is now planning to begin global regulatory submissions for Amvuttra later this year.
This includes filing a supplemental new drug application with the US Food and Drug Administration (FDA) using a priority review voucher.
In the US, vutrisiran is approved for treating the polyneuropathy associated with hereditary transthyretin-mediated amyloidosis (hATTR amyloidosis) in adults.
In Europe and the UK, vutrisiran was approved in 2022 for the treatment of hATTR amyloidosis in adult patients with stage 1 or stage 2 polyneuropathy.
