HELIOS-B: 12-month results from the open-label extension period of vutrisiran in patients with transthyretin amyloidosis with cardiomyopathy

Abstract Background Transthyretin amyloidosis with cardiomyopathy (ATTR-CM) is a progressive and fatal disease characterized by deposition of misfolded transthyretin protein in the heart. Vutrisiran, a subcutaneously administered RNA interference therapy, inhibits the production of hepatic transthyretin leading to rapid knockdown of the pathogenic protein. Over the 33–36-month (M), double-blind (DB) period of HELIOS-B, vutrisiran treatment lowered the risk of the primary composite endpoint of all-cause mortality (ACM) and recurrent cardiovascular (CV) events vs placebo in both the overall population and the monotherapy population (patients not on tafamidis at baseline). Patients completing the DB period were eligible to enter a 2-year open-label extension (OLE). Purpose To present 1-year efficacy and safety data from the OLE of HELIOS-B. Methods Following completion of the DB period (up to 36 months), patients could enter the 2-year OLE period in which all patients received vutrisiran 25 mg q3M. Efficacy endpoints evaluated over the OLE period include mortality and CV events (collected at M6, 12, 18, and 24). The ACM secondary endpoint was prespecified for analysis up to M42 from the start of the DB period, which included data from up to 6M of the OLE; this was expected to increase statistical precision and power since former placebo patients in the OLE would not yet have experienced mortality benefit. Results Overall, 654 patients received treatment in HELIOS-B (vutrisiran n=326; placebo n=328). Of 477 patients who completed DB treatment, 462 (96.9%; vutrisiran n=241; placebo n=221) entered the OLE period (96.9% of eligible patients who completed HELIOS-B study). A vital status sweep at OLE M6 (November 2024) resulted in 99% data ascertainment, consistent with the primary analysis ascertainment of 99%. Efficacy and safety results at OLE M12 will be presented. Conclusion During the DB period of HELIOS-B, vutrisiran demonstrated significant clinical benefit versus placebo in patients with ATTR-CM. The impact of early vs delayed initiation of vutrisiran in this population will be elucidated in the OLE M12 data.