Transthyretin amyloidosis (ATTR) is a progressive and fatal disease. Patients (pts) with hereditary or wild-type (h or wtATTR) amyloidosis frequently develop cardiomyopathy (CM). Vutrisiran, an RNA therapeutic is approved for the treatment of hATTR with polyneuropathy (hATTR-PN). Exploratory analyses of a predefined cardiac subpopulation in HELIOS-A demonstrated potential for vutrisiran to improve CM manifestations in pts with hATTR-PN.

Safety and efficacy of vutrisiran in ATTR-CM pts are being investigated in the ongoing HELIOS-B study. We hypothesize that rapid knockdown of TTR by vutrisiran provides benefit across a range of cardiac disease measures in pts with ATTR-CM.

HELIOS-B is a phase 3, randomized, double-blind, placebo (pbo)-controlled, multicenter study of vutrisiran in pts with ATTR-CM (wtATTR or hATTR). Eligible pts (18–85 yrs) had echocardiographic evidence of ATTR-CM, and ATTR amyloid deposition confirmed by diagnostic criteria, including cardiac scintigraphy. Inclusion criteria included a medical history of heart failure (HF) due to ATTR with≥1 prior HF hospitalization or clinical evidence of HF-related congestion requiring use of diuretics. At baseline (BL), pts were either not on tafamidis or were receiving tafamidis per the approved indication and dose for their country. Pts were randomized (1:1) to vutrisiran 25mg or placebo subcutaneously, once every 3 months (M) for up to 36M. The 2 primary endpoints were a composite of all-cause mortality and recurrent cardiovascular (CV) events (CV hospitalizations and urgent HF visits), assessed in the overall population and in the vutrisiran monotherapy group (defined as pts not on tafamidis at BL). A comprehensive set of exploratory endpoints comparing vutrisiran with pbo included biomarkers and additional assessments of outcomes. The pharmacodynamic effect of vutrisiran on serum TTR level was also assessed over 30M.

HELIOS-B completed enrollment (655 pts; 654 dosed) in August 2021 across 26 countries. Median age, 77 (45–85) years; ≥75 years old, 61%; male, 92.5%; on tafamidis at BL, 40%; mean (SD) BMI, 27 (3.7) kg/m². The treatment effect of vutrisiran on clinical manifestations of cardiac TTR amyloid involvement will be presented across select exploratory measures.

Vutrisiran has the potential to improve the cardiomyopathies associated with ATTR. The exploratory endpoint results will help further define the impact of vutrisiran across a range of cardiac measures in patients with ATTR-CM.