Vutrisiran in Patients with Transthyretin Amyloidosis with Cardiomyopathy

Transthyretin amyloidosis with cardiomyopathy (ATTR-CM) is a progressive, fatal disease caused by misfolded transthyretin proteins accumulating as amyloid fibrils in the heart. Vutrisiran is a subcutaneously administered RNA interference therapeutic agent designed to inhibit hepatic transthyretin production. This double-blind, randomized controlled trial (HELIOS-B) investigated the efficacy of vutrisiran (25 mg every 12 weeks) versus placebo in 655 patients over 36 months.

Results showed that vutrisiran significantly reduced the risk of death and recurrent cardiovascular events (hazard ratio in the overall population, 0.72; P=0.01) and preserved functional capacity, as measured by the 6-minute walk test (mean difference: 26.5 meters; P<0.001) and Kansas City Cardiomyopathy Questionnaire-Overall Summary (mean difference: 5.8 points; P<0.001). Patients receiving vutrisiran showed a rapid and sustained reduction in serum transthyretin levels (81% decrease) without increased serious adverse effects compared to placebo.

Transthyretin amyloidosis with cardiomyopathy (ATTR-CM) is a progressive, fatal disease caused by misfolded transthyretin proteins accumulating as amyloid fibrils in the heart. Vutrisiran is a subcutaneously administered RNA interference therapeutic agent designed to inhibit hepatic transthyretin production. This double-blind, randomized controlled trial (HELIOS-B) investigated the efficacy of vutrisiran (25 mg every 12 weeks) versus placebo in 655 patients over 36 months.

Results showed that vutrisiran significantly reduced the risk of death and recurrent cardiovascular events (hazard ratio in the overall population, 0.72; P=0.01) and preserved functional capacity, as measured by the 6-minute walk test (mean difference: 26.5 meters; P<0.001) and Kansas City Cardiomyopathy Questionnaire-Overall Summary (mean difference: 5.8 points; P<0.001). Patients receiving vutrisiran showed a rapid and sustained reduction in serum transthyretin levels (81% decrease) without increased serious adverse effects compared to placebo.