Vutrisiran in Transthyretin Amyloidosis

作者：Ronald Witteles, Pablo García‐Pavía, Caroline Morbach, Julian D. Gillmore, Mark Taylor, Isabel Conceição, William B White, C. Kwok, Marianne T. Sweetser, Katherine L. Boyle, David Adams · 发表于：JACC Advances · 年份：2025 · DOI：10.1016/j.jacadv.2025.102066 · 被引用次数：7 · 研究领域：Amyloidosis: Diagnosis, Treatment, Outcomes、Skin and Cellular Biology Research、Nuclear Structure and Function

BACKGROUND: Vutrisiran is an RNA interference therapeutic that has demonstrated efficacy for the treatment of patients with transthyretin amyloidosis (ATTR) with polyneuropathy and cardiomyopathy in the phase 3 HELIOS-A and HELIOS-B studies, respectively. During the initial randomized treatment periods of these studies, vutrisiran was well tolerated and had an acceptable safety profile. OBJECTIVES: This pooled safety analysis aimed to evaluate the safety of vutrisiran in a large population of patients with hereditary ATTR and wild-type ATTR who received treatment for up to 58 months in HELIOS-A and HELIOS-B. METHODS: Data from patients who received at least one dose of vutrisiran at any time during the HELIOS-A or HELIOS-B studies were included in this pooled safety analysis. For reference, data from the external placebo arm of HELIOS-A (APOLLO placebo) and the placebo arm of HELIOS-B studies were included. Exposure-adjusted adverse event rates (AERs) and serious AERs were calculated per 100 patient-years. RESULTS: The combined vutrisiran group comprised 707 patients (HELIOS-A vutrisiran group: n = 160; HELIOS-B vutrisiran group: n = 547) with a mean age at symptom onset of 68.5 years; 30.3% had hereditary ATTR. These patients had a median (range) treatment duration of 33.4 months (0.0-57.8) and a cumulative exposure of 1,518.9 patient-years. In the combined vutrisiran group, AERs and serious AERs for specific adverse events were comparable to those reported in either of the ...