Targeting APOC3 with Olezarsen in Moderate Hypertriglyceridemia

作者：Brian A. Bergmark, Nicholas Marston, Thomas A Prohaska, Veronica Alexander, André Zimerman, Filipe A. Moura, Yu Mi Kang, Julia Weinland, Sabina A. Murphy, Erica L. Goodrich, S. M. Zhang, Dan Li, Maciej Banach, Erik Stroes, Michael T. Lu, Sotirios Tsimikas, Robert P. Giugliano, Marc S. Sabatine · 发表于：New England Journal of Medicine · 年份：2025 · DOI：10.1056/nejmoa2507227 · 被引用次数：61 · 研究领域：Lipid metabolism and disorders、Diabetes, Cardiovascular Risks, and Lipoproteins、Glycosylation and Glycoproteins Research

BACKGROUND: -acetylgalactosamine-conjugated antisense oligonucleotide that targets the messenger RNA of apolipoprotein C-III, which inhibits triglyceride clearance. METHODS: In this phase 3, international, double-blind, randomized, placebo-controlled trial, we enrolled patients with moderate hypertriglyceridemia (triglyceride level, 150 to 499 mg per deciliter) and elevated cardiovascular risk or with severe hypertriglyceridemia (triglyceride level, ≥500 mg per deciliter) and randomly assigned them in a 1:3 ratio to a 50-mg or 80-mg cohort. The patients were then randomly assigned in a 3:1 ratio to receive monthly subcutaneous olezarsen or matching placebo within each cohort. The primary outcome was the least-squares mean percent change in triglyceride level from baseline to 6 months among the patients with moderate hypertriglyceridemia, reported as the difference between each olezarsen dose group and the placebo group (the placebo-adjusted change). RESULTS: A total of 1349 patients (254 in the olezarsen 50-mg group, 766 in the olezarsen 80-mg group, and 329 in the placebo group) were included in the primary efficacy analysis. The median age was 64 years, 40% of the patients were women, and the median triglyceride level at baseline was 238.5 mg per deciliter (interquartile range, 190.5 to 307.5). At 6 months, the placebo-adjusted least-squares mean change in triglyceride level was -58.4 percentage points (95% confidence interval [CI], -65.1 to -51.7; P<0.001) in the olezarsen...