Therapeutic advances in the Lp(a) battle: what do we know and what are the most awaited novelties in the field ?

IF 3.8 3区医学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY

Current opinion in lipidology Pub Date : 2025-03-20 DOI:10.1097/MOL.0000000000000981

Marc Jean-Gilles, Baris Gencer

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引用次数: 0

Abstract

Purpose of review: To review the latest advances in lipoprotein(a) [Lp(a)] treatment, focusing on the impact of currently available lipid-lowering therapies and highlighting the highly anticipated and most developed RNA-based therapies.

Recent findings: Lp(a) is a key genetically determined cardiovascular risk modifier linked to myocardial infarction and calcific aortic stenosis development and progression. Conventional lipid-lowering therapies have no substantial effect on circulating Lp(a) levels, leading current guidelines to focus on managing traditional cardiovascular risk factors. New therapies, including antisense oligonucleotides and small interfering RNAs, target Lipoprotein(A) [LPA] gene translation to reduce apo(a) synthesis and Lp(a) particles formation. The most advanced candidates, pelacarsen, olpasiran, and lepodisiran, have shown promising Lp(a) reductions, ranging from -35% to -101% in Phase 1 and 2 trials. Phase 3 studies will clarify their effects on cardiovascular outcomes and address concerns about extremely low Lp(a) levels and safety.

Summary: The RNA-based agents pelacarsen, olpasiran, and lepodisiran represent the most advanced developments in this field. Ongoing Phase 3 trials, expected to be finalized between 2025 and 2029, will be crucial in determining their efficacy in improving cardiovascular outcomes and their safety profiles.

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Lp(a)之战的治疗进展：我们知道什么？该领域最令人期待的新奇事物是什么？

综述目的：回顾脂蛋白(a) [Lp(a)]治疗的最新进展，重点介绍目前可用的降脂疗法的影响，并重点介绍备受期待和最发达的rna疗法。最近的研究发现：Lp(a)是一个关键的基因决定的心血管危险调节剂，与心肌梗死和钙化主动脉狭窄的发生和进展有关。传统的降脂疗法对循环脂蛋白(a)水平没有实质性影响，导致目前的指南将重点放在管理传统的心血管危险因素上。新的治疗方法，包括反义寡核苷酸和小干扰rna，以脂蛋白(A) [LPA]基因翻译为目标，减少载脂蛋白(A)的合成和Lp(A)颗粒的形成。最先进的候选药物pelacarsen， olpasiran和lepodisiran在1期和2期试验中显示出有希望的Lp(a)降低，范围从-35%到-101%。3期研究将阐明其对心血管预后的影响，并解决极低Lp(a)水平和安全性的担忧。摘要：基于rna的药物pelacarsen、olpasiran和lepodisiran代表了该领域的最新进展。正在进行的3期试验预计将在2025年至2029年之间完成，这将是确定它们在改善心血管结局和安全性方面的有效性的关键。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Current opinion in lipidology 医学-内分泌学与代谢

CiteScore

6.70

自引率

4.50%

发文量

审稿时长

6-12 weeks

期刊介绍： With its easy-to-digest reviews on important advances in world literature, Current Opinion in Lipidology offers expert evaluation on a wide range of topics from six key disciplines including nutrition and metabolism, genetics and molecular biology, and hyperlipidaemia and cardiovascular disease. Published bimonthly, each issue covers in detail the most pertinent advances in these fields from the previous year. This is supplemented by a section of Bimonthly Updates, which deliver an insight into new developments at the cutting edge of the disciplines covered in the journal.