From clinical development to real-world outcomes with inclisiran.

IF 3.8 3区医学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY Current opinion in lipidology Pub Date : 2024-12-01 Epub Date: 2024-09-27 DOI:10.1097/MOL.0000000000000954

Derek L Connolly, Vinoda Sharma, Kausik K Ray

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Abstract

Purpose of review: Inclisiran is a small interfering RNA that blocks hepatocyte production of the PCSK9 (proprotein convertase subtilisin/kexin type 9) protein by specifically targeting PCKS9 mRNA in the cytoplasm. This results in reduced degradation of LDL receptors and thus lowers LDL cholesterol by around 50% in addition to other lipid-lowering therapies. beyond 6 years of therapy. This review covers the latest published data and outlines future studies currently in process.

Recent findings: To date, half a million doses have been given worldwide with no untoward adverse events thus far. The twice-yearly injections make it potentially very user-friendly. The large phase 3a trials saw no diminution of effect with time up to nearly 7 years. Very large phase 3b randomized controlled trials are underway and may produce significant reductions in major adverse cardiovascular events.

Summary: Inclisiran has been evaluated in numerous trials, primarily the ORION 9 26 , ORION 10 27 and ORION 11 28 studies, which demonstrated that in patients already on maximally tolerated statin therapy, biannual inclisiran injections reduced LDL cholesterol by up to 52% compared to placebo with a good safety profile. The only observed side effects were mild and transient at the injection site. As mentioned in the accompanying video, this adds to our armamentarium of lipid treatments.

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克利西兰从临床开发到实际应用结果

综述目的：Inclisiran是一种小干扰RNA，它通过特异性靶向细胞质中的PCKS9 mRNA，阻断肝细胞产生PCSK9（9型碱性磷酸酶）蛋白。这将减少低密度脂蛋白受体的降解，从而在其他降脂疗法的基础上将低密度脂蛋白胆固醇降低约 50%。本综述涵盖了最新发表的数据，并概述了目前正在进行的未来研究：最近的研究结果：迄今为止，全球已注射了 50 万剂，未发生任何不良事件。每年两次的注射使其可能非常方便用户使用。大型 3a 期试验显示，在近 7 年的时间里，疗效没有减弱。总结：Inclisiran 已在多项试验中进行了评估，主要是 ORION 926、ORION 1027 和 ORION 1128 研究，这些研究表明，与安慰剂相比，已接受最大耐受他汀类药物治疗的患者每年注射两次的 inclisiran 可使低密度脂蛋白胆固醇降低 52%，且安全性良好。唯一观察到的副作用是注射部位的轻微和短暂副作用。正如附带视频中提到的，这为我们的血脂治疗手段增添了新的内容。

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.