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索他洛尔:肺动脉高压领域的新药。

Sotatercept: New drug on the horizon of pulmonary hypertension.

作者信息

Madonna Rosalinda, Biondi Filippo

机构信息

Department of Surgical, Medical and Molecular Pathology and Critical Area, Cardiology Division, University of Pisa, Pisa, Italy.

Department of Surgical, Medical and Molecular Pathology and Critical Area, Cardiology Division, University of Pisa, Pisa, Italy.

出版信息

Vascul Pharmacol. 2024 Dec;157:107442. doi: 10.1016/j.vph.2024.107442. Epub 2024 Nov 19.

Abstract

Sotatercept (brand name WINREVAIR, developed by Merck) is an activin receptor type IIA-Fc (ActRIIA-Fc), working by sequestering free activins. Sotatercept restores the balance between the activin proliferative pathway and the bone morphogenic protein (BMP) antiproliferative pathway in the pulmonary arterial cirulation. Sotatercept recently received approval in the USA and in Europe for the treatment of adults with pulmonary arterial hypertension (PAH) Group 1, on top of background PAH therapy to increase exercise capacity, improve WHO functional class and reduce the risk of clinical worsening events. Nevertheless, several studies are ongoing to investigate the potential adverse reactions of the drug especially at the haematological level. We provide an overview of the clinical and preclinical evidence of the targeting the activing pathway through sotatercept on the treatment of PAH. We also discuss what other possibilities there are for the application of sotatercept in the setting of pulmonary hypertension other than PAH Group 1.

摘要

索他西普(商品名WINREVAIR,由默克公司研发)是一种IIA型激活素受体-融合蛋白(ActRIIA-Fc),通过螯合游离激活素来发挥作用。索他西普可恢复肺动脉循环中激活素增殖途径与骨形态发生蛋白(BMP)抗增殖途径之间的平衡。索他西普最近在美国和欧洲获得批准,用于治疗1类肺动脉高压(PAH)成人患者,在PAH背景治疗基础上增加运动能力、改善世界卫生组织功能分级并降低临床恶化事件风险。然而,目前正在进行多项研究以调查该药物的潜在不良反应,尤其是血液学方面的不良反应。我们概述了通过索他西普靶向激活素途径治疗PAH的临床和临床前证据。我们还讨论了除1类PAH外,索他西普在肺动脉高压背景下应用的其他可能性。

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