肺动脉高压治疗药物--索特西普  

A Therapeutic Drug for Pulmonary Arterial Hypertension:Sotatercept

作　　者：陈鑫 王帅飞 孟欢欢 杜勤超 CHEN Xin;WANG Shuai-fei;MENG Huan-huan;DU Qin-chao(Department of Pharmacy,Qiantang Campus,Sir Run Run Shaw Hospital,Zhejiang University School of Medicine,Hangzhou 310018,China;Department of Pharmacy,Sir Run Run Shaw Hospital,Zhejiang University School of Medicine,Hangzhou 310016,China)

机构地区：[1]浙江大学医学院附属邵逸夫医院钱塘院区药学部,杭州310018 [2]浙江大学医学院附属邵逸夫医院药学部,杭州310016

出　　处：《中国合理用药探索》2025年第1期17-21,共5页Chinese Journal of Rational Drug Use

基　　金：浙江省医药卫生科技计划(2024KY099);2024年浙江省药学会公立医疗机构药品集采规范化管理专项科研资助项目(2024ZYYJ19)。

摘　　要：索特西普(sotatercept)是一种激活素受体ⅡA(ActRⅡA)融合蛋白,由美国默沙东公司研发,并于2024年3月26日获得美国食品药品监督管理局批准上市,用于肺动脉高压(PAH)的治疗。索特西普是首个用于PAH治疗的激活素信号抑制剂,能够选择性地与转化生长因子-β(TGF-β)超家族成员配体结合,通过改善促增殖和抗增殖信号之间的平衡来调节肺动脉血管的增殖和抑制,从而逆转肺部小动脉血管的过度增殖和重构。临床研究结果显示,索特西普能够显著改善PAH患者的运动能力,与基线相比,患者的6min步行距离(6MWD)增加了40.8m,肺血管阻力(PVR)、N-末端B型利钠肽原(NT-proBNP)水平以及世界卫生组织功能等级(WHO FC)等都得到了显著改善。此外,索特西普在PAH患者中也表现出良好的耐受性和安全性。目前,该药尚未在我国获批上市。本文对索特西普的作用机制、药动学特征以及临床研究进展等进行简要综述,以期为PAH的临床治疗提供一定的用药参考和理论依据。Sotatercept is a fusion protein of activin receptor typeⅡA(ActRⅡA)developed by Merck&Co.,Inc.,USA.It was approved by the U.S.Food and Drug Administration(FDA)on March 26,2024 for the treatment of pulmonary arterial hypertension(PAH).Sotatercept is the first-in-class activin signaling inhibitor forthe treatment of PAH,selectively binding to ligands within the transforming growth factor-β(TGF-β)superfamily.It regulates the proliferation and inhibition of pulmonary artery blood vessels by improving the balance between proliferative and anti-proliferative signals,thereby reversing excessive proliferation and remodeling of small pulmonary arteries.Clinical studies have demonstrated that sotatercept can significantly improve patients'exercise capacity,evidenced by a 40.8m increase in the 6-minute walk distance(6MWD)compared to baseline.Additionally,significant improvements have been observed in patients'pulmonary vascular resistance(PVR),N-terminal pro-brain natriuretic peptide(NT-proBNP)levels,and World Health Organization functional class(WHO FC).Furthermore,Sotercept has demonstrated good tolerability and safety in patients with PAH.Currently,Sotercept has not been approved for marketing in China.This article provides a brief review of the mechanism of action,pharmacokinetics characteristics,and clinical research progress of sotatercept,aiming to provide a reference and theoretical basis for the clinical treatment of PAH.

关 键 词：索特西普 肺动脉高压 激活素受体ⅡA 6MIN步行距离 世界卫生组织功能等级 

分 类 号：R972.4[医药卫生—药品] R543.2[医药卫生—药学]