Hoeper Marius M, Gomberg-Maitland Mardi, Badesch David B, Gibbs J Simon R, Grünig Ekkehard, Kopeć Grzegorz, McLaughlin Vallerie V, Meyer Gisela, Olsson Karen M, Preston Ioana R, Rosenkranz Stephan, Souza Rogerio, Waxman Aaron B, Perchenet Loïc, Strait James, Xing Aiwen, Manimaran Solaiappan, Wang Xuelong, Miller Barry, Cornell Alexandra G, de Oliveira Pena Janethe, Ghofrani H Ardeschir, Humbert Marc
Hannover Medical School and the German Center for Lung Research, Hannover, Germany
George Washington University, Washington, DC, USA.
Eur Respir J. 2025 May 6;65(5). doi: 10.1183/13993003.01424-2024. Print 2025 May.
Pulmonary arterial hypertension is a progressive disease associated with significant morbidity and mortality. Sotatercept is a first-in-class activin signalling inhibitor that acts to restore the balance between the growth-promoting and growth-inhibiting signalling pathways.
This , exploratory, pooled analysis combines data from the double-blind placebo periods of the phase 2 PULSAR (NCT03496207) and phase 3 STELLAR (NCT04576988) studies. Both studies were international, multicentre, randomised, double-blind, placebo-controlled trials in patients with pulmonary arterial hypertension. Efficacy and safety parameters common to both studies were analysed.
A total of 429 patients were randomised and treated; 237 received sotatercept and 192 received placebo. Adding sotatercept to background pulmonary arterial hypertension therapy for 24 weeks improved exercise capacity (as assessed by 6-min walk distance), pulmonary vascular resistance and World Health Organization functional class, and delayed time to first occurrence of death or clinical worsening event. There were clinically important reductions in both pulmonary and right heart pressures; improvements in right ventricle size during both systole and diastole; and enhancements in right ventricle contractility and right ventricular-pulmonary artery coupling. The number of patients who experienced at least one adverse event of interest or special interest (increased haemoglobin, thrombocytopenia, bleeding events (mostly epistaxis), increased blood pressure and telangiectasia) was higher in the sotatercept group than the placebo group.
This pooled analysis confirms that sotatercept delivers therapeutic benefit across a range of efficacy end-points and has favourable safety in patients with pulmonary arterial hypertension. Increased duration of follow-up will provide further insight into long-term outcomes of sotatercept in patients with pulmonary arterial hypertension.
肺动脉高压是一种与高发病率和死亡率相关的进行性疾病。索他西普是一种一流的激活素信号抑制剂，其作用是恢复促生长信号通路和生长抑制信号通路之间的平衡。
这项探索性汇总分析结合了2期PULSAR（NCT03496207）和3期STELLAR（NCT04576988）研究双盲安慰剂期的数据。两项研究均为针对肺动脉高压患者的国际多中心随机双盲安慰剂对照试验。对两项研究共有的疗效和安全性参数进行了分析。
共有429例患者被随机分组并接受治疗；237例接受索他西普治疗，192例接受安慰剂治疗。在背景肺动脉高压治疗基础上加用索他西普治疗24周可改善运动能力（通过6分钟步行距离评估）、肺血管阻力和世界卫生组织功能分级，并延迟首次发生死亡或临床恶化事件的时间。肺压和右心压力均有具有临床意义的降低；收缩期和舒张期右心室大小均有改善；右心室收缩力和右心室-肺动脉耦合增强。索他西普组经历至少一项关注不良事件或特殊关注不良事件（血红蛋白升高、血小板减少、出血事件（主要是鼻出血）、血压升高和毛细血管扩张）的患者数量高于安慰剂组。
这项汇总分析证实，索他西普在一系列疗效终点上均具有治疗益处，并且在肺动脉高压患者中具有良好的安全性。延长随访时间将进一步深入了解索他西普在肺动脉高压患者中的长期疗效。
