Efficacy and safety of the activin signalling inhibitor, sotatercept, in a pooled analysis of PULSAR and STELLAR studies.

Sotatercept is a first-in-class activin signalling inhibitor that acts to restore the balance between the growth-promoting and growth-inhibiting signalling pathways.

Sotatercept 是一种首创的 activin 信号通路抑制剂，其作用是恢复促进生长和抑制生长的信号通路之间的平衡。

Methods

This post hoc, exploratory, pooled analysis combines data from the double-blindplacebo periods of the phase 2 PULSAR (NCT03496207) and phase 3 STELLAR (NCT04576988) studies.

这项事后、探索性的汇总分析结合了第二阶段PULSAR (NCT03496207)和第三阶段STELLAR (NCT04576988)研究的双盲安慰剂期间的数据。

Both studies were international, multicentre, randomised, double-blind, placebo-controlledtrials in patients with pulmonary arterial hypertension.

这两项研究都是国际性的、多中心的、随机的、双盲的、安慰剂对照试验，针对的是肺动脉高压患者。

Efficacy and safety parameters common to both studies were analysed.

两项研究均分析了疗效和安全性的一般参数。

Results

A total of 429 patients were randomised and treated; 237 received sotatercept and 192 received placebo.

共有429名患者被随机分配接受治疗；其中237名患者接受了sotatercept治疗，192名患者接受了安慰剂。

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.

将索塔特瑞普添加到背景肺动脉高压治疗中24周，改善了运动能力（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等级，并延迟了首次死亡或临床恶化事件的时间。

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.

在肺部和右心压力方面都有临床上重要的降低；在收缩期和舒张期右心室大小都有所改善；并且增强了右心室收缩力和右心室-肺动脉耦合。

The number of patients who experienced at least one adverse eventof 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.

经历至少一次感兴趣或特别关注的不良事件（血红蛋白增加、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）的患者数量在sotatercept组比安慰剂组更高。

Conclusions

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.

这项汇总分析证实，sotatercept在一系列疗效终点上为肺动脉高压患者提供了治疗益处，并且具有良好的安全性。

Increased duration of follow-up will provide further insight into long-term outcomes of sotatercept in patients with pulmonary arterial hypertension.

延长随访时间将为肺动脉高压患者使用sotatercept的长期结果提供更深入的见解。