Pulmonary hypertension · Activin signalling inhibition
Sotatercept in Patients with Pulmonary Arterial Hypertension at High Risk
| Design | Randomised, double-blind, placebo-controlled trial, stopped early for efficacy |
|---|---|
| Treatment | Sotatercept added to maximum tolerated background therapy |
| Control | Placebo added to maximum tolerated background therapy |
| Population | 172 high-risk adults with pulmonary arterial hypertension in WHO functional class III or IV |
| Follow-up | Event-driven; stopped early at a prespecified interim analysis |
| Primary endpoint | Composite of death from any cause, lung transplantation, or hospitalisation of at least 24 hours for worsening PAH |
| Result | At least one primary endpoint event occurred in 15 of 86 (17.4%) on sotatercept versus 47 of 86 (54.7%) on placebo — hazard ratio 0.24 (95% CI 0.13 to 0.43, p<0.001). Death from any cause occurred in 7 (8.1%) versus 13 (15.1%). |
| Secondary endpoints | All-cause death, lung transplantation, hospitalisation for worsening PAH |
Among high-risk adults with pulmonary arterial hypertension who were receiving the maximum tolerated dose of background therapy, treatment with sotatercept resulted in a lower risk of a composite of death from any cause, lung transplantation, or hospitalization (≥24 hours) for worsening pulmonary arterial hypertension than placebo.
The trial authors, in the published abstract
An effect size rarely seen in pulmonary hypertension, in the sickest patients, on top of maximal existing therapy — and the trial was stopped early for it. Sotatercept targets a different pathway from the vasodilators of AMBITION, acting on the proliferative remodelling rather than the vascular tone.
Humbert M, McLaughlin VV, Badesch DB, et al. Sotatercept in Patients with Pulmonary Arterial Hypertension at High Risk for Death. N Engl J Med 2025 May 29;392(20):1987-2000.