Pulmonary hypertension · Activin signalling inhibition
Sotatercept for Pulmonary Arterial Hypertension within the First Year after Diagnosis
| Design | Phase 3, randomised, double-blind, placebo-controlled trial, stopped early |
|---|---|
| Treatment | Sotatercept added to background therapy |
| Control | Placebo added to background therapy |
| Population | 320 adults diagnosed with pulmonary arterial hypertension less than one year earlier |
| Follow-up | Median 13.2 months |
| Primary endpoint | Time to first clinical worsening event |
| Result | At least one primary endpoint event occurred in 17 of 160 (10.6%) on sotatercept versus 59 of 160 (36.9%) on placebo — hazard ratio 0.24 (95% CI 0.14 to 0.41, p<0.001) over a median 13.2 months. The trial was stopped early after positive results from earlier sotatercept trials removed equipoise. |
| Secondary endpoints | Six-minute walk distance, WHO functional class, NT-proBNP |
Among adults with pulmonary arterial hypertension who had received the diagnosis less than 1 year earlier, the addition of sotatercept to background therapy resulted in a lower risk of clinical worsening than placebo.
The trial authors, in the published abstract
Extends ZENITH from high-risk established disease to newly diagnosed patients, pushing sotatercept earlier in the treatment sequence alongside the upfront dual therapy of AMBITION. Stopped early for loss of equipoise rather than for efficacy — an honest reason, but it leaves the effect size less precisely estimated.
McLaughlin VV, Hoeper MM, Badesch DB, et al. Sotatercept for Pulmonary Arterial Hypertension within the First Year after Diagnosis. N Engl J Med 2025 Oct 23;393(16):1599-1611.