N Engl J Med

ACC 2025: Sotatercept significantly reduces adverse outcomes in high-risk PAH

April 2, 2025

In high-risk adults with pulmonary arterial hypertension (PAH) on maximum tolerated background therapy, sotatercept treatment reduced the risk of death, lung transplantation, or hospitalization (≥24 hours) for worsening PAH compared with placebo. The results were shared at American College of Cardiology (ACC).25.

Study details: The ZENITH trial (NCT04896008) was a phase 3, multicenter, double-blind, placebo-controlled study involving 172 adults with WHO functional class III or IV PAH at high risk of death. Participants were randomized to receive either standard care plus SC sotatercept or placebo. The trial ran from December 2021 to July 2024. The primary end point was a composite of death from any cause, lung transplantation, or hospitalization (≥24 hours) for worsening pulmonary arterial hypertension.

Results: Sotatercept significantly reduced the composite outcome of death from any cause, lung transplantation, or hospitalization for worsening PAH by 76% compared with placebo (hazard ratio [HR], 0.24; p<0.001). Specifically, 17.4% of patients in the sotatercept group reached the primary endpoint vs. 54.7% in the placebo group. The most common adverse events in the sotatercept group were epistaxis and telangiectasia.

Sources:

(2025, March 31). NIH. ZENITH: Sotatercept Effectively Reduces Composite Outcome in High-Risk PAH. [News release]. https://www.acc.org/Latest-in-Cardiology/Journal-Scans/2025/03/24/16/30/mon-9am-zenith-acc-2025

Humbert M, et al; ZENITH Trial Investigators. (2025, March 31). N Engl J Med. Sotatercept in Patients with Pulmonary Arterial Hypertension at High Risk for Death. https://pubmed.ncbi.nlm.nih.gov/40167274/