N Engl J Med
ERS 2025: Sotatercept reduces early clinical worsening in PAH
October 2, 2025

Early initiation of sotatercept in pulmonary arterial hypertension (PAH) substantially lowers the risk of clinical worsening, with rapid onset of benefit and a favorable safety profile, according to results shared at the European Respiratory Society meeting. These findings support sotatercept as a disease-modifying therapy for newly diagnosed, intermediate/high-risk PAH patients, complementing existing background regimens.
Study details: The phase 3, randomized, double-blind HYPERION trial (NCT04811092) enrolled 320 adults with WHO functional class II/III PAH diagnosed within the prior year, at intermediate or high risk of death, and receiving double or triple background therapy. Participants were randomized to SC sotatercept (starting dose 0.3 mg/kg, titrated to 0.7 mg/kg every 21 days) or placebo. Primary endpoint: time to first clinical worsening event (composite of death, unplanned PAH hospitalization, atrial septostomy, lung transplantation, or exercise test deterioration).
Results: The trial was stopped early due to loss of equipoise after positive interim data. Over a median 13.2 months, primary endpoint events occurred in 11% of sotatercept-treated patients vs. 37% with placebo (hazard ratio 0.24; 95% confidence interval, 0.14–0.41; P<0.001). Benefit was consistent across prespecified subgroups. Most events were driven by reduced exercise test deterioration and fewer PAH hospitalizations. Adverse events included epistaxis (31.9%) and telangiectasia (26.2%).
Source:
McLaughlin VV, et al; HYPERION Trial Investigators. (2025, September 30). N Engl J Med. Sotatercept for Pulmonary Arterial Hypertension within the First Year after Diagnosis. https://pubmed.ncbi.nlm.nih.gov/41025556/
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