The phase 3 HYPERION trial on sotatercept enrolled 320 adults with newly diagnosed pulmonary arterial hypertension (within 1 year of diagnosis) at intermediate or high risk who were already on double or triple background therapy. Patients were randomized to receive add-on subcutaneous sotatercept or placebo every 21 days.
The trial stopped early due to compelling efficacy. After a median 13.2 months follow-up, clinical worsening occurred in only 10.6% of sotatercept patients compared to 36.9% on placebo—a 76% risk reduction (HR: 0.24, p<0.001). The benefit was driven primarily by preventing exercise deterioration (5.0% vs. 28.8%) and reducing hospitalizations for PAH worsening (1.9% vs. 8.8%). Deaths were similar between groups (4.4% vs. 3.8%).
The most common adverse events with sotatercept were epistaxis (nosebleeds, 32%) and telangiectasia (26%).
The study demonstrates that adding sotatercept early in the disease course significantly reduces clinical worsening in pulmonary arterial hypertension patients already on aggressive background therapy.
Read more at this link on the New England Journal of Medicine
Citation
Sotatercept for Pulmonary Arterial Hypertension within the First Year after Diagnosis, Vallerie V. McLaughlin, M.D., Marius M. Hoeper, M.D., Ph.D., David B. Badesch, M.D., H. Ardeschir Ghofrani, M.D., J. Simon R. Gibbs, M.D., Mardi Gomberg-Maitland, M.D., Ioana R. Preston, M.D., Rogerio Souza, M.D., Ph.D., Aaron B. Waxman, M.D., Ph.D., Grzegorz Kopeć, M.D., Ph.D., Gisela Meyer, M.D., Karen M. Olsson, M.D., Wei Fu, Ph.D., Yaru Shi, Ph.D., Barry Miller, M.S., Samuel S. Kim, Ph.D., Harald S. Mackenzie, M.B., Ch.B., Michela Brambatti, M.D., Mahesh J. Patel, M.D., Joerg Koglin, M.D., Ph.D., Alexandra G. Cornell, M.D., M.C.R., and Marc Humbert, M.D., Ph.D., for the HYPERION Trial Investigators Published, September 30, 2025 DOI: 10.1056/NEJMoa2508170