Sotatercept in Patients with Pulmonary Arterial Hypertension at High Risk for Death

Authors

Marc Humbert, Université Paris-Saclay, INSERM Unité Mixte de Recherche en Santé 999, Hypertension Pulmonaire, Physiopathologie et Innovation Thérapeutique, Service de Pneumologie et Soins Intensifs Respiratoires, Hôpital Bicêtre (Assistance Publique-Hôpitaux de Paris), European Reference Network for Rare Respiratory Diseases, Le Kremlin-Bicêtre, France.
Vallerie V. McLaughlin, Department of Internal Medicine, Division of Cardiovascular Medicine, University of Michigan, Ann Arbor.
David B. Badesch, Pulmonary Hypertension Program, University of Colorado, Anschutz Medical Campus, Aurora.
H Ardeschir Ghofrani, Department of Internal Medicine, Justus-Liebig University Giessen, Universities of Giessen and Marburg Lung Center and Institute for Lung Health, Members of the German Center for Lung Research, Giessen, Germany.
J Simon Gibbs, National Heart and Lung Institute, Imperial College London, London.
Mardi Gomberg-Maitland, Division of Cardiovascular Medicine, George Washington University School of Medicine and Health Sciences, Washington, DC.
Ioana R. Preston, Pulmonary and Critical Care Medicine, Lahey Hospital and Medical Center, Burlington, MA.
Rogerio Souza, Divisão de Pneumologia, Instituto do Coração, Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo, São Paulo.
Aaron B. Waxman, Pulmonary and Critical Care Medicine, Brigham and Woman's Hospital, Harvard Medical School, Boston.
Victor M. Moles, Department of Internal Medicine, Division of Cardiovascular Medicine, University of Michigan, Ann Arbor.
Laurent Savale, Université Paris-Saclay, INSERM Unité Mixte de Recherche en Santé 999, Hypertension Pulmonaire, Physiopathologie et Innovation Thérapeutique, Service de Pneumologie et Soins Intensifs Respiratoires, Hôpital Bicêtre (Assistance Publique-Hôpitaux de Paris), European Reference Network for Rare Respiratory Diseases, Le Kremlin-Bicêtre, France.
Carmine Dario Vizza, Department of Clinical Internal, Anesthesiologic, and Cardiovascular Science, Sapienza University of Rome, Rome.
Stephan Rosenkranz, Department of Cardiology, and Cologne Cardiovascular Research Center, Medical Faculty, Heart Center, University Hospital Cologne, Cologne, Germany.
Yaru Shi, Merck, Rahway, NJ.
Barry Miller, Merck, Rahway, NJ.
Harald S. Mackenzie, Merck, Rahway, NJ.
Samuel S. Kim, Merck, Rahway, NJ.
Maria José Loureiro, Merck, Rahway, NJ.
Mahesh J. Patel, Merck, Rahway, NJ.
Joerg Koglin, Merck, Rahway, NJ.
Alexandra G. Cornell, Merck, Rahway, NJ.
Marius M. Hoeper, Department of Respiratory Medicine and Infectious Diseases, Hannover Medical School and Member of the German Center for Lung Research, Biomedical Research in End-Stage and Obstructive Lung Disease Hannover, Hannover, Germany.

Document Type

Journal Article

Publication Date

3-31-2025

Journal

The New England journal of medicine

DOI

10.1056/NEJMoa2415160

Abstract

BACKGROUND: Sotatercept improves exercise capacity and delays the time to clinical worsening in patients with World Health Organization (WHO) functional class II or III pulmonary arterial hypertension. The effects of add-on sotatercept in patients with advanced pulmonary arterial hypertension and a high risk of death are unclear. METHODS: In this phase 3 trial, we randomly assigned patients with pulmonary arterial hypertension (WHO functional class III or IV) and a high 1-year risk of death (Registry to Evaluate Early and Long-Term Pulmonary Arterial Hypertension Disease Management Lite 2 risk score, ≥9) who were receiving the maximum tolerated dose of background therapy to receive add-on sotatercept (starting dose, 0.3 mg per kilogram of body weight; escalated to target dose, 0.7 mg per kilogram) or placebo every 3 weeks. The primary end point was a composite of death from any cause, lung transplantation, or hospitalization (≥24 hours) for worsening pulmonary arterial hypertension, assessed in a time-to-first-event analysis. RESULTS: A total of 172 patients were included (86 each in the sotatercept and placebo groups). The trial was stopped early on the basis of the efficacy results of a prespecified interim analysis. At least one primary end-point event occurred in 15 patients (17.4%) in the sotatercept group and in 47 patients (54.7%) in the placebo group (hazard ratio, 0.24; 95% confidence interval, 0.13 to 0.43; P<0.001). Death from any cause occurred in 7 patients (8.1%) in the sotatercept group and in 13 patients (15.1%) in the placebo group; lung transplantation in 1 patient (1.2%) and 6 patients (7.0%), respectively; and hospitalization for worsening pulmonary arterial hypertension in 8 patients (9.3%) and 43 patients (50.0%). The most common adverse events with sotatercept were epistaxis and telangiectasia. CONCLUSIONS: 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. (Funded by Merck Sharp and Dohme, a subsidiary of Merck [Rahway, NJ]; ZENITH ClinicalTrials.gov number, NCT04896008.).

APA Citation

Humbert, Marc; McLaughlin, Vallerie V.; Badesch, David B.; Ghofrani, H Ardeschir; Gibbs, J Simon; Gomberg-Maitland, Mardi; Preston, Ioana R.; Souza, Rogerio; Waxman, Aaron B.; Moles, Victor M.; Savale, Laurent; Vizza, Carmine Dario; Rosenkranz, Stephan; Shi, Yaru; Miller, Barry; Mackenzie, Harald S.; Kim, Samuel S.; Loureiro, Maria José; Patel, Mahesh J.; Koglin, Joerg; Cornell, Alexandra G.; and Hoeper, Marius M., "Sotatercept in Patients with Pulmonary Arterial Hypertension at High Risk for Death" (2025). GW Authored Works. Paper 6732.
https://hsrc.himmelfarb.gwu.edu/gwhpubs/6732

Department

Medicine