Marius M. Hoeper, David B. Badesch, H. Ardeschir Ghofrani, J. Simon R. Gibbs, Mardi Gomberg-Maitland, Valerie V. McLaughlin, Ioana R. Preston, Rogerio Souza, Aaron B. Waxman, Ekkehard Grünig, Grzegorz Kopeć, Gisela Meyer, Karen M. Olsson, Stephan Rosenkranz, Yayun Xu, Barry Miller, Marcie Fowler, John Butler, Jeorg Koglin, Janethe de Oliveira Pena, and Marc Humbert, for the STELLAR Trial Investigators
Hannover Medical School. Universities of Giessen and Marburg Lung Center. Thoraxklinik-Heidelberg. University Hospital Cologne. University of Colorado, Anschutz Medical Campus. Imperial College London. George Washington University. University of Michigan. Tufts Medical Center. Brigham and Women’s Hospital. Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo. Irmandade da Santa Casa de Misericórdia de Porto Alegre. Jagiellonian University Medical College, John Paul II Hospital in Krakow. Merck and Acceleron Pharma. Université Paris-Saclay and Hôpital Bicêtre (Assistance Publique-Hôpitaux de Paris).
Germany, United States, United Kingdom, Brazil, Poland and France
New England Journal of Medicine
New Eng J Med 2023; 388: 1478-1490
DOI: 10.1056/NEJMoa2213558
Abstract
Background: Pulmonary arterial hypertension is a progressive disease involving proliferative remodeling of the pulmonary vessels. Despite therapeutic advances, the disease-associated morbidity and mortality remain high. Sotatercept is a fusion protein that traps activins and growth differentiation factors involved in pulmonary arterial hypertension.
Methods: We conducted a multicenter, double-blind, phase 3 trial in which adults with pulmonary arterial hypertension (World Health Organization [WHO] functional class II or III) who were receiving stable background therapy were randomly assigned in a 1:1 ratio to receive subcutaneous sotatercept (starting dose, 0.3 mg per kilogram of body weight; target dose, 0.7 mg per kilogram) or placebo every 3 weeks. The primary end point was the change from baseline at week 24 in the 6-minute walk distance. Nine secondary end points, tested hierarchically in the following order, were multicomponent improvement, change in pulmonary vascular resistance, change in N-terminal pro-B-type natriuretic peptide level, improvement in WHO functional class, time to death or clinical worsening, French risk score, and changes in the Pulmonary Arterial Hypertension-Symptoms and Impact (PAH-SYMPACT) Physical Impacts, Cardiopulmonary Symptoms, and Cognitive/Emotional Impacts domain scores; all were assessed at week 24 except time to death or clinical worsening, which was assessed when the last patient completed the week 24 visit.
Results: A total of 163 patients were assigned to receive sotatercept and 160 to receive placebo. The median change from baseline at week 24 in the 6-minute walk distance was 34.4 m (95% confidence interval [CI], 33.0 to 35.5) in the sotatercept group and 1.0 m (95% CI, -0.3 to 3.5) in the placebo group. The Hodges-Lehmann estimate of the difference between the sotatercept and placebo groups in the change from baseline at week 24 in the 6-minute walk distance was 40.8 m (95% CI, 27.5 to 54.1; P<0.001). The first eight secondary end points were significantly improved with sotatercept as compared with placebo, whereas the PAH-SYMPACT Cognitive/Emotional Impacts domain score was not. Adverse events that occurred more frequently with sotatercept than with placebo included epistaxis, dizziness, telangiectasia, increased hemoglobin levels, thrombocytopenia, and increased blood pressure.
Conclusions: In patients with pulmonary arterial hypertension who were receiving stable background therapy, sotatercept resulted in a greater improvement in exercise capacity (as assessed by the 6-minute walk test) than placebo. (Funded by Acceleron Pharma, a subsidiary of MSD; STELLAR ClinicalTrials.gov number, NCT04576988.).
Category
Medical Therapy. Efficacy or Lack of Efficacy
Medical Therapy. Adverse Effects or Lack of Adverse Effects
Age Focus: Adult Pulmonary Vascular Disease
Fresh or Filed Publication: Filed (PHiled). Greater than 1-2 years since publication
Article Access
Free PDF File or Full Text Article Available Through PubMed or DOI: Yes