Marc Humbert, Vallerie McLaughlin, J. Simon R. Gibbs, Mardi Gomberg-Maitland, Marius M. Hoeper, Ioana R. Preston, Rogerio Souza, Aaron B. Waxman, Hossein-Ardeschir Ghofrani, Pilar Escribano Subias1, Jeremy Feldman, Gisela Meyer, David Montani, Karen M. Olsson, Solaiappan Manimaran, Janethe de Oliveira Pena, David B. Badesch
Hôpital Bicêtre, Assistance Publique-Hôpitaux de Paris. University of Michigan Health System. Imperial College Healthcare NHS Trust. George Washington University School of Medicine and Health Sciences. Hannover Medical School. Tufts Medical Center. University of São Paulo Medical School. Brigham and Women’s Hospital and Harvard Medical School, Boston. University of Giessen and Marburg. Universidad Complutense. Arizona Pulmonary Specialists. Complexo Hospitalar Santa Casa de Porto Alegre. Acceleron Pharma Inc. University of Colorado.
France, United States, United Kingdom, Germany, Brazil and Spain
European Respiratory Journal
Eur Respir J 2023; 61: 2201347
DOI: 10.1183/13993003.01347-2022
Abstract
Background: In participants with pulmonary arterial hypertension, 24 weeks of sotatercept resulted in a significantly greater reduction from baseline in pulmonary vascular resistance than placebo. This report characterises the longer-term safety and efficacy of sotatercept in the PULSAR open-label extension. We report cumulative safety, and efficacy at months 18-24, for all participants treated with sotatercept.
Methods: PULSAR was a phase 2, randomised, double-blind, placebo-controlled study followed by an open-label extension, which evaluated sotatercept on top of background pulmonary arterial hypertension therapy in adults. Participants originally randomised to placebo were re-randomised 1:1 to sotatercept 0.3 or 0.7 mg·kg-1 (placebo-crossed group); those initially randomised to sotatercept continued the same sotatercept dose (continued-sotatercept group). Safety was evaluated in all participants who received ≥1 dose of sotatercept. The primary efficacy endpoint was change from baseline to months 18-24 in pulmonary vascular resistance. Secondary endpoints included 6-min walk distance and functional class. Two prespecified analyses, placebo-crossed and delayed-start, evaluated efficacy irrespective of dose.
Results: Of 106 participants enrolled in the PULSAR study, 97 continued into the extension period. Serious treatment-emergent adverse events were reported in 32 (30.8%) participants; 10 (9.6%) reported treatment-emergent adverse events leading to study discontinuation. Three (2.9%) participants died, none considered related to study drug. The placebo-crossed group demonstrated significant improvement across primary and secondary endpoints and clinical efficacy was maintained in the continued-sotatercept group.
Conclusion: These results support the longer-term safety and durability of clinical benefit of sotatercept for pulmonary arterial hypertension.
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