Title

Sotatercept for the treatment of pulmonary arterial hypertension: PULSAR open-label extension

Authors

Marc Humbert, Department of Respiratory and Intensive Care Medicine, Hôpital Bicêtre, Assistance Publique-Hôpitaux de Paris, INSERM Unité Mixte de Recherche 999, Université Paris-Saclay, Le Kremlin-Bicêtre, France.
Vallerie McLaughlin, Division of Cardiovascular Medicine, Department of Internal Medicine, University of Michigan Health System, Ann Arbor, MI, USA.
J Simon Gibbs, National Heart and Lung Institute, Imperial College London, and the National Pulmonary Hypertension Service, Hammersmith Hospital, Imperial College Healthcare NHS Trust, London, UK.
Mardi Gomberg-Maitland, Department of Medicine, George Washington University School of Medicine and Health Sciences, Washington, DC, USA.
Marius M. Hoeper, Department of Respiratory Medicine, Hannover Medical School, and the German Center for Lung Research (DZL), Hannover, Germany.
Ioana R. Preston, Division of Pulmonary, Critical Care and Sleep Medicine, Tufts Medical Center, Boston, MA, USA.
Rogerio Souza, Pulmonary Division-Heart Institute, University of São Paulo Medical School, São Paulo, Brazil.
Aaron B. Waxman, Division of Pulmonary and Critical Care Medicine, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
Hossein-Ardeschir Ghofrani, Department of Pneumology, University of Giessen and Marburg, Giessen, Germany.
Pilar Escribano Subias, Department of Cardiology, Centro de Investigación Biomédica en Red en Enfermedades Cardiovasculares, Hospital Universitario 12 de Octubre, Universidad Complutense, Madrid, Spain.
Jeremy Feldman, Arizona Pulmonary Specialists, Phoenix, AZ, USA.
Gisela Meyer, Complexo Hospitalar Santa Casa de Porto Alegre, Pulmonary Vascular Research Institute, Porto Alegre, Brazil.
David Montani, Department of Respiratory and Intensive Care Medicine, Hôpital Bicêtre, Assistance Publique-Hôpitaux de Paris, INSERM Unité Mixte de Recherche 999, Université Paris-Saclay, Le Kremlin-Bicêtre, France.
Karen M. Olsson, Department of Respiratory Medicine, Hannover Medical School, and the German Center for Lung Research (DZL), Hannover, Germany.
Solaiappan Manimaran, Acceleron Pharma Inc., a wholly owned subsidiary of Merck & Co., Inc., Rahway, NJ, USA.
Janethe de Oliveira Pena, Acceleron Pharma Inc., a wholly owned subsidiary of Merck & Co., Inc., Rahway, NJ, USA.
David B. Badesch, Division of Pulmonary Sciences and Critical Care Medicine, and Cardiology, University of Colorado, Anschutz Medical Campus, Aurora, CO, USA David.badesch@cuanschutz.edu.

Document Type

Journal Article

Publication Date

8-30-2022

Journal

The European respiratory journal

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 (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.

Department

Medicine

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