Efficacy and safety of the activin signalling inhibitor, sotatercept, in a pooled analysis of PULSAR and STELLAR studies

Marius M. Hoeper, Hannover Medical School and the German Center for Lung Research, Hannover, Germany hoeper.marius@mh-hannover.de.
Mardi Gomberg-Maitland, George Washington University, Washington, DC, USA.
David B. Badesch, University of Colorado, Anschutz Medical Campus, Aurora, CO, USA.
J Simon Gibbs, National Heart and Lung Institute, Imperial College London, London, UK.
Ekkehard Grünig, Thoraxklinik-Heidelberg and the German Center for Lung Research, Heidelberg, Germany.
Grzegorz Kopeć, The Pulmonary Circulation Center, Department of Cardiac and Vascular Diseases, Jagiellonian University Medical College, St. John Paul II Hospital in Krakow, Krakow, Poland.
Vallerie V. McLaughlin, University of Michigan, Ann Arbor, MI, USA.
Gisela Meyer, Irmandade da Santa Casa de Misericórdia de Porto Alegre, Porto Alegre, Brazil.
Karen M. Olsson, Hannover Medical School and the German Center for Lung Research, Hannover, Germany.
Ioana R. Preston, Tufts Medical Center, Boston, MA, USA.
Stephan Rosenkranz, Department of Cardiology, Heart Center, University Hospital Cologne, and Cologne Cardiovascular Research Center (CCRC), Medical Faculty, University of Cologne, Cologne, Germany.
Rogerio Souza, Instituto do Coração, Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo, Sao Paulo, Brazil.
Aaron B. Waxman, Brigham and Woman's Hospital, Boston, MA, USA.
Loïc Perchenet, Merck & Co., Inc., Rahway, NJ, USA.
James Strait, Merck & Co., Inc., Rahway, NJ, USA.
Aiwen Xing, Merck & Co., Inc., Rahway, NJ, USA.
Solaiappan Manimaran, Merck & Co., Inc., Rahway, NJ, USA.
Xuelong Wang, Merck & Co., Inc., Rahway, NJ, USA.
Barry Miller, Merck & Co., Inc., Rahway, NJ, USA.
Alexandra G. Cornell, Merck & Co., Inc., Rahway, NJ, USA.
Janethe de Oliveira Pena, Merck & Co., Inc., Rahway, NJ, USA.
H Ardeschir Ghofrani, Department of Internal Medicine, Justus-Liebig-University Giessen, Universities of Giessen and Marburg Lung Center (UGMLC), Member of the German Center for Lung Research (DZL), Giessen, Germany.
Marc Humbert, Université Paris-Saclay, INSERM Unité Mixte de Recherche en Santé 999 (HPPIT), Service de Pneumologie et Soins Intensifs Respiratoires, Hôpital Bicêtre (Assistance Publique-Hôpitaux de Paris), Le Kremlin-Bicêtre, France.

Document Type

Journal Article

Publication Date

1-30-2025

Journal

The European respiratory journal

DOI

10.1183/13993003.01424-2024

Abstract

INTRODUCTION: Pulmonary arterial hypertension (PAH) is a progressive disease associated with significant morbidity and mortality. Sotatercept is a first-in-class activin signalling inhibitor that acts to restore the balance between the growth-promoting and growth-inhibiting signalling pathways. METHODS: This post-hoc, exploratory, pooled analysis combines data from the double-blind placebo periods of the phase 2 PULSAR (NCT03496207) and phase 3 STELLAR (NCT04576988) studies. Both studies were international, multicentre, randomised, double-blind, placebo-controlled trials in patients with PAH. Efficacy and safety parameters common to both studies were analysed. RESULTS: A total of 429 patients were randomised and treated; 237 received sotatercept and 192 received placebo. Adding sotatercept to background PAH therapy for 24 weeks improved exercise capacity (as assessed by 6-min walk distance), pulmonary vascular resistance, World Health Organization functional class, and delayed time to first occurrence of death or clinical worsening event. There were clinically important reductions in both pulmonary and right heart pressures; improvements in right ventricle (RV) size during both systole and diastole; and enhancements in RV contractility and RV-pulmonary artery coupling. The number of patients who experienced at least one adverse event of interest or special interest (increased haemoglobin, thrombocytopenia, bleeding events [mostly epistaxis], increased blood pressure, and telangiectasia) was higher in the sotatercept group than the placebo group. DISCUSSION: This pooled analysis confirms that sotatercept delivers therapeutic benefit across a range of efficacy endpoints and has favourable safety in patients with PAH. Increased duration of follow-up will provide further insight into long-term outcomes of sotatercept in patients with PAH.

Department

Medicine

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