Effects of sotatercept on haemodynamics and right heart function: analysis of the STELLAR trial

Rogerio Souza, Instituto do Coração, Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo, Sao Paulo, Brazil.
David B. Badesch, University of Colorado, Anschutz Medical Campus, Aurora, CO, 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.
J Simon Gibbs, National Heart and Lung Institute, Imperial College London, London, UK.
Mardi Gomberg-Maitland, George Washington University, Washington, DC, USA.
Vallerie V. McLaughlin, University of Michigan, Ann Arbor, MI, USA.
Ioana R. Preston, Tufts Medical Center, Boston, MA, USA.
Aaron B. Waxman, Brigham and Woman's Hospital, Boston, MA, USA.
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, John Paul II Hospital in Krakow, Krakow, Poland.
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.
Stephan Rosenkranz, Department of Cardiology, and Cologne Cardiovascular Research Center (CCRC), Heart Center, University Hospital Cologne, Cologne, Germany.
Jianxin Lin, Merck & Co., Inc., Rahway, NJ, USA.
Amy O. Johnson-Levonas, Merck & Co., Inc., Rahway, NJ, USA.
Janethe de Oliveira Pena, Merck & Co., Inc., Rahway, NJ, USA.
Marc Humbert, Université Paris-Saclay, INSERM Unité Mixte de Recherche en Santé 999, Hôpital Bicêtre (Assistance Publique-Hôpitaux de Paris), Le Kremlin-Bicêtre, France.
Marius M. Hoeper, Hannover Medical School and the German Center for Lung Research, Hannover, Germany hoeper.marius@mh-hannover.de.

Document Type

Journal Article

Publication Date

9-1-2023

Journal

The European respiratory journal

Volume

62

Issue

3

DOI

10.1183/13993003.01107-2023

Abstract

BACKGROUND: In the phase 3 STELLAR trial, sotatercept, an investigational first-in-class activin signalling inhibitor, demonstrated beneficial effects on 6-min walk distance and additional efficacy endpoints in pre-treated participants with pulmonary arterial hypertension (PAH). METHODS: This analysis evaluated data from right heart catheterisation (RHC) and echocardiography (ECHO) obtained from the STELLAR trial. Changes from baseline in RHC and ECHO parameters were assessed at 24 weeks. An analysis of covariance (ANCOVA) model was used to estimate differences in least squares means with treatment and randomisation stratification (mono/double triple therapy; World Health Organization functional class II III) as fixed factors, and baseline value as covariate. RESULTS: Relative to placebo, treatment with sotatercept led to significant (all p<0.0001 except where noted) improvements from baseline in mean pulmonary artery (PA) pressure (-13.9 mmHg), pulmonary vascular resistance (-254.8 dyn·s·cm), mean right atrial pressure (-2.7 mmHg), mixed venous oxygen saturation (3.84%), PA elastance (-0.42 mmHg·mL·beat), PA compliance (0.58 mL·mmHg), cardiac efficiency (0.48 mL·beat·mmHg), right ventricular (RV) work (-0.85 g·m) and RV power (-32.70 mmHg·L·min). ECHO showed improvements in tricuspid annular plane systolic excursion (TAPSE) to systolic pulmonary artery pressure ratio (0.12 mm·mmHg), end-systolic and end-diastolic RV areas (-4.39 cm and -5.31 cm, respectively), tricuspid regurgitation and RV fractional area change (2.04% p<0.050). No significant between-group changes from baseline were seen for TAPSE, heart rate, cardiac output, stroke volume or their indices. CONCLUSION: In pre-treated patients with PAH, sotatercept demonstrated substantial improvements in PA pressures, PA compliance, PA-RV coupling and right heart function.

Department

Medicine

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