Effect of sotatercept on circulating proteomics in pulmonary arterial hypertension

Alterations in specific signaling pathways within the BMP/TGF-β family, involving several finely regulated activator or inhibitor ligands, have been identified as pathogenic drivers of pulmonary arterial hypertension (PAH). These alterations, particularly affecting BMPRII and activin-dependent pathways, have led to innovative therapies, notably the development of sotatercept [1, 2]. Sotatercept, a fusion protein of the extracellular domain of human ACTRIIA and the Fc domain of human IgG1, has shown promising results in improving key clinical, functional, and hemodynamic parameters in PAH patients, as evidenced by positive results in the phase-2 PULSAR and phase-3 STELLAR trials [3, 4]. Footnotes This manuscript has recently been accepted for publication in the European Respiratory Journal . It is published here in its accepted form prior to copyediting and typesetting by our production team. After these production processes are complete and the authors have approved the resulting proofs, the article will move to the latest issue of the ERJ online. Please open or download the PDF to view this article. Conflict of interest: S. Bodduluri has nothing to disclose. Conflict of interest: Over the last three years, L.Savale reports personal fees from Bayer, MSD, Janssen and grants from Acceleron, Janssen, MSD, outside the submitted work. Conflict of interest: L. Tu has nothing to disclose. Conflict of interest: C.Normand has no conflict of interest to declare. Conflict of interest: A.Boucly reports honoraria for speaking and scientific advisory boards from AOP Orphan, Acceleron, AstraZeneca, Ferrer, Janssen and Merck. Conflict of interest: O.Sitbon reports grants from Aerovate, AOP Orphan, Ferrer, Janssen (formerly Actelion) and MSD, consultancy fees from MSD, Enzyvant, AOP Orphan, Ferrer, Gossamer Bio, Janssen, Liquidia and Respira Therapeutics, payment or honoraria for lectures, presentations, manuscript writing or educational events from AOP Orphan, Bayer Janssen, Ferrer, United Therapeutics and MSD, participation on a data safety monitoring board or advisory board with Bayer, Enzyvant, Gossamer Bio, Janssen, United Therapeutics and MSD, Conflict of interest: D. Montani reports grants from Acceleron, Janssen and Merck MSD, consultancy fees from Acceleron, Merck MSD, Janssen, and Ferrer, and payment or honoraria for lectures, presentations, manuscript writing or educational events from Bayer, Janssen, Boehringer Ingelheim, Chiesi, GSK, Ferrer, and Merck MSD. Conflict of interest: K.Olsson reports honoraria for speaking, steering committees, scientific advisory boards from Acceleron, Actelion, AOP Health, Bayer, Ferrer, Janssen, and MSD. Conflict of interest: DH Park is supported by Program of Hannover Medical School for Clinician Scientists (PRACTIS), funded by the Deutsche Forschungsgemeinschaft (DFG, ME 3696/3-1) and the German Center for Lung Research (DZL). Conflict of interest: J.Fuge has received fees for lectures and/or consultations for AstraZeneca, outside the present work. Conflict of interest: JC Kamp is supported by PRACTIS – Clinician Scientist Program at Hannover Medical School, funded by the German Research Foundation (DGF, ME 3696/3-1). Conflict of interest: M.Humbert reports grants and personal fees from 35 Pharma, Acceleron, Aerovate, Altavant, AOP Orphan, Bayer, Chiesi, Ferrer, Gossamer, Janssen, Keros, Liquidia, Merck, MorphogenIX, Respira and United Therapeutics, outside the submitted work. Conflict of interest: M.Hoeper reports honoraria for speaking, steering committees, scientific advisory boards from Acceleron, Actelion, AOP Health, Bayer, Ferrer, Gossamer Bio, Janssen, Keros, MSD. Conflict of interest: C.Guignabert reports grants from Acceleron, Corteria, Structure therapeutics (ex ShouTi), and Janssen, grants and personal fees from Merck, outside the submitted work, and patents planned, issued or pending (WO/2024/023139, WO/2018/011376).