Sotatercept; pulmonary arterial hypertension; pulmonary artery; pulmonary hypertension; vascular remodelling; Cardiology and Cardiovascular Medicine
Abstract :
[en] Pulmonary arterial hypertension (PAH) is a rare disease affecting the small pulmonary vessels, ultimately leading to right ventricular failure and death. Current treatment options target three different pathways (endothelin, nitric oxide/cGMP and prostacyclin pathways). Despite their demonstrated efficacy, these therapies (commonly used in combination) do not cure the disease which is why novel pathways beyond the traditional 'big three' are being developed. Sotatercept is a ligand trap for multiple proteins within the TGF-β superfamily that was recently approved in the US for the treatment of PAH. Unlike currently available therapies, sotatercept has the potential to act as an anti-remodelling agent rather than a vasodilator. The safety and efficacy of subcutaneous (SC) sotatercept have been established in two multicentre, placebo-controlled randomised-controlled trials. The compound has been shown to consistently improve a variety of measurable endpoints, including exercise capacity, haemodynamics, quality of life and delay of clinical worsening. The drug appears to have an acceptable safety profile, although it is associated with an increased risk in developing telangiectasia and biological changes affecting platelet counts and haemoglobin. This study reviews the current evidence on SC sotatercept and provides a Belgian perspective on its place in the future treatment strategy for PAH.
Disciplines :
Cardiovascular & respiratory systems
Author, co-author :
Vachiéry, Jean-Luc; Department of Cardiology, Pulmonary Vascular Diseases and Heart Failure Clinic, Hôpital Universitaire de Bruxelles Erasme, Brussels, Belgium
Belge, Catharina; Clinical Department of Respiratory Diseases, University Hospitals of Leuven and Laboratory of Respiratory Diseases and Thoracic Surgery (BREATHE), Leuven, Belgium ; Department of Chronic Diseases and Metabolism (CHROMETA), KU Leuven - University of Leuven, Leuven, Belgium
Cools, Bjorn; Department of Pediatrics, Pediatric Cardiology, University Hospitals of Leuven, Leuven, Belgium ; Department of Cardiovascular Sciences, University of Leuven, Leuven, Belgium
Demeure, Fabian; Department of Cardiology, Université catholique de Louvain, CHU UCL Namur, Yvoir, Belgium
De Pauw, Michel; Department of Cardiology, Ghent University Hospital, Ghent, Belgium
Dewachter, Céline; Department of Cardiology, Pulmonary Vascular Diseases and Heart Failure Clinic, Hôpital Universitaire de Bruxelles Erasme, Brussels, Belgium
De Wolf, Daniel; Department of Pediatric Cardiology of Ghent, University Hospital, Ghent, Belgium ; Department of Pediatric Cardiology of Brussels, University Hospital, Jette, Belgium
Gabriel, Laurence; Department of Cardiology, Université catholique de Louvain, CHU UCL Namur, Yvoir, Belgium
Godinas, Laurent; Clinical Department of Respiratory Diseases, University Hospitals of Leuven and Laboratory of Respiratory Diseases and Thoracic Surgery (BREATHE), Leuven, Belgium ; Department of Chronic Diseases and Metabolism (CHROMETA), KU Leuven - University of Leuven, Leuven, Belgium
Guiot, Julien ; Université de Liège - ULiège > Département des sciences biomédicales et précliniques
Haine, Steven; Department of Cardiology, Antwerp University, Edegem, Belgium ; Department of Genetics, Pharmacology and Physiopathology of Heart, Blood Vessels and Skeleton, Faculty of Medicine, University of Antwerp, Antwerp, Belgium
Leys, Mathias; Department of Respiratory Medicine, AZ Groeninge, Kortrijk, Belgium
Meysman, Marc; Department of Medicine, Respiratory Division, Universitair Ziekenhuis Brussel, Brussels, Belgium
Ruttens, David; Department of Pulmonary Medicine, Ziekenhuis Oost-Limburg (ZOL), Genk, Belgium ; Faculty of Medicine and Life Science, Hasselt University, Hasselt, Belgium
Vandecasteele, Els; Department of Cardiology, Ghent University Hospital, Ghent, Belgium
Weber, Thierry; Department of Respiratory Disease, Hôpital de la Citadelle, Liège, Belgium
Wirtz, Gil; Department of Respiratory Diseases, Centre Hospitalier de Luxembourg, Luxembourg city, Luxembourg
Delcroix, Marion; Clinical Department of Respiratory Diseases, University Hospitals of Leuven and Laboratory of Respiratory Diseases and Thoracic Surgery (BREATHE), Leuven, Belgium ; Department of Chronic Diseases and Metabolism (CHROMETA), KU Leuven - University of Leuven, Leuven, Belgium
ACP reports speaker and consultant fees from Astra-Zeneca, Pfizer, Vifor, Bayer, Boehringer, and Janssen, outside the submitted work, and all paid to her institution. BC reports speaker fees from Abbvie and Medtronic outside the submitted work, and all paid to his institution. CB reports speaker and consultant fees from Merck/MSD and Johnson and Johnson outside the submitted work, and all paid to her institution. CD reports consultant fees from Janssen and Novartis outside the submitted work, and all paid to institution. DDW reports speaker fees from Janssen outside the submitted work and all pair to his institution. DR reports speaker and consultant fees from Janssen, and MSD outside the submitted work. EV reports speaker fees from Janssen, outside the submitted work, and all paid to her institution. FD reports consultant and speaker fees from MSD, Janssen, Amgen, Astra-Zeneca, Daiichi-Sankyo, Novartis, NovoNordisk, Sanofi, Viatris and Servier outside of the submitted work, and all paid to his institution. GW does not report any conflict of interest. JLV reports consultant and speaker fees from Merck/MSD in the context of the submitted work, and consultant fees from Aerovate, GossamerBio, Insmed, Janssen, Pulmovant and United Therapeutics outside of the submitted work. JG reports speaker and consultant fees from Boehringer Ingelheim, Janssen, SMB, GSK, Roche, AstraZeneca, Aquilon, Volition, Oncoradiomics, and Chiesi out of the submitted work. Non-financial support for meeting attendance from AstraZeneca, Chiesi, MSD, Roche, Boehringer Ingelheim and Janssen. LGa reports speaker fees and consultant fees from Astra-Zeneca, Novartis, MSD, Pfizer, Bayer, Boehringer, RMN outside the submitted work, and all paid to her institution. LGo reports consultant fees from Merck/MSD in the context of the submitted work, consultant and lecture fees from Johnson & Johnson, Biotest and Chiesi outside the submitted work. MD reports speaker and consultant fees from Ferrer, Gossamer, Janssen, and MSD outside the submitted work, and all paid to her institution. MDP reports speaker fees for Janssen, all paid to his institution. ML reports consultant and speaker fees in the context of the submitted work from Merck/MSD and Johnson and Johnson. MM reports speaker and consultant fees from GSK, Astra Zeneca, Boehringer-Ingelheim, Janssen, Novartis and Pfizer outside the context of the submitted work. PH Belgi\u00EB (represented by AD and WVS) receives financial support and fees from MSD Belgium BV, Janssen-Cilag NV (Johnson & Johnson) and Gossamer Bio. SH reports speaker and consultant fees from Barizza, Boston Scientific, Daiichi Sankyo, Janssen Cilag, Novartis Pharma, Roularta Media and Viatris outside the submitted work and all paid to his institution. TW does not report any conflict of interest.
Humbert M, Kovacs G, Hoeper MM, et al.2022 ESC/ERS Guidelines for the diagnosis and treatment of pulmonary hypertension. Eur Heart J. 2022;43(38):3618–3731.(b) Humbert M, Kovacs G, Hoeper MM, et al.2022 ESC/ERS Guidelines for the diagnosis and treatment of pulmonary hypertension. Eur Respir J. 2023;61:2200879. doi: 10.1093/eurheartj/ehac237.
Humbert M, Sitbon O, Guignabert C, et al.Treatment of pulmonary arterial hypertension: recent progress and a look to the future. Lancet Respir Med. 2023;11(9):804–819. doi: 10.1016/S2213-2600(23)00264-3.
Humbert M, Guignabert C, Bonnet S, et al.Pathology and pathobiology of pulmonary hypertension: state of the art and research perspectives. Eur Respir J. 2019;53(1):1801887. doi: 10.1183/13993003.01887-2018.
Guignabert C, Humbert M., Targeting transforming growth factor-beta receptors in pulmonary hypertension. Eur Respir J. 2021;57(2):2002341. doi: 10.1183/13993003.02341-2020.
Guignabert C, Savale L, Boucly A, et al.Serum and pulmonary expression profiles in the activin signaling system in pulmonary arterial hypertension. Circulation. 2023;147(24):1809–1822. doi: 10.1161/CIRCULATIONAHA.122.061501.
Humbert M, McLaughlin V, Gibbs JSR, et al.Sotatercept for the treatment of pulmonary arterial hypertension. N Engl J Med. 2021;384(13):1204–1215. doi: 10.1056/NEJMoa2024277.
Souza R, Badesch DB, Ghofrani HA, et al.Effects of sotatercept on haemodynamics and right heart function: analysis of the STELLAR trial. Eur Respir J. 2023;62(3):2301107. doi: 10.1183/13993003.01107-2023.
Humbert M, McLaughlin V, Gibbs JSR, et al.Sotatercept for the treatment of pulmonary arterial hypertension: PULSAR open-label extension. Eur Respir J. 2023;61(1):2201347. doi: 10.1183/13993003.01347-2022.
Hoeper MM, Badesch DB, Ghofrani HA, et al.Phase 3 trial of sotatercept for treatment of pulmonary arterial hypertension. N Engl J Med. 2023;388(16):1478–1490. doi: 10.1056/NEJMoa2213558.
Boucly A, Weatherald J, Savale L, et al.Risk assessment, prognosis and guideline implementation in pulmonary arterial hypertension. Eur Respir J. 2017;50(2):1700889. doi: 10.1183/13993003.00889-2017.
Hoeper MM, Pausch C, Olsson KM, et al.COMPERA 2.0: a refined four-stratum risk assessment model for pulmonary arterial hypertension. Eur Respir J. 2022;60(1):2102311. doi: 10.1183/13993003.02311-2021.
Boucly A, Weatherald J, Savale L, et al.External validation of a refined four-stratum risk assessment score from the French Pulmonary Hypertension Registry. Eur Respir J. 2022;59(6):2102419. doi: 10.1183/13993003.02419-2021.
