Sotatercept for the Treatment of Pulmonary Arterial Hypertension.

Marc Humbert Vallerie McLaughlin J Simon R Gibbs Mardi Gomberg-Maitland Marius M Hoeper Ioana R Preston Rogerio Souza Aaron Waxman Pilar Escribano Subias Jeremy Feldman Gisela Meyer David Montani Karen M Olsson Solaiappan Manimaran Jennifer Barnes Peter G Linde Janethe de Oliveira Pena David B Badesch

N Engl J Med

From the 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 (M.H., D.M.); the Division of Cardiovascular Medicine, Department of Internal Medicine, University of Michigan Health System, Ann Arbor (V.M.); the National Heart and Lung Institute, Imperial College London, and the National Pulmonary Hypertension Service, Hammersmith Hospital, Imperial College Healthcare NHS Trust, London (J.S.R.G.); the Department of Medicine, George Washington University, Washington, DC (M.G.-M.); the Department of Respiratory Medicine, Hannover Medical School, and the German Center for Lung Research - both in Hannover, Germany (M.M.H., K.M.O.); the Division of Pulmonary, Critical Care and Sleep Medicine, Tufts Medical Center (I.R.P.), and the Division of Pulmonary and Critical Care Medicine, Department of Medicine, Brigham and Women's Hospital (A.W.), Boston, and Acceleron Pharma, Cambridge (S.M., J.B., P.G.L., J.O.P.) - all in Massachusetts; the Pulmonary Division-Heart Institute, University of São Paulo Medical School, São Paulo (R.S.), and Complexo Hospitalar Santa Casa de Porto Alegre, Pulmonary Vascular Research Institute, Porto Alegre (G.M.) - both in Brazil; the Department of Cardiology, Centro de Investigación en Red en Enfermedades Cardiovasculares, Hospital Universitario 12 de Octubre, Universidad Complutense, Madrid (P.E.S.); Arizona Pulmonary Specialists, Phoenix (J.F.); and the Divisions of Pulmonary Sciences and Critical Care Medicine, and Cardiology, University of Colorado, Anschutz Medical Campus, Aurora (D.B.B.).

Published: April 2021

Pulmonary arterial hypertension (PAH) involves changes in lung blood vessels and poor outcomes, and the novel drug sotatercept aims to fix dysfunctional signaling in this process.* -
In a 24-week study with 106 participants, those receiving sotatercept showed significant improvements in pulmonary vascular resistance compared to the placebo group, particularly at dosages of 0.3 mg and 0.7 mg.* -
While sotatercept improved exercise capacity and reduced certain biomarkers, common side effects included lowered platelet count and increased hemoglobin, with one serious adverse event reported.*

Background: Pulmonary arterial hypertension is characterized by pulmonary vascular remodeling, cellular proliferation, and poor long-term outcomes. Dysfunctional bone morphogenetic protein pathway signaling is associated with both hereditary and idiopathic subtypes. Sotatercept, a novel fusion protein, binds activins and growth differentiation factors in the attempt to restore balance between growth-promoting and growth-inhibiting signaling pathways.

Methods: In this 24-week multicenter trial, we randomly assigned 106 adults who were receiving background therapy for pulmonary arterial hypertension to receive subcutaneous sotatercept at a dose of 0.3 mg per kilogram of body weight every 3 weeks or 0.7 mg per kilogram every 3 weeks or placebo. The primary end point was the change from baseline to week 24 in pulmonary vascular resistance.

Results: Baseline characteristics were similar among the three groups. The least-squares mean difference between the sotatercept 0.3-mg group and the placebo group in the change from baseline to week 24 in pulmonary vascular resistance was -145.8 dyn · sec · cm (95% confidence interval [CI], -241.0 to -50.6; P = 0.003). The least-squares mean difference between the sotatercept 0.7-mg group and the placebo group was -239.5 dyn · sec · cm (95% CI, -329.3 to -149.7; P<0.001). At 24 weeks, the least-squares mean difference between the sotatercept 0.3-mg group and the placebo group in the change from baseline in 6-minute walk distance was 29.4 m (95% CI, 3.8 to 55.0). The least-squares mean difference between the sotatercept 0.7-mg group and the placebo group was 21.4 m (95% CI, -2.8 to 45.7). Sotatercept was also associated with a decrease in N-terminal pro-B-type natriuretic peptide levels. Thrombocytopenia and an increased hemoglobin level were the most common hematologic adverse events. One patient in the sotatercept 0.7-mg group died from cardiac arrest.

Conclusions: Treatment with sotatercept resulted in a reduction in pulmonary vascular resistance in patients receiving background therapy for pulmonary arterial hypertension. (Funded by Acceleron Pharma; PULSAR ClinicalTrials.gov number, NCT03496207.).

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http://dx.doi.org/10.1056/NEJMoa2024277	DOI Listing

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