Sotatercept for the Treatment of Pulmonary Arterial Hypertension

Marc Humbert (1) , Vallerie Mclaughlin , J. Simon R. Gibbs , Mardi Gomberg-Maitland , Marius Hoeper , Ioana Preston , Rogerio Souza , Aaron Waxman , Pilar Escribano Subias , Jeremy Feldman , Gisela Meyer , David Montani (1) , Karen Olsson , Solaiappan Manimaran , Jennifer Barnes , Peter Linde , Janethe de Oliveira Pena , David Badesch , Arnaud Bourdin (2, 3)

1 HPPIT - Hypertension arterielle pulmonaire physiopathologie et innovation thérapeutique
2 PhyMedExp - Physiologie & médecine expérimentale du Cœur et des Muscles [U 1046]
3 CHRU Montpellier - Centre Hospitalier Régional Universitaire [Montpellier]

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−5 (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−5 (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. opens in new tab.)

Domaines: Cardiologie et système cardiovasculaire; Pneumologie et système respiratoire; Pharmacologie

Marc Humbert, Vallerie Mclaughlin, J. Simon R. Gibbs, Mardi Gomberg-Maitland, Marius Hoeper, et al.. Sotatercept for the Treatment of Pulmonary Arterial Hypertension. New England Journal of Medicine, 2021, 384 (13), pp.1204-1215. ⟨10.1056/NEJMoa2024277⟩. ⟨hal-03270003⟩