Sotatercept for the treatment of pulmonary arterial hypertension: PULSAR open-label extension
The European respiratory journal
BACKGROUND: In participants with pulmonary arterial hypertension, 24 weeks of sotatercept resulted in a significantly greater reduction from baseline in pulmonary vascular resistance than placebo. This report characterises the longer-term safety and efficacy of sotatercept in the PULSAR open-label extension. We report cumulative safety, and efficacy at months 18-24, for all participants treated with sotatercept. METHODS: PULSAR was a phase 2, randomised, double-blind, placebo-controlled study followed by an open-label extension, which evaluated sotatercept on top of background pulmonary arterial hypertension therapy in adults. Participants originally randomised to placebo were re-randomised 1:1 to sotatercept 0.3 or 0.7 mg·kg (placebo-crossed group); those initially randomised to sotatercept continued the same sotatercept dose (continued-sotatercept group). Safety was evaluated in all participants who received ≥1 dose of sotatercept. The primary efficacy endpoint was change from baseline to months 18-24 in pulmonary vascular resistance. Secondary endpoints included 6-min walk distance and functional class. Two prespecified analyses, placebo-crossed and delayed-start, evaluated efficacy irrespective of dose. RESULTS: Of 106 participants enrolled in the PULSAR study, 97 continued into the extension period. Serious treatment-emergent adverse events were reported in 32 (30.8%) participants; 10 (9.6%) reported treatment-emergent adverse events leading to study discontinuation. Three (2.9%) participants died, none considered related to study drug. The placebo-crossed group demonstrated significant improvement across primary and secondary endpoints and clinical efficacy was maintained in the continued-sotatercept group. CONCLUSION: These results support the longer-term safety and durability of clinical benefit of sotatercept for pulmonary arterial hypertension.
Humbert, Marc; McLaughlin, Vallerie; Gibbs, J Simon; Gomberg-Maitland, Mardi; Hoeper, Marius M.; Preston, Ioana R.; Souza, Rogerio; Waxman, Aaron B.; Ghofrani, Hossein-Ardeschir; Escribano Subias, Pilar; Feldman, Jeremy; Meyer, Gisela; Montani, David; Olsson, Karen M.; Manimaran, Solaiappan; de Oliveira Pena, Janethe; and Badesch, David B., "Sotatercept for the treatment of pulmonary arterial hypertension: PULSAR open-label extension" (2022). GW Authored Works. Paper 1421.