PULSAR: A phase 2, randomized, double-blind, placebo-controlled study to assess the efficacy and safety of sotatercept (ACE-011) when added to standard of care (SOC) for treatment of pulmonary arterial hypertension (PAH)

Background: Novel therapies are needed to attenuate the progression of PAH. Disruptions in transforming growth-factor (TGF)-β and bone morphogenetic protein (BMP) signaling are associated with the development of PAH. Sotatercept (ACE-011) is a first-in-class fusion protein consisting of the extracellular domain of activin receptor IIa (ActRIIa) attached to the Fc portion of human IgG1 that sequesters TGF-β superfamily ligands such as activin A and B and growth differentiation factor (GDF)-11 to suppress TGF-β signaling and rebalance deficient BMPR2 signaling. Aims: To determine the efficacy and safety of sotatercept versus placebo when administered with SOC in adults with PAH. Methods: Eligible participants (pts) have World Health Organization (WHO) Group 1 functional class II-III PAH; age ≥18 years; baseline pulmonary vascular resistance (PVR) of ≥5 Wood units; 6-minute walk distance (6MWD) of 150–550m; and stable PAH SOC therapy. One hundred pts will be randomized 3:3:4 to placebo, 0.3 mg/kg sotatercept, or 0.7 mg/kg sotatercept administered SC every 21 days plus SOC for 24 weeks. The primary endpoint is change from baseline in PVR at 24 weeks. An 18-month extension period follows. Results and Conclusions: Primary analysis results for PULSAR (NCT03496207) are expected in the first half of 2020. A related study (SPECTRA; NCT03738150) will evaluate the effects of sotatercept on cardiopulmonary hemodynamics and functional capacity in pts with PAH.