Acceleron Pharma presented positive topline results from the phase 2 PULSAR trial evaluating sotatercept versus placebo for the treatment of patients with Pulmonary Arterial Hypertension. The data presented during the ‘Breaking News’ Session of the American Thoracic Society 2020 Virtual Conference (ATS 2020 Virtual) show the PULSAR trial achieved its primary endpoint by demonstrating a statistically significant mean reduction in pulmonary vascular resistance.
The double-blind, placebo-controlled study enrolled 106 patients who were randomized to receive placebo, 0.3 mg/kg of sotatercept, or 0.7 mg/kg of sotatercept subcutaneously every 21 days in combination with stable background PAH-specific therapies, including mono, double, and triple therapy over a 24-week treatment period. Of the 106 patients participating in the trial, 35% were receiving double background PAH-specific therapies and 56% were receiving triple background PAH-specific therapies. The patients who were treated with 0.3 mg/kg or 0.7 mg/kg of sotatercept experienced mean PVR reductions of approximately 21% and 34%, respectively, versus 2.1% for placebo. The trial also achieved a statistically significant all-dose mean improvement from baseline of 54 meters in the key secondary endpoint of six-minute walk distance (6MWD) and a placebo corrected improvement of 25 meters (all doses combined). Sotatercept was generally well tolerated; adverse events were consistent with previously published data on sotatercept in clinical trials in other patient population.
Sotatercept is an investigational agent designed to be a selective ligand trap for members of the TGF-beta superfamily to rebalance BMPR-II signaling, which is a key molecular driver of PAH. In preclinical research recently published in Science Translational Medicine, sotatercept exhibited consistent effects across multiple components of disease, including suppressed proliferation of pulmonary arterial smooth muscle and microvascular endothelial cells, reduced pulmonary pressures, lessened right ventricular hypertrophy, improved right ventricular function, and attenuated vascular remodeling. Sotatercept is part of a licensing agreement with Bristol Myers Squibb
Sotatercept has been granted Breakthrough Therapy designation from the U.S. Food and Drug Administration and Priority Medicine (PRIME) designation from the European Medicines Agency in PAH.
PAH is a rare and chronic, rapidly progressing disorder characterized by the constriction of small pulmonary arteries and elevated blood pressure in the pulmonary circulation. PAH results in significant strain on the heart, often leading to limited physical activity, heart failure, and reduced life expectancy. The 5-year survival rate for patients with PAH is approximately 57%. Available therapies generally act by promoting the dilation of pulmonary vessels without addressing the underlying cause of the disease. As a result, PAH often progresses rapidly for many patients despite standard of care treatment. A growing body of research has implicated imbalances in BMP and TGF-beta signaling as a primary driver of PAH in familial, idiopathic, and acquired forms of the disease.