Acceleron Pharmaceuticals announced that the PULSAR Phase 2 trial of sotatercept for pulmonary arterial hypertension (PAH) met its primary endpoint- a statistically significant reduction in pulmonary vascular resistance, in addition to key secondary endpoints.
The PULSAR trial is a randomized, double-blind, placebo-controlled study designed to evaluate the efficacy and safety of sotatercept in PAH patients. A total of 106 patients were randomized in a 3:3:4 ratio to receive placebo, sotatercept 0.3 mg/kg, or sotatercept 0.7 mg/kg subcutaneously every 21 days with standard-of-care therapies in combination. The primary endpoint of the trial is the change from baseline in pulmonary vascular resistance (PVR) over a 24-week treatment period. PVR, as measured by right heart catheterization, is the resistance that the heart must overcome to pump blood through the pulmonary circulatory system. The key secondary endpoint was six-minute walk distance (6MWD; a measure of functional capacity/endurance). The trial was powered to detect an 18% reduction in the primary endpoint of PVR and a 24-meter improvement in the secondary endpoint of 6MWD.
In patients on stable background PAH-specific therapies, sotatercept demonstrated a statistically significant reduction in PVR at week 24 versus placebo. The trial also achieved a statistically significant improvement in the key secondary endpoint of 6MWD, as well as other secondary endpoints, including NT-proBNP, and WHO functional class.
Sotatercept was generally well tolerated in the trial. Adverse events observed in the study were generally consistent with previously published data on sotatercept in other diseases.
Acceleron plans to present a detailed review of the topline results from the PULSAR trial of sotatercept at a medical conference later this year.
Sotatercept is 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 studies of PAH, sotatercept reversed pulmonary vessel muscularization and improved indicators of right heart failure.
About Pulmonary Arterial Hypertension
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.