PULSAR Phase 2 Trial Met Primary Endpoints in Patients with Pulmonary Arterial Hypertension
Acceleron Pharma Inc, a leading biopharmaceutical company in the discovery and development of TGF-beta superfamily therapeutics to treat serious and rare diseases, announced that the PULSAR Phase 2 trial of sotatercept met its primary and key secondary endpoints in patients with pulmonary arterial hypertension (PAH).
In patients on stable background PAH-specific therapies, sotatercept demonstrated a statistically significant reduction in pulmonary vascular resistance (PVR), the trial’s primary endpoint, 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.
“We’re thrilled to report such positive topline results from the PULSAR trial,” said Habib Dable, President and Chief Executive Officer of Acceleron in a press release. “PAH is a debilitating disease of high unmet medical need, so we’re encouraged by these data that signal that sotatercept could deliver added benefit to patients. We look forward to upcoming interactions with health authorities as we plan to globally develop and, if approved, commercialize sotatercept in PAH.”
In this Phase 2 double-blind, placebo-controlled study, 106 patients 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 over a 24-week treatment period.
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.
“Approved therapies for patients with PAH target three main pathways of endothelial cell dysfunction to primarily promote pulmonary vasodilation,” said Dr. Marc Humbert*, Professor of Medicine and Director of the French Pulmonary Hypertension Reference Center at the Université Paris-Saclay. “As a selective ligand trap for members of the TGF-beta superfamily, sotatercept is designed to rebalance BMPR-II signaling, which is a key molecular driver of PAH. The PULSAR data demonstrate that this novel approach has the potential to provide significant benefit on top of currently available therapies.”
“These results are particularly impressive given the patient population, the majority of whom were on background combination therapy, including parenteral prostacyclins, had advanced hemodynamics and lengthy duration of disease,” said Dr. Vallerie McLaughlin [*] , Professor of Medicine and Director of the Pulmonary Hypertension Program at the University of Michigan. “Exceptionally notable was the concordance of the effects across the prespecified subgroups. These clinically meaningful data raise the exciting possibility that sotatercept could potentially shift the treatment paradigm for patients with PAH.”
97 out of the 106 patients who enrolled in the PULSAR trial are currently participating in the 18-month extension period of the trial. To date, no patients have discontinued participation in the extension trial.
Acceleron plans to present a detailed review of the topline results from the PULSAR Phase 2 trial of sotatercept at a medical conference later this year.
Sotatercept is an investigational therapy that is not approved for any use in any country.
*Drs. McLaughlin and Humbert are investigators in the PULSAR trial and are paid consultants to Acceleron.