Acceleron's PAH Treatment Hits Primary Endpoint in Mid-Stage Trial

Shares of Acceleron Pharma have spiked more than 57% in premarket trading after the company revealed late Monday that its Phase II 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, Cambridge, Mass.-based Acceleron said 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 six-minute-walk-distance (6MWD), as well as other secondary endpoints, including NT-proBNP, and WHO functional class.

Habib Dable, president and chief executive officer of Acceleron, said he was “thrilled” about the positive results from the mid-stage PULSAR trial. 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. Dable said PAH is a debilitating disease with a high unmet need and the Phase II data is encouraging. It signals 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,” Dable said in a statement.

If approved, sotatercept would compete with PAH drugs already on the market, such as United Therapeutics top-selling PAH drug, Remodulin. Other approved drugs include Actelion’s Tracleer and Pfizer’s Revatio.

Acceleron did not provide a detailed analysis of the trial results. The company plans to present a detailed review of the topline results from the PULSAR Phase II trial of sotatercept at a medical conference later this year.

Sotatercept is an investigational agent designed to be a selective ligand trap for members of the TGF-beta superfamily to rebalance BMPR2 signaling, which is a key molecular driver of PAH, a rare progressive disorder that is characterized by the constriction of pulmonary arteries and elevated blood pressure in the pulmonary circulation. Last year, sotatercept received Orphan Drug Designation from the U.S. Food and Drug Administration as a potential treatment for PAH, a progressive disease that results in heart failure and shortened life expectancy of nearly 52,000 patients in the United States.

Over the 24-week period of treatment, Acceleron said 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.

Marc Humbert, director of the French Pulmonary Hypertension Reference Center at the Université Paris-Saclay and an investigator in the Acceleron trial, said 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, Humbert said in a statement.

Acceleron’s Phase II data follows the company’s December deal with Fulcrum Therapeutics to tackle pulmonary diseases.