Acceleron announces positive phase 2 trial results for PAH drug

Sotatercept met the primary and key secondary endpoints of the PULSAR phase 2 trial in patients with pulmonary artery hypertension, according to the press release from Acceleron Pharma.

In this phase 2 trial, 106 patients were randomly assigned placebo or sotatercept (Acceleron Pharma) 0.3 mg/kg or 0.7 mg/kg every 21 days in combination with stable background PAH-specific therapies for 24 weeks. Sotatercept showed a statistically significant reduction in pulmonary vascular resistance — the primary endpoint — and improvement in 6-minute walk distance — a key secondary endpoint — in patients with PAH. The drug was also well tolerated.

“Approved therapies for patients with PAH target three main pathways of endothelial cell dysfunction to primarily promote pulmonary vasodilation,” Marc Humbert, MD, PhD, an investigator for the PULSAR trial and professor of medicine and director of the French Pulmonary Hypertension Reference Center at the Université Paris-Saclay, said in the release. “As a selective ligand trap for members of the [transforming growth factor]-beta superfamily, sotatercept is designed to rebalance [bone morphogenic protein type II receptor] 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,” Vallerie McLaughlin, MD, also a PULSAR trial investigator and professor of medicine and director of the pulmonary hypertension program at the University of Michigan, said in the release. “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.”

Of the 106 patients enrolled in the PULSAR trial, 97 are currently participating in the 18-month extension. No patients have discontinued participation in the PULSAR trial.

“We look forward to upcoming interactions with health authorities as we plan to globally develop and, if approved, commercialize sotatercept in PAH,” Habib Dable, president and CEO of Acceleron, said in the release.

Acceleron plans to present a review of the top-line results from the trial at a medical conference later this year. Sotatercept is not yet approved for use in any country.

Disclosures: Humbert and McLaughlin report they are paid consultants to Acceleron.