Sotatercept reduces pulmonary vascular resistance in PAH, finds clinical trial

The data presented virtually at the American Thoracic Society (ATS) 2020 Virtual Sessions this week by investigators showed that Sotatercept resulted in a statistically significant reduction in pulmonary vascular resistance when compared to placebo, the primary endpoint of the 24 week trial.

Sotatercept is an investigational agent that reversed pulmonary vessel muscularization and improved indicators of right heart failure in clinical trials.In April, the FDA granted breakthrough therapy designation to sotatercept for treatment of Pulmonary Arterial Hypertension.

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, 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 trial achieved its primary endpoint, key secondary endpoint, and showed concordance of results across multiple additional endpoints and regardless of baseline characteristics.

The trial also achieved the protocol-defined improvement in the key secondary endpoint of 6MWD at 24 weeks. Both sotatercept dose groups achieved at least a 50-meter (LS mean) increase from baseline, as demonstrated in the 0.3 mg/kg group (58 meters) and the 0.7 mg/kg group (50 meters), allowing for a pre-specified pooled analysis. Overall, treatment with sotatercept (pooled analysis) achieved a 54-meter (LS mean) change from baseline and a placebo-corrected (LS mean) difference of 25 meters (nominal p=0.03).

The study drug was generally well-tolerated, and in at least 10% of all patients adverse effects included headache, diarrhea, peripheral edema, dizziness, fatigue, hypokalemia, and nausea.

We're thrilled to report the impressive magnitude of the positive effects that sotatercept, in combination with current therapies, was able to achieve in patients with PAH," said Habib Dable, President and Chief Executive Officer of Acceleron. "Although the introduction over the past two decades of more than a dozen treatments for PAH has driven the development of today's combination-therapy strategies, the substantial morbidity still associated with PAH clearly signals the need for a new approach. As we work now with health authorities to move sotatercept into Phase 3 testing, we are increasingly encouraged that we will be able to deliver a truly innovative therapy to patients with this debilitating disease."