Preclinical Data Supports Sotatercept Being Tested in People with PAH, Acceleron Reports

Preclinical work supports the potential of  sotatercept to be a first-in-class disease-modifying therapy for pulmonary arterial hypertension (PAH) and to moving the investigational therapy into a Phase 2 trial in patients, Acceleron Pharma announced.

Sotatercept is a  trap molecule for members of the transforming growth factor-beta (TGF-beta) superfamily. A growing body of evidence has implicated imbalances in TGF-beta signaling as a primary driver of PAH development.

The new findings were part of a presentation titled ”ACTRIIA-Fc rebalances BMP and activin/TGF-β signaling to attenuate experimental pulmonary hypertension” delivered at the American Heart Association (AHA) 2017 Scientific Sessions in Anaheim, California, in mid-November.

Data show the therapy has positive effects on several aspects of vascular remodeling and heart disease.

“We are extremely encouraged by these positive preclinical results, which support our mechanistic approach for sotatercept and its potential to be a first-in-class disease-modifying therapy for patients with pulmonary arterial hypertension,” Ravi Kumar, chief scientific officer for Acceleron, said in a press release.

“We look forward to initiating a Phase 2 trial with sotatercept in PAH during the first half of 2018,”  Kumar added.

The data, presented by Paul Yu, an associate professor of medicine at Brigham and Women’s Hospital, is from three animal models of PAH given sotatercept at different stages of the disease.

In those with early disease, treatment blocked progression of pulmonary vascular remodeling and right heart failure. It also prevented an increase in pulmonary arterial pressure.

Sotatercept given to animals with established disease was seen to decrease the thickness of pulmonary blood vessels (arterioles) compared to untreated animals. Treated animals also showed lower muscularization of pulmonary blood vessels — the second major detrimental effect of PAH — and better pulmonary arterial pressures, culminating in a lower risk for right heart failure.

“The … preclinical results show remarkable biological activity, particularly on the pulmonary vasculature, across multiple, well-established animal models of PAH,”  Yu said. “These results … further establish the importance of signaling by the TGF-beta superfamily as a target for therapies to treat PAH.”

Acceleron obtained the rights from Celgene to develop and commercialize sotatercept as a treatment for PAH in September 2017, under a collaboration agreement signed in 2008.