FDA and EMA designations for Acceleron’s Sotatercept highlight potential to differentiate in PAH space

Acceleron Pharma’s sotatercept, was granted priority designation by the European Medicines Agency for pulmonary arterial hypertension (PAH) in May 2020. This further signifies the drug’s major advantages over existing treatments, and will provide enhanced support for its development for targeting underlying disease progression in PAH, according to GlobalData, a leading data and analytics company.

The EMA priority designation followed sotatercept’s 2020 FDA breakthrough therapy designation and 2019 FDA orphan drug designation for the same indication. A Phase II PULSAR trial, which included severely sick PAH patients, demonstrated a statistically significant reduction in pulmonary vascular resistance (PVR) in comparison to placebo.

Existing PAH treatments target multiple pathways to dilate pulmonary vessels to lower PVR. These PAH therapies are used as monotherapy and in combinations to improve exercise capacity and delay progression of the disease. However, no existing treatments directly address underlying disease progression.

Kajal Jaddoo, Associate Pharma Analyst at GlobalData, comments: “If the clinical development of sotatercept is successful, it’ll likely become an add-on agent and not displace any current therapies. As a result, patients on endothelin receptor antagonists (ERAs), PDE5s and prostacyclins would be receiving sotatercept as a fourth agent. However, due to this quadruple therapy, patients may be at risk of developing even more side effects. In addition, Acceleron Pharma is not established in the PAH market and will likely face marketing challenges from already-established PAH drug giants United Therapeutics and Johnson & Johnson.”

Sotatercept is a dimeric fusion protein containing the extracellular domain of the activin receptor 2A fused to the Fc domain of human IgG1. It increases hemoglobin levels and red blood cells in humans by blocking the transforming growth factor beta (TGF-beta) superfamily pathway. It’s administered intravenously and subcutaneously.

Jaddoo concludes: “Sotatercept prevents blood vessel remodeling by restoring vascular homeostasis between cell proliferation and apoptosis by signaling via the bone morphogenetic protein receptor type 2, positioning it as a potential major advancement in the treatment on PAH. Key opinion leaders interviewed by GlobalData have emphasized that the PULSAR trial proved to be successful in reducing PVR and opined that sotatercept has the potential to become the most promising development in PAH over the next five to ten years.”

More Media