Acceleron Pharma Science & Pipeline

Science & Pipeline

Sotatercept is an investigational product being studied in patients with pulmonary arterial hypertension (PAH) – a rare, progressive, and life-threatening blood vessel disorder.

Sotatercept is a ligand trap with high selectivity for multiple proteins within the TGF-beta superfamily, including activins, GDFs, and others. With its believed ability to block the TGF-beta superfamily signaling pathway, sotatercept could promote a rebalancing of bone morphogenetic protein receptor type II (BMPR-II) signaling and, potentially, restore vascular homeostasis. In preclinical research published in Science Translational Medicine, sotatercept exhibited consistent effects across multiple components of disease, including suppressed proliferation of pulmonary arterial smooth muscle and microvascular endothelial cells, reduced pulmonary pressures, lessened right ventricular hypertrophy, improved right ventricular function, and attenuated vascular remodeling.

PAH is characterized by a thickening of the pulmonary vasculature, leading to restricted blood flow and elevated blood pressure within the pulmonary vessels. To compensate, the heart must work harder to push blood through the pulmonary arteries.

Currently approved PAH treatments target several main pathways that primarily promote dilation of the pulmonary vessels to reduce pulmonary vascular resistance. These therapies have been used alone or in combination to improve exercise capacity and slow the progression of the disease. However, no existing therapy directly addresses the underlying cellular proliferation that leads to increased pulmonary arterial pressure. In PAH, signaling via BMPR-II is imbalanced, allowing greater influence from the adjacent activin receptor pathway, further promoting cellular proliferation and vascular remodeling.

Acceleron presented results from the sotatercept Phase 2 PULSAR trial in patients with PAH during the “Breaking News: Clinical Trial Results in Pulmonary Medicine” session of the American Thoracic Society 2020 Virtual Conference in June 2020. The United States Food and Drug Administration (FDA) has granted Orphan Drug designation and Breakthrough Therapy designation to sotatercept for the treatment of PAH; the European Medicines Agency (EMA) has granted Priority Medicines (PRIME) designation to sotatercept for the treatment of PAH.

Additional clinical studies of sotatercept include the SPECTRA Phase 2 trial, which is designed to continue to assess the efficacy and safety of sotatercept in patients with PAH, and we are currently planning multiple Phase 3 trials with the potential to support a long-term vision of establishing sotatercept as a backbone therapy for patients with PAH in all stages of the disease. We recently initiated our main registrational Phase 3 trial, known as STELLAR.

Sotatercept, which is part of a licensing agreement with Bristol Myers Squibb, is an investigational therapy that is not approved for any use in any country.





Phase 1Ph1Phase 2Ph2Phase 3Ph3ApprovedApp
Pulmonary Arterial Hypertension
Pulmonary Arterial Hypertension
ZENITH Trial (planned)ZENITH Trial (planned)ZENITH