Science & Pipeline
Acceleron has expanded its TGF-beta protein superfamily research and development expertise to include pulmonary disease, with a first potential indication in pulmonary arterial hypertension (PAH)—a rare, progressive, and life-threatening blood vessel disorder.
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. As the disease progresses, the right ventricle of the heart eventually fails.
Currently approved PAH treatments target three main pathways that 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 causes PAH’s hallmark vascular remodeling. In PAH, signaling via the bone morphogenetic protein receptor type II (BMPR2) is imbalanced, allowing greater influence from the adjacent activin receptor pathway, further promoting cellular proliferation and vascular remodeling.
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 BMPR2 signaling and, potentially, restore vascular homeostasis. In preclinical models of PAH, sotatercept has demonstrated the potential to reverse pulmonary vascular muscularization, cellular proliferation, and right ventricular hypertrophy and to reduce pulmonary arterial pressures.
Based on its preclinical profile and apparent ability to rebalance BMPR2 signaling, we believe that sotatercept could be potentially disease-modifying and transform the PAH treatment landscape.
Acceleron is now conducting the PULSAR and SPECTRA Phase 2 clinical trials to assess the efficacy and safety of sotatercept in patients with PAH and expects to report top-line results from the PULSAR trial during the first quarter of 2020. In September 2019, the United States Food and Drug Administration (FDA) granted Orphan Drug designation to sotatercept for the treatment of PAH.
Sotatercept is an investigational therapy that is not approved for any use in any country.
|PreclinicalPre||Phase 1Ph1||Phase 2Ph2||Phase 3Ph3||ApprovedApp|
|Pulmonary Arterial Hypertension|
Pulmonary Arterial Hypertension
PULSAR TrialPULSAR Trial
SPECTRA Exploratory TrialSPECTRA Trial
The vascular thickening or remodeling that occurs in PAH restricts blood flow to the lungs. As a result, circulating blood oxygen levels drop, causing patients to experience shortness of breath, chest pain, dizziness, fainting, swelling in arms and legs (edema), and palpitations.
Because of the disease’s progressive nature, one in three patients dies within five years of diagnosis, despite treatment with approved PAH therapies. Patients may benefit from a combination of lifestyle changes, medicines, and surgeries; however, everyday activities, such as walking and showering, become more difficult, leaving many patients dependent on supplementary oxygen.