Acceleron Pharma, a biopharmaceutical company focused on rare diseases, has announced the start of the PULSAR Phase 2 clinical trial assessing the safety and effectiveness of sotatercept (ACE-011) in adults with pulmonary arterial hypertension (PAH).
Sotatercept works by trapping members of the transforming growth factor-beta (TGF-beta) family, particularly those directly involved in the BMP pathway, a cellular mechanism that plays a key role in the maintenance of a healthy pulmonary vasculature.
Studies have demonstrated an association between PAH onset and imbalances in TGF-beta signaling.
Preclinical studies in PAH animal models showed that sotatercept significantly improved pulmonary arterial pressure, decreased pulmonary vessel muscularization, and decreased indicators of heart failure.
“The initiation of the PULSAR trial is an important milestone in our newly expanded research and development efforts in pulmonary disease,” said Habib Dable, CEO of Acceleron. “We believe that treatment with sotatercept could restore a vital signaling pathway that is known to be deficient in PAH patients. This is an extremely important trial, as we hope to bring an innovative medicine to the thousands of patients who are suffering from PAH.”
In the randomized, double-blind, placebo-controlled PULSAR trial (NCT03496207), 90 PAH patients will receive either sotatercept or placebo, in addition to standard vasodilator therapies. Participants will be randomly divided into three groups, receiving either an under-the-skin administration of 0.3 mg/kg of sotatercept, 0.7 mg/kg of sotatercept, or placebo every 21 days for six months.
The study is currently recruiting at a single site in Phoenix, Arizona. Following the initial six-month treatment, participants will be eligible to enroll in an 18-month extension period.
The primary objective of the study is the change in pulmonary vascular resistance from the start of the study over the treatment period.
Secondary goals include changes in the distance walked based on the six-minute walk test, which measures exercise capacity. Quality of life questionnaires and echocardiography tests will also be conducted.
“There is a real need for new treatment options that have the potential to improve survival for PAH patients,” David Badesch, MD, director of the Pulmonary Hypertension Program at the University of Colorado and chair of the PULSAR Trial Steering Committee, said in a press release.
“Based on its novel mechanisms and preclinical results, sotatercept, particularly in combination with standard-of-care therapies, could be an important advancement in the future treatment of PAH. I look forward to the results of the trial,” he said.
Preliminary trial results are expected to be reported in the first half of 2020.