FDA Approves First Activin Signaling Inhibitor Therapy in Patients with PAH

Jessica Bard

The FDA has granted approval for a novel therapy for the management of patients with pulmonary arterial hypertension (PAH). The newly approved therapy, sotatercept-csrk, represents a significant advancement in the management of patients with PAH, as this approval marks the first for an activin signaling inhibitor therapy in patients with PAH.

PAH is a rare and life-threatening disease and “it leads to vascular remodeling in the lung,” STELLAR trial investigator, Zeenat Safdar, MD, MS, said in an interview with Consultant360.

“And this vascular remodeling leads to the thickening of the vessels in the lungs and leads to increased pulmonary vascular resistance. Because of that, it leads to right heart failure. So, as you can imagine, it's a progressive disease. It happens in females; [it is] predominantly a female disease.”

The approval of sotatercept-csrk is based on results from the Phase 3 STELLAR trial, which demonstrated notable clinical benefits compared with standard therapy alone.1 Patients treated with sotatercept-csrk experienced a significant increase in exercise capacity, improvement in WHO functional class, and a reduction in the risk of clinical worsening events.

“Most of these patients that were on the clinical trial, they were on background therapy of two drugs or three drugs,” Dr Safdar said. “And despite being on maximum background therapy, these patients, still in heart failure, were not doing well. There was still an area which they needed improvement in their disease state. And in the studies, it has been clearly shown that sotatercept treatment had actually helped these patients a lot.”

Health care providers administering sotatercept-csrk should closely monitor patients for potential adverse effects, including changes in hemoglobin and platelet levels, which may necessitate dose adjustments. Despite potential risks, the approval of sotatercept-csrk offers hope for patients with PAH, providing a new avenue for managing this debilitating condition.

Sotatercept-csrk is administered via subcutaneous injection every 3 weeks and is expected to be available in the United States by the end of April.

“We are very happy and very excited for the patients because now we have another drug, which is targeting a brand-new pathway that's FDA-approved, and that can help patients who are already on maximum therapy," Dr Safdar said. "Previously, if a patient was on maximum therapy and we couldn't put them on any other medication, the only option left was for a lung transplant. And as some of you know, lung transplantation is not an easy thing to do.”


  1. Hoeper MM, Badesch DB, Ghofrani HA, et al; STELLAR Trial Investigators. Phase 3 trial of sotatercept for treatment of pulmonary arterial hypertension. N Engl J Med. 2023;388(16):1478-1490. doi:10.1056/NEJMoa2213558

Watch Dr Safdar’s full interview on