Long-Term Sotatercept Data Support Durability for PAH, with Ioana Preston, MD

After decades of limited innovation in pulmonary arterial hypertension (PAH) treatment, sotatercept (Winrevair) is emerging as a potential game changer.1

New pooled data from multiple trials—including participants who have completed the PULSAR, SPECTRA, or STELLAR studies and have continued in the ongoing open-label extension study, SOTERIA—highlight the biologic’s efficacy and sustained safety when added to background therapy for the treatment of PAH. Of note, these results represent the largest analysis of sotatercept to date.1

A rare, progressive condition characterized by narrowing blood vessels within the lungs, approximately 500-1000 new cases of PAH are diagnosed each year in the US, according to the American Lung Association. Given the progressive nature of the disease, improving standard of care stands to have a significant impact on quality of life for affected patients.2

“Before sotatercept was developed, we have had treatments for pulmonary arterial hypertension affecting 3 important pathways: the endothelial pathway, the prostacyclin pathway, and the nitric oxide pathway,” Ioana Preston, MD, an associate professor of medicine and director of the Pulmonary Hypertension Center at Tufts Medical Center, explained to HCPLive. “Despite having these therapies that are effective, the disease burden has remained serious, and there has been continuous unmet need for developing new therapies.”

A first-in-class activin-signaling inhibitor, sotatercept offers a novel therapeutic alternative to vasodilators in the treatment of PAH by binding proproliferative members of the transforming growth factor β superfamily, targeting pulmonary vascular remodeling.3 On March 26, 2024, the US Food and Drug Administration granted approval to sotatercept for the treatment of adults with PAH based on data from the phase 3 STELLAR trial.2

At the American Thoracic Society’s (ATS) 2025 International Conference, Preston presented pooled data from participants who completed the PULSAR, SPECTRA, or STELLAR studies and have continued in the ongoing open-label extension study, SOTERIA, evaluating the long-term safety, tolerability and efficacy of sotatercept when added to background therapy for the treatment of PAH.1

“This is the second interim, long-term analysis that showed that sotatercept overall maintains the safety profile that we learned from the parent studies,” Preston explained, highlighting bleeding events as the most common adverse events and noting that most were non-serious. “The other important aspect of the long term safety data was that longer exposure to sotatercept in patients with PAH does not reflect an increased risk of side effects, but a stable safety profile and the stable occurrence of side effects. On the other hand, if we look at the follow up efficacy data by the 6 minute walk distance, functional class, and NT-proBNP, the improvement that was achieved at 24 weeks in these 3 parameters was maintained at 2 years of follow up.”

Looking ahead, Preston says the field needs to continue its work in achieving improvement, stabilization, and cure of patients with PAH. With respect to sotatercept and its role in the paradigm of PAH treatment, she says future research must explore whether it should be initiated earlier in the disease process and whether it can be used upfront in combination with other therapies.

Editors’ note: Preston has relevant disclosures with United Therapeutics, Liquidia, Merck, Janssen, Respira, and Gossamer.

References

1. Merck. Preliminary results from a pooled analysis of clinical trial data evaluating the long-term safety and favorable benefit-risk profile of WINREVAIR™ to be featured as a late-breaking presentation. May 16, 2025. Accessed June 12, 2025. https://www.merck.com/news/merck-to-present-new-clinical-and-outcomes-research-data-at-the-american-thoracic-societys-ats-2025-international-conference-demonstrating-commitment-to-advancing-research-in-pulmonary-arte/

2. Campbell P. FDA Approves Sotatercept (Winrevair) for Pulmonary Arterial Hypertension. HCPLive. March 26, 2024. Accessed June 12, 2025. https://www.hcplive.com/view/fda-approves-sotatercept-winrevair-for-pulmonary-arterial-hypertension

3. Humbert M, McLaughlin VV, Badesch DB, et al. Sotatercept in Patients with Pulmonary Arterial Hypertension at High Risk for Death. N Engl J Med 2025;392:1987-2000. doi:10.1056/NEJMoa2415160