How Sotatercept Is Raising the Bar for PAH Treatment Goals

In an interview with Pharmacy Times, Vallerie McLaughlin, MD, professor of internal medicine at the University of Michigan School of Medicine, discussed the 2026 European Respiratory Society (ERS) guideline update incorporating sotatercept (Winrevair) into the pulmonary arterial hypertension (PAH) treatment algorithm. McLaughlin noted that the update gives the first-in-class activin signaling inhibitor a strong recommendation for patients who do not achieve low-risk status after initial dual oral or upfront triple combination therapy. Unlike traditional vasodilatory therapies, she explained, sotatercept appears to contribute to vascular and right ventricular remodeling, prompting more aggressive, long-term treatment goals.¹

Pharmacy Times: What makes the addition of sotatercept to the European Respiratory Society (ERS) treatment guidelines a meaningful moment for patients with pulmonary arterial hypertension (PAH)?

Vallerie McLaughlin, MD: Sotatercept (Winrevair; Merck) is a first-in-class activin signaling inhibitor that just became commercially available a couple of years ago, so it's new since the 2022 European Society of Cardiology (ESC)/ERS guidelines. There's now a wealth of data on sotatercept across various patient populations, including those with prevalent disease, those with very advanced disease, and even the more recently diagnosed patients. And so, the 2026 update allows for the inclusion of sotatercept into this evidence-based treatment algorithm. The ERS guidelines are highly reputable guidelines that are used all around the world, so helping place sotatercept in that treatment algorithm based on the data is a resource for many PAH physicians who treat these patients.

I think the 2026 update recognized the high quality of the evidence of sotatercept across these patient populations and gave it a very strong recommendation for patients who do not achieve low-risk status after that first step, whether it be dual oral therapy for the majority of the patients or upfront triple combination therapy with a parenteral prostacyclin in the high-risk patients. I think having that knowledge, having that written down, going through the evidence is very supportive for physicians taking care of patients with pulmonary arterial hypertension.

Pharmacy Times: How does targeting the activin signaling pathway change the way you think about treating PAH?

McLaughlin: It's a very interesting way to approach pulmonary hypertension, and it does something more than the other therapies that we have traditionally had. We traditionally had medications that worked more in a vasodilatory way, but sotatercept in the activin signaling pathway probably does some amount of vascular remodeling, and we're seeing more substantial changes in hemodynamics and right ventricular (RV) function than we have with more traditional therapies. We have good hemodynamic data suggesting about a 14 mm Hg reduction in mean pulmonary artery pressure, which is really clinically significant. And we have lots of echo data suggesting that the right ventricle shrinks and remodels.

While it is hard to define what disease modification really means, we do feel like we are modifying the disease in these patients. We're trying to get more patients into what we might call a partial remission—getting their hemodynamics to a state where it would improve their long-term outcome. I think the availability of sotatercept has kind of raised the bar on how we treat pulmonary arterial hypertension, and we now have more aggressive goals and think long-term about really modifying this disease.

REFERENCE

1. Halpern L. ERS adds sotatercept to pulmonary arterial hypertension treatment guidelines. Pharmacy Times. Published September 16, 2026. Accessed September 23, 2026. https://www.pharmacytimes.com/view/ers-adds-sotatercept-to-pah-treatment-guidelines