Sotatercept Demonstrates Significant Reduction in Morbidity and Mortality Across Broader PAH Risk Groups

At the American Heart Association Scientific Sessions 2025 in New Orleans, Vallerie McLaughlin, MD, discussed new findings inspired by the ZENITH study, which examined hard clinical events such as mortality, major morbidity, lung transplantation, and hospitalization in patients with pulmonary arterial hypertension (PAH). In ZENITH, investigators observed an improvement in that composite endpoint among very high-risk patients.

In her presentation, McLaughlin highlighted a new pooled analysis that expanded upon those findings by evaluating lower-risk populations from the PULSAR and STELLAR studies. This broader analysis included patients spanning a wide range of risk categories—more than half of whom were classified as low or intermediate-low risk.

Results showed a 75% reduction in the risk of major morbidity or mortality, with the benefit observed early in the course of treatment. McLaughlin emphasized that these results provide important evidence supporting the consideration of sotatercept across a broader range of PAH patient risk profiles.

Pharmacy Times: Looking at the pooled WINREVAIR data in pulmonary arterial hypertension, what key safety considerations should pharmacists keep in mind when monitoring patients—especially those on prostacyclin background therapy or antithrombotic agents?

Vallerie McLaughlin, MD: So, when we treat patients with PAH, we always have to consider risks and benefits. Monitoring safety is very important. We know that sotatercept, when reversed, can affect hemoglobin and platelet count, and the FDA requires us to monitor a CBC prior to each of the first 5 doses. That’s very important.

Some of the other side effects we see are bleeding, which tends to be minor bleeding, and what we call telangiectasias—these are little red spots on the skin. We need to monitor our patients for those as well.

Pharmacy Times: How do the ZENITH findings expand on what we’ve learned from the PULSAR and STELLAR trials regarding WINREVAIR’s long-term efficacy and clinical relevance?

McLaughlin: So, the findings that were presented today were really incited by the ZENITH study, which looked at hard events—the endpoint of mortality or major morbidity that included lung transplantation and hospitalization. In ZENITH, we found an improvement in that composite endpoint in patients who were very high risk.

What we did today was look at the lower-risk populations of PULSAR and STELLAR in addition. In this pooled population, these patients represented a very broad risk category. In fact, more than half of them were either low or intermediate-low risk.

There was also a 75% risk reduction in that hard endpoint of major morbidity or mortality, and the benefit was seen early in the course of treatment. I think this is very important evidence to use as we consider therapies for our PAH patients.