Ryan Tedford Shares Insights About Sotatercept and Findings From the CADENCE Trial

Combined post-capillary pulmonary hypertension (CPC-PH) sits at one of cardiology's most challenging intersections—where pulmonary and cardiac disease converge in ways that have long defied effective treatment. Pharmacy Times spoke with Ryan Tedford, MD, at the 2026 American College of Cardiology meeting to discuss the CADENCE trial (NCT04945460), the rationale for studying sotatercept (Winrevair; Merck) in this population, and what the results may mean for the future of PH treatment.

Pharmacy Times: CPC-PH sits at a complex intersection of pulmonary and cardiac disease. What makes this condition so difficult to diagnose and treat?

Ryan Tedford, MD: One key consideration in making any diagnosis is having a treatment available for it. While many patients have been suspected of having pulmonary hypertension, if their pre-test probability of left heart disease was high, there wasn't necessarily a strong clinical need to pursue a formal CPC-PH diagnosis. Once we have an effective therapy for CPC-PH, I expect we'll see more diagnoses made. I draw a parallel to the field of amyloidosis—before we had treatment options, it was rarely diagnosed; once treatment arrived, diagnosis became far more routine.

In terms of treatment, many studies evaluating PH-specific drugs in CPC-PH have failed. They haven't reduced pulmonary vascular resistance or improved outcomes. There are several possible reasons for this. There is some overlap with Group 1 pulmonary hypertension in terms of pulmonary artery remodeling and genetic factors, but there are also key differences—notably the absence of intimal fibrosis and plexiform lesions and the presence of a strong vasoconstrictive functional component in CPC-PH. On top of that, we have the underlying heart failure to consider. Reducing pulmonary vascular resistance could theoretically flood the left side of the heart, raising filling pressures and precipitating pulmonary edema. So, there are many moving parts.

Pharmacy Times: Sotatercept is already approved in pulmonary arterial hypertension. What was the rationale for exploring it in CPC-PH specifically?

Tedford: Sotatercept is a significant advancement for pulmonary arterial hypertension across the spectrum of disease severity. As I mentioned, PH-specific therapies in Group 2 have not decreased pulmonary vascular resistance or improved outcomes. But the mechanism of sotatercept is quite different from prior agents. We believe it promotes pulmonary vascular remodeling and has a decongestion effect—it's not a typical pulmonary vasodilator. That distinction gave us reason to believe it might succeed where others have not.

Pharmacy Times: What were the most compelling findings from CADENCE, and what do they tell us about the mechanism in this setting?

Tedford: In CADENCE, we observed a statistically significant reduction in pulmonary vascular resistance—an effect that was even more pronounced when adjusted for changes in hemoglobin. Importantly, this translated into improved right ventricular function, as measured by RV-PA coupling via the TAPSE-to-PASP ratio. We also saw improvements in natriuretic peptides, which correlated with gains in functional capacity—including 6-minute walk distance and New York Heart Association class—as well as prolonged time to clinical worsening in patients randomized to sotatercept. The latter are exploratory endpoints, but they are nonetheless very promising.

In a population that tends to be older with more comorbidities than classic PAH patients, we were very encouraged by the safety profile. There were no excess adverse events compared to placebo. Importantly, we did not see excess bleeding — notable given that 75% of patients were on some form of anticoagulation. We also did not observe the development of intrapulmonary shunts or pericardial effusions. Overall, the safety profile was in line with what we had hoped for.

Pharmacy Times: How did the safety profile look in this population, which tends to be older and with more comorbidities than classic PAH patients?

Tedford: We were very pleased with the safety profile. There were no excess adverse events with sotatercept compared to placebo. Importantly, we did not see excess bleeding—which is notable given that 75% of patients were on some form of anticoagulation. We also did not observe the development of intrapulmonary shunts or pericardial effusions. Overall, the safety profile was in line with what we had hoped for.

Pharmacy Times: Does CADENCE open the door for exploring sotatercept across other forms of pulmonary hypertension or heart failure?

Tedford: Absolutely. It raises the question of whether patients with heart failure with reduced ejection fraction and CPC-PH might also benefit from a therapy like this. One notable finding in this study was a reduction in LV filling pressures and left atrial volume—suggesting that sotatercept's effects extend beyond the pulmonary vasculature to the myocardium itself, which is consistent with some of our preliminary data. And of course, it raises the question of whether this drug could be helpful in other forms of pulmonary hypertension, such as Group 3. There is a lot more to explore.