CADENCE: Sotatercept Reduces PVR in CpcPH-HFpEF, With Mardi Gomberg-Maitland, MD, MSc

Sotatercept has reduced pulmonary vascular resistance (PVR) in combined post- and pre-capillary pulmonary hypertension (CpcPH) heart failure with preserved ejection fraction (HFpEF), improving both pulmonary vascular and cardiac end points, according to data from the CADENCE trial.1,2

These data were presented at the American College of Cardiology (ACC) Scientific Sessions 2026 in New Orleans, Louisiana, by Mardi Gomberg-Maitland, MD, MSc, director of the pulmonary hypertension program, chief clinical research officer at the Office of Clinical Research SMHS, and professor of medicine at George Washington University.

“Here we have a drug for a disease that we’ve never had therapy for, one that has high morbidity and mortality, and now we have potential,” Gomberg-Maitland told HCPLive in an exclusive interview. “We’re seeing good effects – now it’s time that we move to the next phase, to phase 3.”

CADENCE is an ongoing phase 2, multicenter, double-blind, randomized trial investigating the efficacy, safety, and tolerability of sotatercept in patients with CpcPH-HFpEF. The trial consisted of a 24-week placebo-controlled treatment period and an active-drug extension period. Gomberg-Maitland and colleagues reported the placebo-controlled period, during which patients were randomly assigned in a 1:1:1 ratio to receive subcutaneous sotatercept at 0.3 mg/kg (before potential escalation to 0.7 mg/kg after 3 dosing visits) or placebo every 3 weeks.2

Eligible patients were aged 18-85 years with symptomatic CpcPH-HFpEF diagnosed via an assessment of hemodynamics through right heart catheterization. Patients were excluded if they were diagnosed with another form of pulmonary hypertension, clinically significant lung disease, severe hepatic impairment, and/or cirrhosis, among other criteria.2

CADENCE’s primary efficacy endpoint was the change from baseline in PVR at week 24. The key secondary efficacy endpoint was the change from baseline in 6-meter walk distance at week 24. Other secondary endpoints included time to clinical worsening, which was defined as the time from the first dose date to the first occurrence of all-cause death or non-elective hospitalization for cardiopulmonary indications related to pulmonary hypertension and/or heart failure, and change from baseline in N-terminal pro-B-type natriuretic peptide (NT-proBNP) levels, NYHA functional class, and hemodynamic or echocardiographic parameters.2

A total of 164 patients were randomized, with 54 assigned to sotatercept 0.3 mg/kg, 55 assigned to 0.7 mg/kg escalated from 0.3, and 55 assigned to placebo. The median duration of follow-up during this period was 5.6 months (interquartile range [IQR], 5.5-5.7) in the 0.3 mg/kg group, 5.6 months (IQR, 5.5-5.8) in the 0.7 mg/kg group, and 5.6 months (IQR, 5.5-5.8) in the placebo group.2

By week 24, sotatercept treatment resulted in substantially greater reductions in PVR versus placebo. The median change from baseline was -0.67 Wood units in the 0.3 mg/kg group, -0.33 Wood units in the 0.7 mg/kg group, and 0.26 Wood units in the placebo group. The Hodges-Lehmann shift estimate was -1.02 Wood units (95% CI, -1.81 to -0.23; P = .004) for the 0.3 mg/kg group and -0.75 Wood units (95% CI, -1.52 to 0.03; P = .024) for the 0.7 mg/kg group compared to placebo. These results were consistent across subgroups, including the degree of PVR elevation at baseline.2

Mean pulmonary arterial pressure saw a mean reduction of -9.19 mmHg (95% CI, -13 to -5.38) and -9.22 (95% CI, -12.97 to -5.46) in the 0.3 mg/kg and 0.7 mg/kg groups, respectively. Changes in 6-minute walk distance were 20.3 meters (95% CI, 1.5 to 39.1) for the 0.3 mg/kg group and 5.8 meters (95% CI, -17.3 to 28.9) for the 0.7 mg/kg group.2

Ultimately, Gomberg-Maitland and colleagues noted that these findings provide an effective proof of concept for improved pulmonary vascular and cardiac hemodynamics following activin signaling inhibition with sotatercept in patients with CpcPH-HFpEF.1

“As for how it can impact therapy, we’re going to continue into our phase 3 trials to really look at these echo parameters over time and see if this is perhaps a way that we can follow patients,” Gomberg said. “Ultimately, you don’t want to be doing right heart casts on everybody to see how they’re doing. We need other assessments that are more functional.”

Editors’ Note: Gomberg-Maitland reports disclosures with Merck, Catalys Pacific, Gossamer, Janssen Pharmaceuticals, Medtronic, Novartis, and others.

References

1. Gomberg-Maitland M, Tedford R, Langleben D, et al. Efficacy and Safety of Sotatercept in Combined Post- and Pre-capillary Pulmonary Hypertension Associated With Heart Failure With Preserved Ejection Fraction: results from the Phase 2 Cadence Trial. Abstract presented at the American College of Cardiology Scientific Sessions 2026, New Orleans, Louisiana. March 28-30, 2026.

2. Gomberg-Maitland M, Tedford RJ, Langleben D, et al. Sotatercept for combined post- and pre-capillary pulmonary hypertension associated with heart failure: Results from the phase 2, randomized, placebo-controlled Cadence Study. Circulation. Published online March 29, 2026. doi:10.1161/circulationaha.126.079918