Sotatercept for Combined Post- and Pre-capillary Pulmonary Hypertension Associated With Heart Failure: Results from the Phase 2, Randomized, Placebo-Controlled CADENCE Study

Authors

• Mardi Gomberg-Maitland, George Washington University School of Medicine and Health Sciences, Washington, DC.
• Ryan J. Tedford, Medical University of South Carolina, Division of Cardiology, Department of Medicine, Charleston, SC.
• David Langleben, Center for Pulmonary Vascular Disease, Azrieli Heart Center, Jewish General Hospital, McGill University, Montreal, Quebec, Canada.
• Stephan Rosenkranz, Cologne University Hospital - Heart Center, Department of Cardiology and Cologne Cardiovascular Research Center Cologne, Germany.
• Barry Miller, Merck & Co., Inc., Rahway, NJ.
• Aaron D. Jones, Merck & Co., Inc., Rahway, NJ.
• Alessia Urbinati, Merck & Co., Inc., Rahway, NJ.
• Ciaran J. McMullan, Merck & Co., Inc., Rahway, NJ.
• Alexandra G. Cornell, Merck & Co., Inc., Rahway, NJ.
• Jean-Luc Vachiery, Hopital Universitaire de Bruxelles Erasme, Cardiology, Brussels, Belgium.

Document Type

Journal Article

Publication Date

3-29-2026

Journal

Circulation

DOI

10.1161/CIRCULATIONAHA.126.079918

Abstract

BACKGROUND: Combined post- and pre-capillary pulmonary hypertension in heart failure with preserved ejection fraction (CpcPH-HFpEF) involves remodeling in both the heart and pulmonary vasculature. Despite significant mortality, there are no proven therapies. METHODS: In this multicenter, randomized, placebo-controlled, phase 2 trial, adults received sotatercept (0.3 or 0.7 mg/kg) or placebo every 3 weeks. The primary end point was change in pulmonary vascular resistance at week 24. Hodges-Lehmann shift estimates described placebo-adjusted changes. RESULTS: 164 patients were randomized 54:55:55 to sotatercept 0.3 mg/kg, 0.7 mg/kg, and placebo, and baseline median pulmonary vascular resistance was 5.2 (interquartile range [IQR] 4.0-6.9) Wood units. The median change from baseline in pulmonary vascular resistance at week 24 was -0.67 Wood units in the sotatercept 0.3 mg/kg group, -0.33 Wood units in the sotatercept 0.7 mg/kg group, and 0.26 Wood units in the placebo group. The Hodges-Lehmann shift estimates in pulmonary vascular resistance were -1.02 Wood units (95% CI, -1.81 to -0.23; P=0.004) for 0.3 mg/kg and -0.75 Wood units (95% CI, -1.52 to 0.03; P=0.024) for 0.7 mg/kg sotatercept. Reductions were observed in mean pulmonary arterial pressure (0.3 and 0.7 mg/kg: -9.19 mm Hg [95% CI, -13.00 to -5.38] and -9.22 [95% CI, -12.97 to -5.46]) and pulmonary arterial wedge pressure (0.3 and 0.7 mg/kg: -3.04 mm Hg [95% CI, -5.77 to -0.32] and -2.53 [95% CI, -5.33 to 0.28]). Changes in 6-minute walk distance were 20.3 meters (95% CI, 1.5-39.1) for 0.3 mg/kg and 5.8 meters (95% CI, -17.3 to 28.9) for 0.7 mg/kg sotatercept. The most common adverse events with sotatercept (both groups) were increased hemoglobin and diarrhea. CONCLUSIONS: These findings provide proof of concept for improved pulmonary vascular and cardiac hemodynamics following activin signalling inhibition with sotatercept in patients with CpcPH-HFpEF.

APA Citation

Gomberg-Maitland, Mardi; Tedford, Ryan J.; Langleben, David; Rosenkranz, Stephan; Miller, Barry; Jones, Aaron D.; Urbinati, Alessia; McMullan, Ciaran J.; Cornell, Alexandra G.; and Vachiery, Jean-Luc, "Sotatercept for Combined Post- and Pre-capillary Pulmonary Hypertension Associated With Heart Failure: Results from the Phase 2, Randomized, Placebo-Controlled CADENCE Study" (2026). GW Authored Works. Paper 8812.
https://hsrc.himmelfarb.gwu.edu/gwhpubs/8812

Department

Medicine