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Sotatercept for Combined Post- and Precapillary Pulmonary Hypertension Associated With Heart Failure: Results From
Mardi Gomberg-Maitland1, Ryan J Tedford2, David Langleben3
1Department of Medicine, Section of Cardiology, George Washington University School of Medicine and Health Sciences, Washington, DC (M.G-M.).
Background:
Combined post- and precapillary pulmonary hypertension in heart failure with preserved ejection fraction 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:
A total of 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, 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 m (95% CI, 1.5-39.1) for 0.3 mg/kg and 5.8 m (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 after activin signaling inhibition with sotatercept in patients with combined post- and precapillary pulmonary hypertension in heart failure with preserved ejection fraction.
Registration:
URL: https://www.clinicaltrials.gov; Unique identifier: NCT04945460.
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