Mavacamten treatment for obstructive hypertrophic cardiomyopathy a clinical trial

Background: Mavacamten, an orally administered, small-molecule modulator of cardiac myosin, targets underlying bio-mechanical abnormalities in obstructive hypertrophic cardiomyopathy (oHCM). Objective: To characterize the effect of mavacamten on left ventricular outflow tract (LVOT) gradient. Design: Open-label, nonrandomized, phase 2 trial. (Clinical Trials.gov: NCT02842242) Setting: 5 academic centers. Participants: 21 symptomatic patients with oHCM. Intervention: Patients in cohort A received mavacamten, 10 to 20 mg/d, without background medications. Those in cohort B received mavacamten, 2 to 5 mg/d, with -blockers allowed. Measurements: The primary end point was change in postexercise LVOT gradient at 12 weeks. Secondary end points included changes in peak oxygen consumption (pVO₂), resting and Valsalva LVOT gradients, left ventricular ejection fraction (LVEF), and numerical rating scale dyspnea score. Results: In cohort A, mavacamten reduced mean postexercise LVOT gradient from 103 mm Hg (SD, 50) at baseline to 19 mm Hg (SD, 13) at 12 weeks (mean change, 89.5 mm Hg [95% CI, 138.3 to 40.7 mm Hg]; P = 0.008). Resting LVEF was also reduced (mean change, 15% [CI, 23% to 6%]). Peak VO₂ increased by a mean of 3.5 mL/kg/min (CI, 1.2 to 5.9 mL/kg/ min). In cohort B, the mean postexercise LVOT gradient decreased from 86 mm Hg (SD, 43) to 64 mm Hg (SD, 26) (mean change, 25.0 mm Hg [CI, 47.1 to 3.0 mm Hg]; P = 0.020), and mean change in resting LVEF was 6% (CI, 10% to 1%). Peak VO₂ increased by a mean of 1.7 mL/kg/min (SD, 2.3) (CI, 0.03 to 3.3 mL/kg/min). Dyspnea scores improved in both cohorts. Mavacamten was well tolerated, with mostly mild (80%), moderate (19%), and unrelated (79%) adverse events. The most common adverse events definitely or possibly related to mavacamten were decreased LVEF at higher plasma concentrations and atrial fibrillation. Limitation: Small size; open-label design. Conclusion: Mavacamten can reduce LVOT obstruction and improve exercise capacity and symptoms in patients with oHCM.