Mavacamten in Adolescents with Obstructive Hypertrophic Cardiomyopathy

BACKGROUND: Approved pharmacologic therapies for pediatric hypertrophic cardiomyopathy are lacking, and surgical intervention may be indicated in patients with left ventricular outflow tract obstruction. The efficacy and safety of mavacamten, a cardiac myosin inhibitor that is available for adults, warrant evaluation in adolescents. METHODS: We conducted a phase 3, double-blind, randomized, placebo-controlled trial involving symptomatic adolescents (12 to <18 years of age) with New York Heart Association class II or III obstructive hypertrophic cardiomyopathy. The patients were randomly assigned in a 1:1 ratio to receive mavacamten or placebo. The primary end point was the change from baseline to week 28 in left ventricular outflow tract pressure gradient provoked by the Valsalva maneuver. RESULTS: A total of 44 patients underwent randomization; 23 patients (8 [35%] of whom were female) were assigned to mavacamten group, and 21 (5 [24%] of whom were female) were assigned to the placebo group. The mean (±SD) age of the patients was 14.7±1.7 years in the mavacamten group and 14.6±1.7 years in the placebo group, and the mean Valsalva left ventricular outflow tract gradient at baseline was similar in the two groups (78.4±34.1 mm Hg and 80.8±47.4 mm Hg, respectively). At week 28, the least-squares mean change in the Valsalva left ventricular outflow tract gradient was -48.5 mm Hg in the mavacamten group and -0.5 mm Hg in the placebo group (difference, -48.0 mm Hg; 95% confidence interval, -67.7 to -28.3; P<0.001). The incidence of adverse events was similar in the two groups. Two patients in each group had serious adverse events; in the mavacamten group, 1 patient had two episodes of syncope, and another had an inappropriate shock delivered by an implantable cardioverter-defibrillator; in the placebo group, 1 patient had chest pain, and another had depression with suicidal ideation. No patient had a reduction in the left ventricular ejection fraction to less than 50%. No deaths occurred during the trial. CONCLUSIONS: Among adolescent patients with obstructive hypertrophic cardiomyopathy, the reduction in left ventricular outflow tract obstruction was significantly greater with mavacamten than with placebo over a 28-week period. (Funded by Bristol Myers Squibb; SCOUT-HCM ClinicalTrials.gov number, NCT06253221.).