Key result
Mavacamten reduces LVOT obstruction vs placebo in adolescents with obstructive HCM.
Why the trial?
The trial was conducted to evaluate the efficacy and safety of mavacamten in adolescents with obstructive hypertrophic cardiomyopathy, addressing the lack of approved pharmacologic therapies for pediatric patients and the need for alternatives to surgical intervention.
Does mavacamten reduce left ventricular outflow tract pressure gradient in symptomatic adolescents with obstructive hypertrophic cardiomyopathy?
RCT (n=44)
Double-blind
1:1
Does mavacamten reduce left ventricular outflow tract pressure gradient in symptomatic adolescents with obstructive hypertrophic cardiomyopathy?
Mean Difference: -48 (95% CI -67.7–-28.3)
Absolute Event Rate: -48.5% vs -0.5%
p-value: p=<0.001
Mavacamten significantly reduces the left ventricular outflow tract pressure gradient compared to placebo in symptomatic adolescents with obstructive hypertrophic cardiomyopathy.
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The first positive Phase 3 trial of mavacamten in adolescents with obstructive HCM is being read as a potential practice-changer for pediatric cardiology, with the lead investigator calling it a transformative advance in a field that currently has no approved therapies for this age group.
Reaction to SCOUT-HCM is uniformly positive, with experts framing the trial as a landmark for pediatric cardiology given the near-total absence of randomized, controlled evidence in adolescent obstructive HCM. The trial's lead investigator emphasizes not only symptom relief but early signs of favorable cardiac remodeling. The open question is whether the FDA will grant a pediatric indication and how this might shift the field away from surgery-first approaches in teens.
Whether the FDA will approve mavacamten for adolescents and how quickly it might enter pediatric guidelines remains to be seen. Longer-term data on whether the remodeling signal translates into durable changes in disease trajectory have not yet been established.
“These results, which are from one of the few prospective randomized trials of medical therapy for cardiovascular disease in childhood, support the use of mavacamten as an efficacious treatment option for symptomatic obstructive HCM in adolescent patients.”
Rossano, who has cared for children with obstructive HCM for decades, says treatment options have been limited to symptom-focused medications or invasive surgery. He calls the results very encouraging, noting obstruction reduction was dramatic and comparable to or greater than what was seen in adults. Beyond symptom relief, he highlights a signal of favorable cardiac remodeling that could improve the natural history of the disease, calling the trial a significant advance and one of the very few positive Phase 3 randomized controlled trials in pediatric cardiology.
Supports mavacamten in adolescents with obstructive HCM; extends adult RCT evidence to this pediatric population.
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.).
Journal, society, and media accounts. Useful signal, not independent expert judgment.
Rossano et al. (2026) conducted an RCT in Obstructive hypertrophic cardiomyopathy (n=44). Mavacamten vs. Placebo was evaluated on Change from baseline to week 28 in left ventricular outflow tract pressure gradient provoked by the Valsalva maneuver (MD -48.0 mm Hg, 95% CI -67.7 to -28.3, p=<0.001). Mavacamten significantly reduced the Valsalva left ventricular outflow tract gradient compared to placebo over 28 weeks (difference, -48.0 mm Hg; 95% CI, -67.7 to -28.3; P<0.001).
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