CONFERENCE UPDATE: ACC 2026

The phase 3 SCOUT-HCM trial shows mavacamten significantly improves LVOT obstruction in adolescents with HCM

CARDIOLOGY
29 Jun 2026

STUDY DESIGN

Mavacamten, a selective cardiac myosin inhibitor approved for adults with symptomatic obstructive hypertrophic cardiomyopathy (HCM), has not previously been studied in a pediatric cohort.1 SCOUT-HCM is a phase 3, randomized, double-blind, placebo-controlled trial, designed to evaluate the efficacy and safety of mavacamten in adolescents with symptomatic obstructive HCM.1 The study enrolled 44 patients aged 12 to <18 years with a confirmed diagnosis of HCM.1 Eligible participants were required to have a Valsalva left ventricular outflow tract (LVOT) gradient ≥30mmHg, a maximal LVOT gradient ≥50mmHg, a left ventricular ejection fraction (LVEF) ≥60%, and New York Heart Association (NYHA) class II-III symptoms.1

Patients were randomized 1:1 to receive mavacamten once daily or a matching placebo during a 28-week treatment period.1 Weight-based dosing was used at study initiation, with patients receiving either 5mg daily (body weight ≥45kg) or 2.5mg daily (body weight ≥35kg to <45kg).1 Dose adjustments were permitted during the trial, with potential down-titration to 1mg and up-titration to 15mg based on clinical and echocardiographic parameters.1 Baseline characteristics were generally balanced between groups, including age, mutations, LVOT gradient, and background beta-blocker therapy.1 Baseline biomarker levels were higher in the mavacamten group, with median NT proBNP 1,776pg/mL vs. 1,294pg/mL in the placebo group, high-sensitivity cardiac troponin I (hs-cTnI) 36.1pg/mL vs. 22.7pg/mL, and high-sensitivity cardiac troponin T (hs-cTnT) of 25.3pg/mL vs. 16.7pg/mL.1

The primary endpoint was the change from baseline to week 28 in Valsalva LVOT gradient.1 Secondary efficacy endpoints included changes in resting and post-exercise LVOT gradients, maximal left ventricular (LV) wall thickness, E/e’ ratio, and symptom burden measured by the HCM Symptom Questionnaire Shortness of Breath (HCMSQ SoB) domain.1 Additional analyses evaluated the proportion of patients achieving maximal LVOT gradient reduction to <30mmHg, improvement of ≥1 NYHA class, improvement of ≥1 mitral regurgitation grade, or increased peak oxygen consumption.1 Safety endpoints included the incidence of treatment-emergent adverse events (TEAEs), treatment-emergent serious adverse events (TESAEs), reductions in LVEF <50% or ≤30%, and changes in QT interval on electrocardiography.1

FINDINGS

Primary endpoint:
  • The primary endpoint was the change from baseline to week 28 in Valsalva LVOT gradient1
  • Mavacamten significantly reduced Valsalva LVOT gradient vs. placebo over 28 week, with the least squares (LS) mean difference of -48.0mmHg (29.0mmHg vs. 72.7mmHg; 95% CI: -67.7 to -28.3; p<0.0001), bringing LVOT gradients below the guideline-defined obstruction threshold1

Secondary endpoints:
  • Secondary endpoints included changes in resting and post exercise LVOT gradients, maximal left ventricular wall thickness, E/e’ ratio, and symptom burden measured by the HCMSQ SoB domain score1
  • Additional analyses evaluated the proportion of patients achieving maximal LVOT gradient reduction to <30mmHg, improvement of ≥1 NYHA class, improvement of ≥1 mitral regurgitation grade, or increased peak oxygen consumption1
  • Mavacamten significantly reduced both resting and post-exercise LVOT gradients vs. placebo, with LS mean differences of -47.0mmHg (95% CI: -62.7 to -31.4; p<0.0001) and -41.7mmHg (95% CI: -59.7 to -23.7; p<0.0001), respectively, lowering resting gradient below the guideline-defined obstruction threshold1
  • Mavacamten demonstrated significant structural improvements with a reduction in maximal LV wall thickness (LS mean difference -1.8mm; 95% CI: -3.4 to -0.2; p=0.0269) and improved diastolic function as reflected by a lower average E/e’ ratio (LS mean difference -3.4; 95% CI: -5.1 to -1.6; p=0.0002)1
  • Mavacamten was associated with a significantly higher proportion of patients achieving reduction of maximal LVOT gradient to <30mmHg (65.2% vs. 4.8%; 95% CI: 35.1-78.1; p<0.0001), improvement of ≥1 mitral regurgitation grade (39.1% vs. 4.8%; 95% CI: 10.7-55.9; p=0.0072), and improvement ≥1 NYHA class (43.5% vs. 9.5%; 95% CI: 8.0-56.3; p=0.0125)1
  • Mavacamten reduced biomarkers of myocardial stress and injury vs. placebo, including NT-proBNP, hs-cTnI, and hs-cTnT, with ratios to baseline of 0.23 (95% CI: 0.14-0.37), 0.37 (95% CI: 0.23-0.60), and 0.55 (95% CI: 0.38-0.79), respectively1

Safety:
  • TEAEs occurred in 78.3% of patients receiving mavacamten vs. 81.0% receiving placebo, while TESAEs were reported in 8.7% and 9.5% of patients, respectively1
  • No TEAE-related discontinuations or deaths were reported, and no patients experienced LVEF <50% or ≤30%, atrial fibrillation, or symptomatic heart failure1

 

“Mavacamten demonstrates clinically meaningful and statistically significant reductions in Valsalva LVOT gradient, alongside broad improvements in obstruction, symptoms, and cardiac function, supporting its role for symptomatic obstructive HCM in adolescents.”

 

Dr. Joseph Rossano
Children’s Hospital of Philadelphia, Pennsylvania, United States

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