Mavacamten Poised to Expand to Pediatric Obstructive Hypertrophic Cardiomyopathy

NEW ORLEANS — The benefit of mavacamten (Camzyos) held up in symptomatic adolescents with obstructive hypertrophic cardiomyopathy (HCM), the phase III SCOUT-HCM trial showed.

Already available to adults, the cardiac myosin inhibitor led to reductions in left ventricular outflow tract (LVOT) obstruction, with a mean difference in change in Valsalva LVOT gradient of -48.0 mm Hg from baseline to week 28 compared with the placebo group (P<0.0001), reported Joseph Rossano, MD, of the Children's Hospital of Philadelphia, at the American College of Cardiology (ACC) annual meeting.

There were also broad improvements in obstruction severity at rest (mean difference in LVOT gradient -47.0 mm Hg, P<0.0001) and post-exercise (-41.7 mm Hg, P<0.0001), diastolic function, cardiac hypertrophy, New York Heart Association (NYHA) class, and mitral valve dysfunction.

The study was simultaneously published in the New England Journal of Medicine.

“These results, from one of the few RCTs [randomized clinical trials] in cardiology of a targeted pharmacological therapy in adolescents, support the use of mavacamten as an efficacious treatment option for symptomatic obstructive HCM in adolescent patients,” Rossano concluded.

HCM is a heart muscle disease that is characterized by left ventricular hypertrophy in the absence of another cardiac, systemic, or metabolic disease. Over 300,000 patients in the U.S. have reportedly been diagnosed with HCM, half of them with obstructive disease, making HCM the most common inherited cardiovascular disease.

Mavacamten won FDA approval for symptomatic obstructive HCM in adults in 2022. A second cardiac myosin inhibitor, aficamten (Myqorzo), was approved at the end of 2025. Both are available only through a restricted Risk Evaluation and Mitigation Strategy program due to the risk of heart failure caused by systolic dysfunction.

In SCOUT-HCM, there were no apparent safety signals with mavacamten in adolescents. Treatment-related adverse events were comparable between groups; no patient experienced left ventricular ejection fraction (LVEF) dips below 50% and there were no cases of atrial fibrillation, symptomatic heart failure, or death.

After 28 weeks on mavacamten, Valsalva and resting LVOT gradients had fallen to 29.0 mm Hg and 23.9 mm Hg on average, respectively, both going below the guideline criteria for obstruction with mavacamten, according to Rossano.

Beyond LVOT gradients, there were also improvements in maximal left ventricular wall thickness (mean difference -1.8 mm, P=0.0269) and average E/e’ ratio (-3.4, P=0.0002) with mavacamten. Additionally, the treatment reduced markers of cardiac stress and myocardial injury compared with placebo.

The expectation now is that mavacamten will become the first cardiac myosin inhibitor greenlit for adolescent patients.

“Pediatric HCM is a rare cardiac disorder that is associated with severe, sometimes life-threatening, symptoms,” Rossano said in a press release from drugmaker Bristol Myers Squibb. “With no approved therapies for pediatric patients with [obstructive] HCM and current recommendations for pharmacological therapy primarily extrapolated from evidence obtained from adult studies, the positive results of this trial represent a significant advance in the field of pediatric cardiology and the potential for a meaningful new therapy for adolescent patients if approved by the FDA.”

ACC session discussant Kenneth Margulies, MD, of the University of Pennsylvania in Philadelphia, called this a “lovely study that is surely going to change practice.”

Mavacamten and aficamten are already having a “transformative” impact in adults, Margulies said, suggesting that it would appear from the reduced left ventricular wall thickness in SCOUT-HCM that mavacamten has particular relevance for pediatric obstructive HCM.

Rossano agreed, noting that “one could imagine if these findings are sustained or improve over time, what a dramatic effect they could have on young people over the course of their lifetime.”

It could “change the natural history of the disease,” he added.

The double-blind international trial ultimately enrolled 44 adolescents with symptomatic obstructive HCM and a Valsalva LVOT gradient ≥30 mm Hg, a maximal LVOT gradient ≥50 mm Hg, an LVEF of at least 60%, and NYHA class II-III symptoms. Most patients were from the U.S. (66%). Median age was just under 15 years, about 30% were girls, and two in three were white.

Background therapy consisted of beta-blockers in most patients (over 80%); some were taking calcium channel blockers (around 11%) and disopyramide (about 20%).

Median baseline resting LVOT gradient was 65 mm Hg, median Valsalva LVOT gradient was 80 mm Hg, and maximal left ventricular wall thickness was around 26 mm.

Patients were randomized 1:1 to mavacamten (2.5 mg/day or 5 mg/day depending on body weight, with down- and up-titration possible) or placebo. After the study’s 28-week placebo-controlled phase came a 28-week period in which the placebo group crossed over to mavacamten; a final open-label long-term extension period is planned for another 144 weeks.

In the mavacamten group, one patient had a serious adverse event consisting of two syncope events, and another patient had an inappropriate implantable cardioverter-defibrillator shock delivered resulting in temporary interruption of mavacamten.

Major limitations to SCOUT-HCM included its small sample size and predominantly white population. The trial had also excluded children under 12 years old and those with phenocopies (e.g., Noonan syndrome), for whom mavacamten has plenty of potential, Rossano noted.

Of note, mavacamten failed to meet expectations among patients with symptomatic nonobstructive HCM in the ODYSSEY-HCM trial.