Drug Approval for Painful Heart Condition Expands to Kids

The FDA expanded its approval of mavacamten (Camzyos) to include children with symptomatic obstructive hypertrophic cardiomyopathy (HCM).

Mavacamten thus becomes the first cardiac myosin inhibitor indicated for pediatric patients weighing at least 30 kg (~66 lbs) as a treatment to improve functional capacity and symptoms. Mavacamten was initially approved for adults with obstructive HCM in 2022.

Approval for pediatric patients was based on the phase III SCOUT-HCM randomized trial in which mavacamten showed efficacy by reducing left ventricular outflow tract (LVOT) obstruction over 28 weeks.

“The FDA approval of Camzyos for pediatric patients with symptomatic obstructive hypertrophic cardiomyopathy represents a landmark moment for pediatric cardiology. For the first time, children with this serious condition have a therapy that is FDA-approved to reduce [LVOT] obstruction,” said Joseph Rossano, MD, SCOUT-HCM investigator at Children’s Hospital of Philadelphia, in a press release from maker Bristol Myers Squibb.

SCOUT-HCM enrolled 44 adolescents who had left ventricular ejection fraction (LVEF) ≥60%, Valsalva LVOT peak gradient ≥30 mmHg and a maximal gradient ≥50 mmHg at rest or with provocation, and who were on background therapy with a beta blocker, calcium channel blocker, and/or disopyramide.

With mavacamten, there was a significant improvement in Valsalva LVOT gradient of -48.0 mm Hg from baseline to week 28 compared with placebo (P<0.0001). There were also improvements in obstruction severity at rest, diastolic function, cardiac hypertrophy, maximal left ventricular wall thickness, average E/e’ ratio, and markers of cardiac stress and myocardial injury, Rossano’s group reported.

These results prompted Rossano to suggest in March that cardiac myosin inhibitor therapy could ultimately change the natural history of pediatric obstructive HCM.

Pediatric HCM is a rare and genetically inherited cardiovascular condition, characterized by left ventricular hypertrophy in the absence of another cardiac, systemic, or metabolic disease. Pharmacological treatments have historically been limited and unproven in this population.

“I cannot help but think back to my 12-year-old self receiving my diagnosis and being told there were no treatment options approved specifically for my disease,” said Lisa Salberg, CEO and founder of the Hypertrophic Cardiomyopathy Association, in a statement. “Having a targeted therapy for cardiac myosin is a significant breakthrough, and it’s a welcome change to bring this approval to a younger population.”

In adults and children alike, mavacamten is available only through a restricted Risk Evaluation and Mitigation Strategy program due to the risk of heart failure caused by systolic dysfunction. Its label warns against use in people with heart failure and lists concurrent use with certain CYP2C19 or CYP3A4 medications as contraindications.

No safety signals emerged for mavacamten use among adolescents in the SCOUT-HCM trial. There were no LVEF dips below 50% and no cases of atrial fibrillation, symptomatic heart failure, or death.

Another cardiac myosin inhibitor for symptomatic obstructive HCM, aficamten (Myqorzo), remains indicated only for adults.