A recent global clinical trial involving The Hospital for Sick Children demonstrated that mavacamten—previously approved for adults—can safely improve blood flow in adolescents with Hypertrophic Cardiomyopathy (HCM). The findings, published in the New England Journal of Medicine, represent the first phase III randomized, double-blind, placebo-controlled study conducted specifically in young patients with HCM, the most common inherited cardiac disorder in children and adolescents.¹

Currently, treatment options for paediatric HCM focus largely on symptom control using beta-blockers or calcium channel blockers. However, these therapies do not address the underlying disease mechanism, and many patients ultimately require invasive interventions such as septal reduction surgery to relieve left ventricular outflow obstruction.² According to senior investigator of the trial, these results represent a significant advancement in precision medicine for paediatric cardiology, with the potential to reduce the need for open-heart surgery in affected children.¹

The foundation for this trial originated from laboratory research using patient-derived induced pluripotent stem cells, which were differentiated into cardiomyocytes to model HCM. These studies demonstrated that mavacamten, a selective cardiac myosin inhibitor, improved myocardial relaxation and reduced hypercontractility across multiple genetic variants of the disease.³ These preclinical findings supported progression to the multinational SCOUT-HCM phase III clinical trial.

The SCOUT-HCM trial enrolled 44 adolescents aged 12–18 years across nine countries who continued to experience symptoms despite standard therapy. After 28 weeks, participants treated with mavacamten showed significant reductions in left ventricular outflow tract obstruction compared with placebo. Additional benefits included improved exercise capacity, decreased ventricular wall thickness, improved symptoms, and reduced cardiac stress markers.¹ Importantly, no participants experienced significant deterioration in cardiac function, a concern previously observed in some adult trials.

Participants will continue to be followed for three years to evaluate long-term safety and durability of response. These findings highlight the potential for disease-modifying therapy in paediatric HCM and demonstrate the successful translation of laboratory discoveries into clinical benefit for children worldwide.^1,3

References:

1- Mital S, Jeewa A, et al. Mavacamten in adolescents with symptomatic obstructive hypertrophic cardiomyopathy (SCOUT-HCM). N Engl J Med. 2026

2- Ommen SR, Mital S, Burke MA, et al. Hypertrophic cardiomyopathy: clinical management and treatment strategies. Circulation. 2020;142:e558-e631.

3- Mital S, et al. Patient-derived cardiomyocyte models identify therapeutic effects of mavacamten in paediatric hypertrophic cardiomyopathy. Nat Med. 2024;30