Mavacamten, a first-in-class drug, was associated with a significant improvement in left ventricular outflow tract (LVOT) gradient compared to placebo in adolescent patients with obstructive hypertrophic cardiomyopathy (oHCM), based on results from the international, multicenter SCOUT-HCM study presented during a Late-Breaking Clinical Trial session at ACC.26 in New Orleans and simultaneously published in NEJM.

In the first mavacamten trial in adolescents, investigators Joseph William Rossano, MD, FACC, et al., randomized 43 symptomatic patients between the ages of 12-17 years with NYHA class II or III oHCM to 28 weeks of daily mavacamten (n=23) or placebo (n=20). Patients had activity-limited heart failure (HF) symptoms, peak LVOT gradients >50 mm Hg and LVEF >60%. The mean Valsalva LVOT gradient was similar in the two groups (78.4 and 80.8 mm Hg).

Results at week 28 showed a substantial improvement in the primary endpoint of change in Valsalva LVOT gradient, with an average drop of 48.5 mm Hg in the mavacamten group vs. 0.5 mm Hg in the placebo group (p<0.001). Those in the treatment arm compared with placebo also experienced improvements in the secondary endpoints: change in resting LVOT (–39.0 vs. 8.1), maximal LV wall thickness (–2.5 vs. –0.7), peak oxygen consumption and measures of symptoms such as fatigue and shortness of breath. Additionally, troponin and peptide levels decreased in the mavacamten arm and increased in the placebo arm.

Two patients in each group experienced adverse events: two episodes of syncope and an inappropriate shock delivered by an ICD in the treatment group and in the placebo group chest pain and suicidal ideation. No patient had an LVEF reduction to <50%, and no deaths occurred during the trial.

“These results are very encouraging. Patients feel better, and their hearts look better,” said Rossano. “Beyond symptom relief, there’s a signal that this may be favorably remodeling the heart, which could improve the natural history of the disease.” The authors say this suggests that it “could be important to start children on this therapy when they’re young, before they’ve had many decades of ongoing injury to the heart from the obstruction.”

Study limitations included its relatively small size, short duration and predominantly White population. Investigators plan to continue tracking outcomes for at least 50 weeks and study the drug’s efficacy in children younger than 12 years old and with different types of HCM.

Clinical Topics: Congenital Heart Disease and Pediatric Cardiology, Heart Failure and Cardiomyopathies

Keywords: ACC Annual Scientific Session, ACC26, New Orleans, Cardiomyopathy, Hypertrophic, Oxygen Consumption, Dyspnea, Troponin, Fatigue, Peptides, Adolescent