Mavacamten - A new disease-specific option for pharmacological treatment of symptomatic patients with hypertrophic cardiomyopathy

Current pharmacotherapy for hypertrophic cardiomyopathy (HCM) is not disease-specific and has suboptimal efficacy, often necessitating interventional treatment. EXPLORER-HCM was a phase 3, randomized, double-blind, placebo-controlled, multicenter clinical trial investigating the effects of mavacamten, a first-in-class selective cardiac myosin inhibitor, in patients with HCM, left ventricular outflow tract obstruction (LVOTO) and New York Heart Association (NYHA) class II or III symptoms. The primary endpoint was defined as either a ≥1.5 ml/kg/min increase in peak oxygen consumption (pVO2) and ≥1 NYHA class reduction or a ≥3.0 ml/kg/min pVO2 increase without NYHA class worsening. Secondary endpoints evaluated changes in post-exercise LVOT gradient, pVO2, NYHA class, Kansas City Cardiomyopathy Questionnaire-Clinical Summary Score (KCCQ-CSS), and Hypertrophic Cardiomyopathy Symptom Questionnaire Shortness-of-Breath subscore (HCMSQ-SoB). A total of 251 patients were randomized to receiving mavacamten or placebo. In conclusion, disease-specific treatment with mavacamten in patients with obstructive HCM led to reduced LVOTO and improvement in both objective functional parameters and patient-related health status.