ODYSSEY-HCM trial (mavacamten in symptomatic nonobstructive hypertrophic cardiomyopathy)

Hypertrophic cardiomyopathy (HCM) is a myocardial disease characterized by increase left ventricular (LV) wall thickness not solely explained by abnormal loading conditions.1 According to the presence of LV outflow tract obstruction (LVOTO), HCM can be classified as obstructive or non-obstructive.1 In patients with obstructive HCM, mavacamten—a selective, allosteric, reversible, small-molecule cardiac myosin inhibitor—has been shown to reduce myosin ATPase activity, as well as the increased contractile force and calcium sensitivity induced by sarcomeric variants.2 In clinical trials enrolling patients with obstructive HCM, mavacamten reduced LVOTO, and improved exercise capacity, symptoms and patient-reported health status compared with placebo.3 Based on the rationale that mavacamten targets the core molecular defect of HCM, it has been hypothesized that the drug might also provide beneficial effects in non-obstructive HCM. In a multicentre, double-blind, placebo-controlled phase II trial, treatment with mavacamten was significantly associated with improvements in biomarkers [i.e. reduction from baseline to week 16 in N-terminal pro-B-type natriuretic peptide (NT-proBNP) and troponin I], compared with placebo.4 The preliminary findings supported the development of a phase III trial to further evaluate the potential role of mavacamten in patients with non-obstructive HCM.