Abstract 10201: Efficacy of Mavacamten in Patients with Symptomatic Hypertrophic Cardiomyopathy: Sub-Group Analyses by Background Beta-Blocker Use from the EXPLORER-HCM and MAVA-LTE Studies

Abstract

Introduction: Mavacamten, a selective inhibitor of cardiac myosin, improved symptoms and exercise capacity (pVO 2 ) in adults with obstructive hypertrophic cardiomyopathy (oHCM) (EXPLORER-HCM; NCT03470545). Improvements in pVO 2 were observed regardless of whether patients were receiving beta-blockers (BB), but were greater in those not receiving BB. To examine whether BB lessen the effect of mavacamten on other parameters such as function, echocardiographic parameters, biomarkers and symptoms further sub-group analyses of EXPLORER-HCM and the mavacamten long-term extension (MAVA-LTE; NCT03723655) studies were conducted. Methods: In the phase 3, placebo-controlled EXPLORER-HCM trial, randomization was stratified by BB usage, and pre-specified sub-group analyses were performed. MAVA-LTE is an ongoing study evaluating long-term mavacamten dosing in patients with HCM who completed EXPLORER-HCM or MAVERICK. Sub-group analyses by BB usage for the same endpoints, if available, were performed post hoc including only patients with oHCM. Results: Results are shown in the Table. In EXPLORER-HCM, the majority of patients not taking BB received non-dihydropyridine calcium channel blockers (mavacamten [25/29 patients] or placebo [17/33]); this trend continued in MAVA-LTE. In EXPLORER-HCM, the mean change from baseline in pVO 2 was lower in the sub-group using BB (1.1 ml/kg/min) vs not using BB (2.2 ml/kg/min), while the heart rate-independent parameter, VE/VCO 2 slope (ventilatory efficiency), improved similarly in both groups (-2.4 vs -2.7). Improvements in symptoms (NYHA Class, KCCQ-CSS), LVOT gradients, LAVI, and biomarkers (NT-proBNP and cTnI) were similar between subgroups across both studies. Conclusion: In EXPLORER-HCM, the reduced effect of mavacamten on pVO2 in BB users is likely due to the effect of BB on heart rate response during exercise. Mavacamten benefits were observed across a range of clinically meaningful parameters regardless of BB use.