Mavacamten induces a clinical, hemodynamic, and biomarker response beyond the primary endpoint in EXPLORER-HCM: results from a post hoc machine learning analysis

Abstract Introduction Mavacamten, a first-in-class selective inhibitor of cardiac myosin, was demonstrated in EXPLORER-HCM (NCT03470545) to be superior placebo achieving primary endpoint either (1) ≥1.5 mL/kg/min increase peak oxygen consumption (pVO2) and at least one New York Heart Association (NYHA) class reduction, or (2) ≥3.0 pVO2 without NYHA worsening, adults with obstructive hypertrophic cardiomyopathy (oHCM). However, the observed benefits mavacamten were broader than endpoint, suggesting complex effect drug beyond improvements these two parameters. Purpose A post hoc investigation clinical effects EXPLORER-HCM. Methods EXPLORER data week 30 analyzed evaluate from baseline (specified above), secondary (e.g. postexercise left ventricular outflow tract gradient Kansas City Cardiomyopathy Questionnaire-Clinical Summary Score) exploratory endpoints circulating NT-ProBNP Troponin I). Responses classified as improved not based on published thresholds, standards analyses data. Patients grouped according their improvement status using unsupervised hierarchical clustering. Results The cluster analysis resulted four main groups following trends (Table); Group 1 = patients who met showed secondary/exploratory endpoints; 2 did meet endpoint; 3 substantial responses; 4 appreciable any endpoint. substantially larger proportion received compared (88% vs. 12%, respectively). similar trend exhibited (85% 15% placebo). consisted predominantly placebo-treated but had negligible responses (5% 95% clinically relevant this (10% 90% Conclusions Mavacamten associated accompanied by amelioration other measures oHCM pathophysiology. In contrast, most exhibit underlying These findings suggest potential underestimation impact prompt deeper examination efficacy endpoints. Funding Acknowledgement Type funding sources: Private company. Main source(s): MyoKardia, Inc., wholly owned subsidiary Bristol Myers Squibb