Overview

• In the phase 3 MAPLE-HCM trial, aficamten improved peak oxygen uptake versus metoprolol at 24 weeks (1.1 vs −1.2 mL/kg/min; between-group difference 2.3; P < .001).
• Aficamten also outperformed on key secondary measures, including NYHA class improvement, KCCQ score, NT-proBNP reduction, and lower left ventricular outflow tract gradients, with benefits consistent across prespecified subgroups.
• Short-term safety was comparable between groups, with serious adverse events in 8% on aficamten and 7% on metoprolol and minimal overall effect on left ventricular ejection fraction.
• In the ODYSSEY-HCM study of nonobstructive disease, mavacamten showed trends but failed to reach statistical significance for both primary endpoints at 48 weeks, and treatment interruptions were more frequent than with placebo.
• Aficamten remains under FDA review with a decision expected by the end of 2025, experts see potential for guideline reassessment pending approval and longer-term data, and MAPLE-HCM was funded by Cytokinetics.