Cytokinetics Shows Aficamten Outperforms Metoprolol and Sustains Safety through 96 Weeks
CYTK•Cytokinetics presented Phase 3 MAPLE-HCM data showing aficamten improved exercise capacity, outflow gradients and reduced NT-proBNP at all doses versus metoprolol. In the FOREST-HCM extension, 96-week treatment maintained stable arrhythmia rates and delivered durable LVOT gradient reductions of –40.3 mmHg and –45.6 mmHg.
1. Phase 3 MAPLE-HCM Efficacy
The MAPLE-HCM trial compared aficamten to metoprolol in symptomatic obstructive HCM, demonstrating dose-dependent improvements in peak oxygen consumption, left ventricular outflow tract gradients and NT-proBNP levels at all tested doses. A secondary sex-based analysis showed women (42% of participants) achieved identical +2.2 mL/kg/min pVO2 gains and similar KCCQ-CSS increases despite more severe baseline disease.
2. FOREST-HCM Long-Term Safety and Durability
In the open-label FOREST-HCM extension, 122 patients treated up to 96 weeks exhibited no increase in non-sustained ventricular tachycardia or atrial fibrillation compared with baseline, including those who discontinued beta blockers. A separate 48-week Chinese cohort showed no serious adverse events or LVEF <50%, with resting LVOT gradients falling by –40.3 mmHg and Valsalva gradients by –45.6 mmHg (both p<0.001).
3. SEQUOIA-HCM Left Atrial Remodeling
The SEQUOIA-HCM analysis assessed aficamten’s impact on left atrial mechanics in 269 patients, revealing significant improvements in LA reservoir strain (+2.9%; p=0.004) and conduit strain (+2.2%; p=0.001), alongside a –3.5 mL/m² reduction in LA volume index versus placebo. These changes correlated with enhanced exercise capacity, indicating favorable atrial remodeling effects.
