Aficamten Phase 3 Trial Shows Symptom and Exercise Gains in Non-Obstructive HCM

The ACACIA-HCM study randomized patients across 182 sites to aficamten or placebo with LVEF-guided titration. Dual primary endpoints captured symptom burden via Kansas City Cardiomyopathy Questionnaire Clinical Summary Score and maximal exercise capacity by cardiopulmonary exercise testing. Aficamten raised KCCQ-CSS by 11.4 points against 8.4 on placebo and increased peak VO2 by 0.64 mL/kg/min while placebo showed negligible change, with benefits emerging by week 12.

Prior myosin-inhibitor data from SEQUOIA-HCM addressed only obstructive disease; this trial extends the mechanism to the non-obstructive population where no approved disease-specific therapy exists. Reductions in NT-proBNP and NYHA class improvements align with reduced myocardial strain, yet the 10 % incidence of LVEF below 50 % underscores the need for ongoing echocardiographic monitoring beyond the 72-week protocol.

Contextual analysis reveals that placebo gains in KCCQ-CSS suggest substantial background care effects, narrowing the absolute treatment difference. Regulatory precedent from mavacamten indicates FDA may require longer-term safety data on systolic function before broad labeling.

Next steps include submission for regulatory review and planned extension studies tracking LVEF recovery after drug withdrawal and real-world adherence patterns.