Aficamten veilig en effectief bij langdurige behandeling van obstructieve HCM

BACKGROUND AND AIMS: Aficamten is a next-in-class, oral selective cardiac myosin inhibitor that ameliorates hypercontractility in hypertrophic cardiomyopathy (HCM). This study assessed the safety and efficacy of extended aficamten treatment in symptomatic obstructive HCM (oHCM). METHODS: Patients completing a parent aficamten study were eligible to enrol in FOREST-HCM (NCT04848506), an open-label study evaluating long-term aficamten treatment. RESULTS: Patients with oHCM (N = 296; mean age ±SD 61 ± 12.3 years, 44.3% female) enrolled between May 2021 and August 2024. Cumulative exposure was 352 patient-years; median follow-up 51.6 (IQR 41.5, 70.8) weeks. At Weeks 12 and 96, aficamten reduced Valsalva left ventricular outflow tract gradient by 56 ± 43 and 62 ± 33 mmHg from baseline (both P < 0.0001), with minimal reduction in left ventricular ejection fraction (LVEF) (-3% ± 6% and -5% ± 5%); 69% and 93% of participants had at least one NYHA class improvement; Kansas City Cardiomyopathy Questionnaire-Clinical Summary Score improved by 15 ± 16 and 16 ± 16 points. Treatment-emergent serious adverse events (TESAEs) occurred in 36 (12.2%) patients; no deaths, heart failure, or events considered related to aficamten were reported. One (0.3%) patient terminated therapy due to a TESAE (ischemic colitis). LVEF<50% occurred in 10 (3.4%) patients [exposure-adjusted incidence rate (EAIR): 2.9 per 100 patient-years] with 2 having non-serious mild/moderate dyspnoea. No treatment interruptions for LVEF<50%, and no events of LVEF<40% occurred. New-onset atrial fibrillation occurred in seven (2.4%) patients (EAIR 2.0 per 100 patient-years). CONCLUSIONS: Extended aficamten treatment in patients with symptomatic oHCM yielded early and sustained hemodynamic and clinical responses with low incidences of new-onset atrial fibrillation and LVEF<50%.