Efficacy And Safety Of Aficamten In Patients With Symptomatic Obstructive Hypertrophic Cardiomyopathy: Interim Results From The Randomized Evaluation Of Dosing With Ck-3773274 In Hypertrophic Cardiomyopathy Open Label Extension Study

Introduction Aficamten, a next-generation cardiac myosin inhibitor, decreases myocardial contractility by reducing myosin-actin interactions in obstructive hypertrophic cardiomyopathy (oHCM). In the Phase 2 REDWOOD-HCM (NCT04219826) study, patients in Cohorts 1 (dose range 5-15 mg) and 2 (dose range 10-30 mg) were randomized to receive treatment with aficamten or placebo for 10 weeks. Over this period, aficamten was well tolerated, reduced left ventricular outflow tract (LVOT) gradients, improved NYHA functional class, and reduced N-terminal brain natriuretic peptide (NT-proBNP) as compared with placebo. Thus far, 28 eligible patients from Cohorts 1 and 2 from the REDWOOD-HCM study have enrolled into REDWOOD-HCM OLE (NCT04848506), a planned 5-year open-label extension study. We will present interim results from the first 6 months of REDWOOD-HCM OLE. Hypothesis We hypothesized that 6 months of aficamten treatment would be well-tolerated in patients with oHCM. Methods Eligible patients with oHCM who completed the REDWOOD-HCM study were invited to participate in REDWOOD-HCM OLE. Aficamten was initiated at 5 mg daily in an open-label fashion and escalated based solely on echocardiographic parameters at 2-week intervals in 5 mg increments to a maximum of 15 mg (provided LV ejection fraction (LVEF) ≥50% and resting LVOT gradient ≥30 mmHg or Valsalva LVOT gradient ≥50 mmHg on site-read echocardiograms). Efficacy endpoints analyzed up to 24 weeks of treatment included resting and provoked LVOT gradients, NYHA class, Kansas City Cardiomyopathy Questionnaire, NT-proBNP and high-sensitivity cardiac troponin I (hs-cTnI). The primary outcome of safety endpoints included incidence of adverse events, serious adverse events, LVEF <50% (requires dose reduction), and LVEF ≤40% (requires temporary discontinuation and dose reduction). Results Baseline, Week 12, and Week 24 safety and efficacy data will be presented. Conclusions Aficamten has been shown to be safe and effective in lowering LVOT gradients in oHCM over a 10-week treatment period compared to placebo. The current study will provide an interim update on aficamten's safety and efficacy from the initial 6 months of the open-label extension study.