Efficacy and Safety of Aficamten in Symptomatic Nonobstructive Hypertrophic Cardiomyopathy: Results From the REDWOOD-HCM Trial, Cohort 4

Background This open-label phase 2 trial evaluated the safety and efficacy of aficamten in patients with non-obstructive hypertrophic cardiomyopathy (nHCM). Methods Patients with symptomatic nHCM (left ventricular outflow tract obstruction gradient ≤30 mmHg, left ventricular ejection fraction LVEF ≥60%, N-terminal pro-B-type natriuretic peptide NT-proBNP >300 pg/mL) received aficamten 5–20 mg once daily (doses adjusted according to echocardiographic LVEF) for 10 weeks. Results 41 patients were enrolled (mean ± SD age 56 ± 16 years; 59% female). At Week 10, 22 (55%) patients experienced an improvement of ≥1 New York Heart Association class; 11 (29%) became asymptomatic. Clinically relevant improvements in Kansas City Cardiomyopathy Questionnaire Clinical Summary Scores occurred in 22 (55%) patients. Symptom relief was paralleled by reductions in NT-proBNP (56%; P < 0.001) and high-sensitivity cardiac troponin I (22%; P < 0.005). Modest reductions in LVEF (mean ± SD) of −5.4% ± 10 to 64.6% ± 9.1 were observed. Three (8%) patients had asymptomatic reduction in LVEF <50% (range: 41–48%), all returning to normal after 2 weeks of washout. One patient with prior history of aborted sudden cardiac death experienced a fatal arrhythmia during the study. Conclusions Aficamten administration for symptomatic nHCM was generally safe and associated with improvements in heart failure symptoms and cardiac biomarkers. TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT04219826 LAY SUMMARY Non-obstructive hypertrophic cardiomyopathy (nHCM) is a disease in which the heart muscle becomes abnormally thickened. There are no proven medical therapies. Aficamten is a new cardiac myosin inhibitor designed to target the underlying cause of HCM. REDWOOD-HCM Cohort 4 was the first study exploring the efficacy and safety of aficamten in people with symptoms from nHCM. Most patients reported improved health and functional status. There was also significant decrease in blood levels of biomarkers indicating excessive pressure within the heart and damage to heart muscle cells. These results support a larger placebo-controlled study of aficamten for people with nHCM (ACACIA-HCM).