Aficamten for Symptomatic Nonobstructive Hypertrophic Cardiomyopathy.

August 28, 2026| Source: The New England journal of medicine

Nonobstructive hypertrophic cardiomyopathy (HCM) is a common condition that is associated with substantial morbidity and no proven medical therapy. Whether treatment with aficamten, a cardiac myosin inhibitor, can benefit patients with this condition is unknown. In this phase 3, multinational, double-blind trial, we randomly assigned adults with symptomatic nonobstructive HCM in a 1:1 ratio to receive aficamten (starting dose, 5 mg; maximum dose, 20 mg) or placebo for up to 72 weeks. The dual primary end points were the change from baseline to week 36 in peak oxygen uptake and in the Kansas City Cardiomyopathy Questionnaire clinical summary score (KCCQ-CSS; range, 0 to 100, with higher scores indicating better health status). A total of 258 patients were assigned to receive aficamten and 259 to receive placebo. The mean age of the patients was 55.1 years, and 53.6% were women. At 36 weeks, the change in the KCCQ-CSS was 11.4 points (95% confidence interval [CI], 9.6 to 13.2) in the aficamten group and 8.4 points (95% CI, 6.6 to 10.2) in the placebo group (least-squares mean difference, 3.0 points; 95% CI, 0.5 to 5.5; P = 0.02). The mean change in the peak oxygen uptake at week 36 was 0.64 ml per kilogram of body weight per minute (95% CI, 0.32 to 0.95) in the aficamten group and -0.03 ml per kilogram per minute (95% CI, -0.35 to 0.28) in the placebo group (least-squares mean difference, 0.67 ml per kilogram per minute; 95% CI, 0.22 to 1.11; P = 0.003). Reversible reductions in left ventricular ejection fraction to less than 50% occurred in 27 patients (10.5%) receiving aficamten and in 2 patients (0.8%) receiving placebo. Serious adverse events occurred in 52 patients (20.2%) and 38 patients (14.7%), respectively. Among patients with symptomatic nonobstructive HCM, treatment with aficamten resulted in a significantly greater change in exercise capacity and patient-reported health status than placebo at 36 weeks. (Funded by Cytokinetics; ACACIA-HCM ClinicalTrials.gov number, NCT06081894.).

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