AFICAMTEN was found to be a safe and effective treatment for symptomatic nonobstructive hypertrophic cardiomyopathy (nHCM), showing significant improvements in symptoms, cardiac biomarkers, and quality of life measures.
The REDWOOD-HCM Cohort 4 trial was an open-label phase 2 study evaluating aficamten in 41 patients with nHCM across 15 centres in North America and Europe. Participants had preserved left ventricular ejection fraction (LVEF ≥ 60%), elevated NT-proBNP (>300 pg/mL), and moderate-to-severe symptoms. They received aficamten at doses of 5–15 mg daily over 10 weeks, adjusted based on LVEF. At the end of the treatment period, 55% of patients experienced an improvement of at least one New York Heart Association (NYHA) functional class, with 29% becoming asymptomatic. Improvements in the Kansas City Cardiomyopathy Questionnaire score were seen in 55% of patients, with reductions in NT-proBNP by 56% (p < 0.001) and cardiac troponin I by 22% (p < 0.005). A modest reduction in mean LVEF (−5.4% ± 10%) was observed, though values remained within normal ranges. Three patients experienced asymptomatic LVEF reductions below 50%, which resolved after a two-week washout period. One fatal arrhythmic event occurred in a patient with a history of severe cardiac risk, deemed unrelated to the treatment.
These findings suggest that aficamten offers a promising new option for managing symptoms and improving clinical status in nHCM, where treatment options have been limited to off-label use of heart failure therapies. The drug’s favourable safety and tolerability profile supports further evaluation in the upcoming phase 3 ACACIA-HCM trial. Future research should focus on refining the dosing strategy and exploring the long-term impact of aficamten on functional capacity, quality of life, and disease progression. For clinical practice, aficamten represents a step forward in addressing the unmet needs of patients with nHCM, offering hope for tailored management that targets the disease’s underlying mechanisms.
Katrina Thornber, EMJ
Reference
Masri A et al. Efficacy and Safety of Aficamten in Symptomatic Nonobstructive Hypertrophic Cardiomyopathy: Results From the REDWOOD-HCM Trial, Cohort 4. Journal of Cardiac Failure. 2024;30(11)1439-48.
