Aficamten improves outcomes of obstructive hypertrophic cardiomyopathy

A new study by Martin Maron and team showed that aficamten significantly decreased left ventricular outflow tract (LVOT) gradients, and the majority of patients had improvements in their biomarkers and symptoms. The findings of this study were published in the Journal of the American College of Cardiology.

In obstructive hypertrophic cardiomyopathy (oHCM), blockage of the left ventricular outflow system plays a significant role in the development of heart failure symptoms. The next-generation cardiac myosin inhibitor aficamten may reduce gradients and lessen symptoms in these individuals. 

In two dose-finding cohorts, oHCM patients with LVOT gradients of less than ≥30 mm Hg at rest or more than ≥50 mm Hg with Valsalva were randomized 2:1 to receive aficamten (n = 28) or a placebo (n = 13). Based on gradients and the ejection fraction, doses were adjusted (EF). Over a 10-week treatment period and following a 2-week washout, safety and changes in gradient, EF, New York Heart Association functional class, and cardiac biomarkers were evaluated.

The key findings of this study were:

1. Aficamten decreased gradients from baseline to 10 weeks with Valsalva maneuvers (mean difference: −36 ± 27 mm Hg and −53 ± 44 mm Hg, P = 0.001 and 0.0001 versus placebo, respectively) and at rest (mean difference: −40 ± 27 mm Hg and −43 ± 37 mm Hg in Cohorts 1 and 2, respectively).

2. EF was somewhat decreased −6% ± 7.5% and −12% ± 5.9%, P = 0.007 and P 0.0001, respectively, versus placebo.

3. 31% of those taking the placebo saw symptomatic improvement in the first New York Heart Association functional class, compared to 43% and 64% of those on the medication aficamten in Cohorts 1 and 2, respectively (nonsignificant).

4. N-terminal pro-B-type natriuretic peptide was decreased by aficamten. There were no treatment halts, and side effects were comparable across treatment arms.

Reference:

Maron, M. S., Masri, A., Choudhury, L., Olivotto, I., Saberi, S., Wang, A., Garcia-Pavia, P., Lakdawala, N. K., Nagueh, S. F., Rader, F., Tower-Rader, A., Turer, A. T., Coats, C., Fifer, M. A., Owens, A., Solomon, S. D., Watkins, H., Barriales-Villa, R., Kramer, C. M., … Abraham, T. (2023). Phase 2 Study of Aficamten in Patients With Obstructive Hypertrophic Cardiomyopathy. In Journal of the American College of Cardiology (Vol. 81, Issue 1, pp. 34–45). Elsevier BV. https://doi.org/10.1016/j.jacc.2022.10.020