The following is a summary of “Phase 2 Study of Aficamten in Patients With Obstructive Hypertrophic Cardiomyopathy,” published in the Januray 2023 issue of Cardiology by Maron, et al.

In obstructive hypertrophic cardiomyopathy (oHCM), blockage of the left ventricular outflow tract (LVOT) 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. Therefore, Aficamten’s safety and effectiveness in treating patients with oHCM were assessed by researchers for a study.

In two dose-finding cohorts, patients with oHCM with LVOT gradients of ≥30 mm Hg at rest or ≥50 mm Hg with Valsalva were randomized 2:1 to receive aficamten (n = 28) or a placebo (n = 13). Doses were adjusted based on gradients and the ejection fraction (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.

Aficamten decreased gradients from baseline to 10 weeks with Valsalva maneuvers (−36 ± 27 mm Hg and −53 ± 44 mm Hg, P = 0.001 and <0.0001 vs. placebo, respectively) and at rest  (mean difference: −40 ± 27 mm Hg, and −43 ± 37 mm Hg in Cohorts 1 and 2, P = 0.0003 and P = 0.0004 vs. placebo, respectively). EF was somewhat decreased (−6% ± 7.5% and −12% ± 5.9%, P = 0.007 and P < 0.0001 vs. placebo, respectively). Cohorts 1 and 2 both had symptomatic improvement in ≥1 New York Heart Association functional class: 31% on placebo, 43% & 64% on aficamten, respectively (nonsignificant). N-terminal pro-B-type natriuretic peptide was decreased with aficamten (62% less than with placebo, P = 0.0002). There were no treatment halts, and side effects were comparable across treatment arms.

Aficamten significantly decreased LVOT gradients, and most patients had improvements in their biomarkers and symptoms. The findings demonstrated the therapeutic potential of sarcomere-targeted therapy in managing oHCM.

Reference: jacc.org/doi/10.1016/j.jacc.2022.10.020