Aficamten Demonstrates Superior Efficacy to Metoprolol in Treating Symptomatic Obstructive Hypertrophic Cardiomyopathy

A recent Phase III clinical trial has shown that aficamten, a novel cardiac myosin inhibitor, outperforms the traditional beta-blocker metoprolol in improving symptoms and exercise capacity in patients with obstructive hypertrophic cardiomyopathy (HCM). The study was presented at ESC Congress 2025 and published in the New England Journal of Medicine.

Obstructive HCM is a condition characterized by abnormal thickening of the heart muscle, which impairs heart function and causes symptoms like shortness of breath, chest pain, and fatigue. While beta-blockers such as metoprolol are commonly used to manage these symptoms, their effects are limited as they do not target the underlying disease mechanisms.

The MAPLE-HCM trial was a global, randomized, double-blind, double-dummy study involving 71 sites across multiple countries, including North America, Europe, Israel, and China. Researchers enrolled adults with symptomatic obstructive HCM who had NYHA functional class II or III symptoms, reduced functional capacity, and other clinical markers of disease severity. Participants were assigned to receive either aficamten (dosed between 5 to 20 mg) or metoprolol (dosed between 50 to 200 mg), with dose titrations as tolerated.

Key findings from the trial demonstrated that after 24 weeks of treatment, patients on aficamten had a significant increase in peak oxygen uptake, averaging 1.1 mL/kg/min, whereas those on metoprolol experienced a decline of 1.2 mL/kg/min. This resulted in a notable difference of 2.3 mL/kg/min favoring aficamten. Improvements were consistent across various patient subgroups, including newly diagnosed and treatment-naive cases.

Beyond exercise capacity, aficamten also improved symptoms and health status. Over half of the patients treated with aficamten experienced at least one class improvement in NYHA functional class compared to about a quarter in the metoprolol group. Additionally, there were substantial gains in the Kansas City Cardiomyopathy Questionnaire score, indicating better quality of life.

Patients on aficamten showed improved heart hemodynamics, with reductions in left ventricular outflow tract gradient, left atrial volume index, and NT-proBNP levels, a biomarker linked to adverse outcomes. Safety profiles indicated that around 74% of both groups reported adverse events, with serious adverse events being relatively rare.

Overall, Dr. Pablo Garcia-Pavia highlighted that the trial's results suggest aficamten could be an effective monotherapy or first-line treatment option for symptomatic obstructive HCM, providing both symptomatic relief and functional benefits. These findings mark a significant step forward in targeted therapies for this condition.

Source: https://medicalxpress.com/news/2025-09-clinical-trial-aficamten-superior-metoprolol.html