Cytokinetics Announces Primary Phase 3 Data for Aficamten in Hypertrophic Cardiomyopathy.

Cytokinetics has announced primary results from its Phase 3 MAPLE-HCM trial for lead asset aficamten in symptomatic obstructive hypertrophic cardiomyopathy. The trial aimed to evaluate the efficacy and safety of aficamten in patients with this condition.

Cytokinetics, Incorporated has announced positive results from its Phase 3 MAPLE-HCM trial, demonstrating that the investigational drug aficamten outperforms the standard beta-blocker metoprolol in improving exercise capacity for patients with obstructive hypertrophic cardiomyopathy (oHCM). The trial, presented at the European Society of Cardiology Congress 2025 in Madrid, involved 175 patients and showed significant improvements in peak oxygen uptake (pVO2) and other clinically relevant endpoints, suggesting that aficamten may challenge long-standing treatment practices relying on beta-blockers [1].

The primary endpoint of the MAPLE-HCM trial was change in peak oxygen uptake at week 24, with secondary endpoints including improvement in the New York Heart Association (NYHA) functional class and Kansas City Cardiomyopathy Questionnaire clinical summary score (KCCQ-CSS). At 24 weeks, peak oxygen uptake had changed by 1.1 ml per kilogram of body weight per minute (95% CI, 0.5 to 1.7) in the aficamten group and -1.2 ml per kilogram per minute (95% CI, -1.7 to -0.8) in the metoprolol group (least-squares mean between-group difference, 2.3 ml per kilogram per minute; 95% CI, 1.5 to 3.1; P .001). Patients receiving aficamten also had significantly greater improvements in NYHA class, KCCQ-CSS, left ventricular outflow tract gradient, NT-proBNP level, and left atrial volume index than patients given metoprolol [1].

The trial's lead investigator, Pablo Garcia-Pavia, MD, PhD, emphasized the potential of aficamten to change the algorithm of therapies for HCM. He noted that while beta-blockers have been the standard of care, the results of the MAPLE-HCM trial show that aficamten is superior to metoprolol, the most commonly used beta-blocker for this indication [1].

Despite these promising results, the trial had several limitations. Garcia-Pavia and colleagues noted the possibility for bias regarding investigator assumption of treatment assignment, given the negative chronotropic effect of metoprolol. Additionally, other nonvasodilating beta-blockers may have effects different from those of metoprolol, and the dose-adjustment protocol used for metoprolol may differ from strategies implemented in local practice [1].

The MAPLE-HCM trial confirmed the therapeutic safety and efficacy of aficamten in obstructive HCM, similar to the previous SEQUOIA-HCM trial. Amrut Ambardekar, MD, wrote in a related editorial for NEJM that the current data shows that myosin inhibition with either mavacamten or aficamten could be a suitable option for symptomatic obstructive HCM [2].

Aficamten is currently under regulatory review by the FDA, with a decision expected by December 26, 2025. Cytokinetics will host an investor event on September 2, 2025, to discuss these findings [2].

References:
[1] Garcia-Pavia P, Maron M, Masri A, et al. Aficamten or Metoprolol Monotherapy for Obstructive Hypertrophic Cardiomyopathy. NEJM. August 30, 2025. Accessed August 30, 2025. DOI: 10.1056/NEJMoa2504654
[2] Ambardekar A. Expanding the Role of Myosin Inhibition in Hypertrophic Cardiomyopathy – A Tale of Two Conditions. NEJM. August 30, 2025. Accessed August 30, 2025. DOI: 10.1056/NEJMe2512100