FDA Sets Goal Date for Cardiomyopathy Drug, Aficamten

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Cytokinetics Inc. announced the FDA acceptance of new drug application for aficamten, for the treatment of obstructive hypertrophic cardiomyopathy (HCM), according to the details of a recent press release. A Prescription Drug User Fee Act (PDUFA) date has been set for Sept. 26, 2025. The FDA has no plans to hold an advisory committee meeting for this application.

Hypertrophic cardiomyopathy is a disease characterized by the abnormal thickening of the cardiac muscle, which is the middle layer of the heart. This results in symptoms such as chest pain, dizziness, shortness of breath or fainting during physical activity. It is the most common monogenetic inherited cardiac disorder with approximately 280,000 patients diagnosed and another 400,000 to 800,000 patients undiagnosed in the United States. Two-thirds of HCM patients have obstructive HCM which causes the muscles in the left ventricle to stiffen, leading to obstructed blood flow. The other third of patients have non-obstructive HCM.

Aficamten is an investigational small molecule cardiac myosin inhibitor. Preclinical models show that it reduces contraction of the heart muscle by binding directly to cardiac myosin, a protein that is considered a “molecular motor” because its plays a role in the regulation of contractions.

The NDA is based on the results of SEQUOIA-HCM, a phase 3 trial published in the New England Journal of Medicine in May 2024. Findings were also presented the American Heart Association Scientific Sessions in September 2024. A total of 282 patients were enrolled, with 142 patients who received aficamten and 140 patients who received placebo. Effectiveness was measured using cardiopulmonary exercise testing, according to the data.

Results showed that treatment with aficamten for 24 weeks resulted in peak oxygen uptake of 1.8 ml per kilogram per minute compared with 0.0 ml kilogram per minute in patients treated with placebo. Improvements were also seen in all 10 prespecified secondary endpoints. Treatment emergent serious adverse events occurred in 5.6% and 9.3% of patients on aficamten and placebo, respectively, but there were no reports of worsening heart failure. There were no instances of worsening heart failure or treatment interruptions due to low left ventricular ejection fraction, a measure of how much blood the left ventricle pumps out with each contraction.

“The results from SEQUOIA-HCM, the pivotal phase 3 clinical trial, which form the foundation of the NDA, demonstrated that aficamten has a positive impact on exercise capacity, clinical outcomes, symptom burden and cardiac biomarkers in patients with HCM, with a consistent effect across all prespecified subgroups and a favorable safety and tolerability profile,” Robert I. Blum, president and CEO of Cytokinetics said in the news release.

Aficamten is also being evaluated in the following ongoing trials examining the drug:

• MAPLE-HCM - as a monotherapy compared with metoprolol as monotherapy
• ACACIA-HCM – effectiveness in patients with non-obstructive HCM
• CEDAR-HCM – effectiveness in the pediatric population
• FOREST-HCM – in open label extension study

Aficamten was previously granted orphan drug designation and breakthrough therapy designation for HCM in January 2021 and December 2021, respectively.