FDA Accepts Cytokinetics' NDA for Aficamten to Treat Obstructive Hypertrophic Cardiomyopathy

Cytokinetics, Incorporated (Nasdaq: CYTK) announced on December 2, 2024, that the U.S. Food & Drug Administration (FDA) has accepted the company's New Drug Application (NDA) for aficamten. This new cardiac myosin inhibitor is designed for the treatment of obstructive hypertrophic cardiomyopathy (HCM).

The NDA has been assigned a standard review with a target action date of September 26, 2025, under the Prescription Drug User Fee Act (PDUFA). Notably, the FDA does not intend to hold an advisory committee meeting regarding this application.

Robert I. Blum, President and CEO of Cytokinetics, emphasized the significance of the NDA acceptance, stating that it marks a crucial milestone for the company. He noted that if the FDA approves aficamten, it could become a preferred treatment option for obstructive HCM due to its benefits in improving exercise capacity, clinical outcomes, and symptom burden, as demonstrated in the pivotal Phase 3 clinical trial, SEQUOIA-HCM. He also highlighted the consistent positive effects across all subgroups and the favorable safety profile of aficamten.

The NDA submission is supported by the SEQUOIA-HCM trial results, which were published in the New England Journal of Medicine. The trial showed that aficamten significantly improved exercise capacity over 24 weeks compared to a placebo. Specifically, patients treated with aficamten saw an increase in peak oxygen uptake (pVO2) by 1.8 ml/kg/min measured through cardiopulmonary exercise testing (CPET), contrasting with no change in the placebo group. Significant improvements were also observed in various secondary endpoints, including the Valsalva left ventricular outflow tract (LVOT) gradient and New York Heart Association (NYHA) Functional Class. Notably, no severe side effects such as worsening heart failure or low ejection fraction were reported.

Additional analyses indicated that aficamten treatment led to favorable cardiac remodeling and improvements in cardiac structure and function without compromising systolic function.

In January 2021, the FDA granted aficamten Orphan Drug Designation for treating symptomatic HCM and Breakthrough Therapy Designation for obstructive HCM in December 2021. Aficamten is a selective, small molecule inhibitor of cardiac myosin, developed to reduce myocardial hypercontractility associated with HCM by binding at a specific allosteric site on cardiac myosin.

The comprehensive development program for aficamten aims to assess its efficacy in enhancing exercise capacity and alleviating symptoms in HCM patients, along with its long-term impact on cardiac structure and function. Current clinical evaluations include MAPLE-HCM, comparing aficamten as monotherapy to metoprolol; ACACIA-HCM, for non-obstructive HCM; CEDAR-HCM, for pediatric patients with obstructive HCM; and FOREST-HCM, an open-label extension study.

Hypertrophic cardiomyopathy (HCM) is characterized by an abnormal thickening of the heart muscle, leading to a smaller and stiffer left ventricle, which affects the heart's ability to pump blood effectively. This results in reduced exercise capacity and various symptoms such as chest pain, dizziness, and shortness of breath. HCM is a common inherited cardiovascular disorder, with a significant portion of patients remaining undiagnosed. Those with HCM are at increased risk of severe cardiovascular conditions, including atrial fibrillation, stroke, and sudden cardiac death.

Cytokinetics is dedicated to developing therapies for diseases affecting cardiac muscle performance. With the advancement of aficamten, the company is making strides in its regulatory submissions across the U.S., Europe, and China. Additionally, Cytokinetics is involved in the development of other therapeutic candidates such as omecamtiv mecarbil for heart failure and CK-586 for heart failure with preserved ejection fraction (HFpEF).

The company's efforts reflect its commitment to improving the lives of patients suffering from debilitating heart conditions through innovative muscle biology-directed therapies.