Cytokinetics Announces EMA Validation for Aficamten in Obstructive Hypertrophic Cardiomyopathy Treatment

SOUTH SAN FRANCISCO, Calif., Dec. 23, 2024, Cytokinetics, Incorporated (Nasdaq: CYTK) has announced that the European Medicines Agency (EMA) has accepted the Marketing Authorization Application (MAA) for aficamten, a pioneering cardiac myosin inhibitor, aimed at treating obstructive hypertrophic cardiomyopathy (HCM). The application will now proceed to evaluation by the Committee for Medicinal Products for Human Use (CHMP).

Robert I. Blum, President and CEO of Cytokinetics, expressed the significance of this milestone, noting that with regulatory submissions already in progress in the United States and China, the MAA validation is crucial for potentially expanding treatment access to more patients globally. The company is eager to collaborate with the EMA throughout this review process.

The foundation of the MAA lies in data from the SEQUOIA-HCM trial, a crucial Phase 3 study that assessed the effects of aficamten in patients with symptomatic obstructive HCM. These findings were published in the New England Journal of Medicine. The U.S. Food and Drug Administration (FDA) had previously accepted the New Drug Application (NDA) for aficamten, assigning a review deadline of September 26, 2025.

SEQUOIA-HCM was a pivotal trial focusing on the safety and efficacy of aficamten for those suffering from symptomatic obstructive HCM. The results indicated that a 24-week treatment course with aficamten significantly enhanced exercise capacity compared to a placebo. Specifically, participants experienced an increase in peak oxygen uptake (pVO2) by 1.8 ml/kg/min when measured through cardiopulmonary exercise testing (CPET), compared to no change in the placebo group. This improvement was statistically significant across all ten secondary endpoints, which included metrics such as the Valsalva left ventricular outflow tract (LVOT) gradient, New York Heart Association (NYHA) Functional Class, and the Kansas City Cardiomyopathy Clinical Summary Score (KCCQ-CSS). Moreover, the study observed reduced incidents of treatment-emergent serious adverse events in aficamten participants compared to those receiving a placebo. Importantly, aficamten did not lead to worsening heart failure or treatment interruptions due to decreased left ventricular ejection fraction (LVEF).

Aficamten works as a selective, small molecule inhibitor targeting cardiac myosin, developed from a comprehensive chemical optimization program. It aims to reduce myocardial hypercontractility by diminishing active actin-myosin cross-bridges in each cardiac cycle. In preclinical models, aficamten demonstrated the ability to bind directly to cardiac myosin at a specific allosteric site, effectively decreasing myocardial contractility without affecting systolic function.

The broader development program for aficamten seeks to determine its efficacy in improving exercise capacity and alleviating symptoms in individuals with HCM, alongside its potential long-term impact on cardiac structure and function. Presently, aficamten is under evaluation in various clinical trials, including MAPLE-HCM, ACACIA-HCM, CEDAR-HCM, and FOREST-HCM, targeting different patient populations and trial designs.

Hypertrophic cardiomyopathy (HCM) involves the abnormal thickening of the heart muscle, primarily affecting the left ventricle's ability to fill with blood properly, thus impeding cardiac function. This condition, the most prevalent monogenic inherited cardiovascular disorder, affects a substantial portion of the population, with two-thirds experiencing obstructive HCM. Those with HCM face elevated risks of cardiovascular complications and sudden cardiac death, particularly among younger individuals and athletes.

Cytokinetics is at the forefront of developing muscle biology-directed pharmaceuticals to address diseases that compromise heart muscle performance. The company is advancing the potential commercialization of aficamten and is also involved in the development of other drug candidates like omecamtiv mecarbil and CK-586, targeting various aspects of heart function and muscle performance.