The European Union has granted approval for Aficamten, a new medication targeting adults with symptomatic hypertrophic obstructive cardiomyopathy (HOCM). HOCM is the most common form of hypertrophic cardiomyopathy (HCM), a progressive heart condition characterized by thickening of the heart muscle and reduced capacity of the left ventricle. This results in impaired blood circulation and an increased risk of complications such as atrial fibrillation and stroke.

HOCM is often caused by mutations in the sarcomere proteins of the heart muscle. The disease leads to a narrowing of the left ventricular outflow tract (LVOT), obstructing the flow of blood from the heart. Patients typically experience symptoms such as shortness of breath, chest pain, and fatigue, significantly affecting their quality of life.

Innovative Mechanism of Action

Aficamten, like the previously approved drug Mavacamten, functions as a selective cardiac myosin inhibitor. These agents reduce the contractility of the heart muscle by inhibiting the formation of excessive myosin-actin cross-bridges, which are key contributors to hypercontractility, left ventricular hypertrophy, and reduced myocardial elasticity in HOCM. By targeting the underlying pathophysiology of the disease, Aficamten offers a disease-specific approach to therapy.

The approved use of Aficamten is for adults with symptomatic HOCM classified in the New York Heart Association (NYHA) functional classes II and III. This mirrors the indication already established for Mavacamten, providing an additional therapeutic option for affected patients.

Clinical Trial Results

The efficacy and safety of Aficamten were demonstrated in the randomized, double-blind, placebo-controlled phase III SEQUOIA-HCM trial. In this study, Aficamten showed a statistically significant improvement in the primary endpoint: the change in peak oxygen uptake (pVO2) from baseline to week 24 was greater in the Aficamten group compared to placebo. Additionally, the need for septal reduction therapy--a secondary endpoint--was lower among those receiving Aficamten.

Commonly reported side effects include dizziness, systolic dysfunction (defined as a left ventricular ejection fraction below 50 percent), palpitations, and increased blood pressure. The recommended starting dosage is 5 mg once daily, with a dose range of 5 to 20 mg per day. Unlike Mavacamten, Aficamten does not require CYP2C19 genotyping for dose determination, simplifying its use in clinical practice.

Ongoing Research

Beyond its current indication, Aficamten is also being evaluated in ongoing clinical trials. The ACACIA-HCM phase III study is investigating its effects in patients with non-obstructive HCM (nHCM), while the CEDAR-HCM trial is assessing its safety and efficacy in pediatric patients with HOCM. These studies aim to expand the potential therapeutic applications of Aficamten and provide evidence for its use in broader patient populations.

Implications for Patient Care

The EU approval of Aficamten represents a significant advancement in the management of HOCM, offering a targeted therapeutic option that addresses the underlying mechanisms of the disease. With its demonstrated ability to improve exercise capacity and reduce the need for invasive procedures, Aficamten may help improve outcomes and quality of life for patients with this chronic heart condition. Further research will clarify its role in other forms of hypertrophic cardiomyopathy and in pediatric populations.