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Aficamten: Enhancing Oxygen Utilization in Obstructive Hypertrophic Cardiomyopathy – Implications for Treatment Strategies and Everyday Functionality

Aficamten, an investigational drug for obstructive hypertrophic cardiomyopathy (HCM), has demonstrated promising results in a phase 3 trial by improving oxygen utilization during exercise. This breakthrough could offer a significant improvement in daily activities and overall quality of life for patients with obstructive HCM. The study, published in The New England Journal of Medicine, highlights the potential of aficamten to serve as a new therapeutic option alongside existing treatments like mavacamten and surgical interventions.

Key Points:

• Condition Overview
  • Hypertrophic cardiomyopathy (HCM) is the most common genetic heart disease, affecting about 1 in 500 individuals.
  • Obstructive HCM is more prevalent than non-obstructive HCM and involves thickened heart muscle obstructing blood flow from the left ventricle, increasing cardiac pressure.
• Symptoms and Risks
  • HCM symptoms can range from asymptomatic to chest pain, breathlessness, fatigue, dizziness, lightheadedness, syncope, arrhythmias, and edema.
  • It can lead to serious conditions like atrial fibrillation, heart failure, or sudden cardiac arrest.
• Current Treatments
  • Treatments for obstructive HCM include surgical removal of excess heart muscle and the use of mavacamten (Camzyos), which requires close monitoring due to interactions with other medications.
  • Mavacamten was approved by the FDA in 2022 for improving exercise capacity and symptoms in adults with symptomatic obstructive HCM.
• Aficamten Study
  • Aficamten is an oral selective cardiac myosin inhibitor that reduces excessive cardiac contraction, thereby lowering left ventricular outflow tract pressure.
  • The phase 3 trial included 282 adults (mean age 59.1 years; 59.2% men) with symptomatic obstructive HCM.
• Study Methodology
  • Participants received aficamten or placebo for 24 weeks, starting at 5 mg with a maximum dose of 20 mg, adjusted based on echocardiography results.
  • Primary endpoint: Change in peak oxygen uptake from baseline to week 24, measured via cardiopulmonary exercise testing.
  • Secondary endpoints: Changes in Kansas City Cardiomyopathy Questionnaire clinical summary score (KCCQ-CSS), NYHA functional class, pressure gradient post-Valsalva maneuver, eligibility duration for septal reduction therapy, and total workload at week 24.
• Study Results
  • Primary endpoint: Mean change in peak oxygen uptake was 1.8 mL/kg/min for aficamten vs 0.0 mL/kg/min for placebo (least-squares mean difference, 1.7 mL/kg/min; 95% CI, 1.0 to 2.4; P<0.001).
  • Secondary endpoints showed significant improvements with aficamten compared to placebo.
  • Adverse events incidence was similar between aficamten and placebo.
• Clinical Implications
  • Aficamten shows potential in improving exercise capacity and easing daily activities for patients with obstructive HCM.
  • This drug could serve as an additional therapeutic option, complementing current surgical and procedural treatments.

Hypertrophic cardiomyopathy is often inherited and is a common form of genetic heart disease. It can happen at any age, but most receive a diagnosis in middle age. It’s estimated that as many as 1 in every 500 young people in the United States have HCM, but a large percentage of people are undiagnosed.

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