Cytokinetics Drug Bests Standard Care in Heart Study
Aficamten proves superior to metoprolol for hypertrophic cardiomyopathy, positioning the drug for a potential shift in treatment standards.
Cytokinetics, Inc. (CYTK) has unveiled pivotal Phase 3 clinical trial results showing its investigational heart drug, aficamten, is superior to the long-standing standard-of-care treatment, metoprolol. The findings, presented at the European Society of Cardiology Congress and simultaneously published in The New England Journal of Medicine, could potentially upend a six-decade reliance on beta-blockers for patients with obstructive hypertrophic cardiomyopathy (oHCM).
The study, dubbed MAPLE-HCM, met its primary endpoint by demonstrating a significant improvement in exercise capacity for patients treated with aficamten. After 24 weeks, patients on aficamten saw their peak oxygen uptake (pVO2) increase by an average of 1.1 mL/kg/min. In stark contrast, those receiving metoprolol experienced a decrease of 1.2 mL/kg/min, marking a statistically significant difference of 2.3 mL/kg/min between the two groups.
Hypertrophic cardiomyopathy is a genetic condition where the heart muscle thickens, making it harder to pump blood, and can lead to shortness of breath, chest pain, and in severe cases, sudden cardiac death. For over 60 years, beta-blockers have been the first-line therapy.
“These results call into question the reliance on beta-blockers as the initial treatment modality for obstructive HCM that has prevailed for over 60 years,” said Dr. Pablo Garcia-Pavia, the trial's lead investigator from Hospital Universitario Puerta de Hierro in Madrid. He added that the trial provides “strong ground in order to change the algorithm of therapies that we use for this disease.”
The positive data extended beyond the primary goal. Aficamten also proved superior in five of six secondary endpoints, including significant improvements in patient symptoms, functional capacity, and reductions in the physical obstruction of blood flow from the heart. Notably, 51% of patients on aficamten improved by at least one New York Heart Association (NYHA) functional class, compared to just 26% of those on metoprolol.
While both drugs had similar overall rates of adverse events, aficamten appeared more tolerable. Nearly 30% of patients on metoprolol required a dose reduction due to side effects like low blood pressure or dizziness, compared to only 4.5% of patients in the aficamten arm.
Analysts have a ‘Moderate Buy’ consensus on Cytokinetics, with price targets suggesting a potential upside of over 85% from its recent price of around $35 per share. While the company's stock has underperformed over the past year, the successful trial data is a critical catalyst. The market has reacted with high expectations as the company heads toward a key regulatory milestone.
The U.S. Food and Drug Administration (FDA) has granted aficamten Breakthrough Therapy Designation and is expected to make an approval decision by its Prescription Drug User Fee Act (PDUFA) date of December 26, 2025. With approximately $1.0 billion in cash, Cytokinetics is well-capitalized to support the potential commercial launch of what could become a new standard in cardiac care.