Aficamten significantly superior to metoprolol in treatment of obstructive hypertrophic cardiomyopathy

Recently, the biopharmaceutical company Cytokinetics announced that its new drug Aficamten has achieved an important breakthrough in the pivotal Phase III clinical trial MAPLE-HCM for the treatment of obstructive hypertrophic cardiomyopathy (HCM). The trial successfully achieved its primary endpoint. The data showed that compared with the standard beta blocker metoprolol, Aficamten significantly increased the patient's peak oxygen uptake (pVO2), showing better efficacy.

The MAPLE-HCM trial is a randomized, double-blind, active-controlled clinical study with registration number NCT05767346 and enrolled a total of 175 patients with symptomatic hypertrophic cardiomyopathy and left ventricular outflow tract obstruction. The cardiac function of the enrolled patients was in the New York Heart Association (NYHA) classification from II to III, and Clinical manifestations were measured by the Kansas City Cardiomyopathy Questionnaire (KCCQ) score ranging from 35 to 90 points. At screening, the patient's resting left ventricular outflow tract gradient (LVOT-G) reaches or exceeds 30 mm Hg, or post-Valsalva maneuver LVOT-G exceeds 5 0mmHg, while the left ventricular ejection fraction remains above 60%, the respiratory exchange rate reaches 1.05 and above, and the peak oxygen uptake is lower than the predicted value of 100%.

In the trial design, patients were randomly assigned in a 1:1 ratio to receive Aficamten or metoprolol, with the primary focus being change in peak oxygen uptake (pVO2) from baseline to week 24 as measured by cardiorespiratory exercise testing. The results showed that the Aficamten group was significantly better than the metoprolol group in improving exercise capacity, proving the significant advantages of this drug in improving patients' cardiopulmonary function. At the same time, the safety analysis also showed that Aficamten was well tolerated and there were no obvious adverse events.

CytokineticsExecutive Vice President of Research and DevelopmentFady I. Dr. Maliksaid:“ThisMAPLE-HCM trial results prove for the first timeAficamtenprovides clinically significant treatment improvements as a single agent in patients with obstructive hypertrophic cardiomyopathy provides strong evidence for the potential benefit of Aficamten over existing treatment options. ” The company also revealed that complete data from the trial will be made public at an upcoming international medical conference, where more details will be disclosed.

AboutAficamten, an innovative cardiac myosin inhibitor. Its mechanism of action reduces the excessive contraction of the heart in patients with hypertrophic cardiomyopathy by limiting the number of active actin-myosin cross-bridges in cardiomyocytes, thereby alleviating the disease and improving cardiac function. Currently, the U.S. Food and Drug Administration (FDA) is reviewing a new drug application for Aficamten for the treatment of obstructive hypertrophic cardiomyopathy. The final regulatory decision is expected to be made before December 26, 2025. At the same time, the drug is also undergoing regulatory approval in Europe and China and is expected to provide new treatment options for patients around the world in the future.

Overall, the success of the Phase III trial of MAPLE-HCM not only paves the way for the clinical application of Aficamten, but also brings new hope for the treatment of obstructive hypertrophic cardiomyopathy. As the approval process progresses, Aficamten is expected to become the first innovative cardiac myosin inhibitor targeting this disease, helping to improve patients' quality of life and heart health.

References:Cytokinetics announces positive topline results from MAPLE-HCM. News release. Cytokinetics. May 13, 2025.