New drug for obstructive HCM outperforms the current standard of care
The first study in patients with symptomatic obstructive hypertrophic cardiomyopathy (HCM) to compare a cardiac myosin inhibitor to a beta blocker demonstrated superiority for the drug aficamten over the standard of care.
Cytokinetics announced positive results from the MAPLE-HCM (Metoprolol vs. Aficamten in Patients with LVOT Obstruction on Exercise Capacity in HCM) Phase 3 clinical trial comparing aficamten monotherapy to the beta blocker metoprolol. The company said MAPLE-HCM met its primary endpoint, demonstrating a statistically significant improvement in peak oxygen uptake (pVO2) from baseline to week 24. The safety and tolerability profile of aficamten were also favorable in comparison to metoprolol in this study.
"These results represent the first evidence that aficamten may be used as monotherapy to deliver clinically meaningful improvements in people living with obstructive hypertrophic cardiomyopathy,” Fady I. Malik, MD, PhD, Cytokinetics’ executive vice president of research and development, said in a statement. “Importantly, the results from MAPLE-HCM provide important context to the benefit of this potential new medicine compared to the current standard of care. We are grateful to the investigators, site personnel and patients who participated in MAPLE-HCM, and look forward to presenting the full results at an upcoming medical meeting.”
Aficamten is an investigational, selective, small-molecule cardiac myosin inhibitor. The company hopes the results of the study will help bring the drug to market as a next-in-class treatment for obstructive HCM. According to Cytokinetics, Aficamten was designed to "reduce the number of active actin-myosin cross bridges during each cardiac cycle and consequently suppress the myocardial hypercontractility that is associated with HCM."
MAPLE-HCM clinical trial design
MAPLE-HCM was a phase 3, multi-center, randomized, double-blind active-comparator clinical trial. The primary endpoint was the change in pVO2 from baseline to week 24 measured by cardiopulmonary exercise testing (CPET). Secondary endpoints included the change from baseline to week 24 in Kansas City Cardiomyopathy Questionnaire (KCCQ) score, the proportion of patients seeing at least one class improvement in New York Heart Association (NYHA) functional class, and changes in left ventricular mass index (LVMI), left atrial volume index (LAVI), post-Valsalva left ventricular outflow tract gradient (LVOT-G) and NT-proBNP.
The study included data from 175 patients randomized on a 1:1 basis to receive aficamten or metoprolol as monotherapy in a double-blind, double dummy fashion. Randomization was stratified by CPET exercise modality, treadmill or bicycle, and recently diagnosed versus chronic obstructive HCM.
Dave Fornell has covered healthcare for more than 17 years, with a focus in cardiology and radiology. Fornell is a 5-time winner of a Jesse H. Neal Award, the most prestigious editorial honors in the field of specialized journalism. The wins included best technical content, best use of social media and best COVID-19 coverage. Fornell was also a three-time Neal finalist for best range of work by a single author. He produces more than 100 editorial videos each year, most of them interviews with key opinion leaders in medicine. He also writes technical articles, covers key trends, conducts video hospital site visits, and is very involved with social media. E-mail: [email protected]