Aficamten outperforms in HCM trial

Cytokinetics, Incorporated announced positive topline results from MAPLE-HCM (Metoprolol vs Aficamten in Patients with LVOT Obstruction on Exercise Capacity in HCM), a Phase III clinical trial comparing aficamten as monotherapy to the standard of care beta blocker metoprolol as monotherapy in patients with symptomatic obstructive hypertrophic cardiomyopathy (HCM). MAPLE-HCM met its primary endpoint, demonstrating a statistically significant improvement in peak oxygen uptake (pVO2) from baseline to Week 24 for aficamten compared to metoprolol. The safety and tolerability profile of aficamten was favorable in comparison to metoprolol in MAPLE-HCM. The full results from MAPLE-HCM will be presented at an upcoming medical conference.

“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,” said Fady I. Malik, M.D., Ph.D., Cytokinetics’ Executive Vice President of Research & Development. “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.”

MAPLE-HCM: Clinical Trial Design: MAPLE-HCM was a Phase III, multi-center, randomized, double-blind active-comparator clinical trial of aficamten compared to metoprolol in patients with symptomatic obstructive HCM. The primary endpoint was the change in peak oxygen uptake (pVO2) from baseline to Week 24 measured by cardiopulmonary exercise testing (CPET). Secondary endpoints include the change from baseline to Week 24 in Kansas City Cardiomyopathy Questionnaire (KCCQ) score, the proportion of patients with ≥1 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.

MAPLE-HCM enrolled 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. At screening, patients enrolled in MAPLE-HCM had a resting LVOT-G ≥30 mmHg and/or post-Valsalva LVOT-G ≥50 mmHg in addition to left ventricular ejection fraction (LVEF) ≥ 60%, respiratory exchange ratio (RER) ≥ 1.05 and pVO2 <100% predicted, NYHA functional class II or III and a KCCQ Clinical Summary Score (KCCQ-CSS) score ≥ 35 and ≤ 90. Following the initial screening visit, all participants on standard of care (SOC) therapy underwent a washout period of up to 14 days to wean from SOC therapy, followed by an additional 7 days with no SOC therapy prior to the second screening visit. Each patient received up to four escalating doses of aficamten or metoprolol based on echocardiographic guidance as well as a matching placebo for the alternate therapy.

The development program for aficamten is assessing its potential as a treatment that improves exercise capacity as measured by peak oxygen uptake (pVO2) and relieves symptoms in patients with HCM. Aficamten was compared to placebo in SEQUOIA-HCM, a positive pivotal Phase III clinical trial demonstrating improvements in functional capacity, LVOT gradients, and heart failure symptoms in patients with symptomatic obstructive hypertrophic cardiomyopathy (HCM). Aficamten received Breakthrough Therapy Designation for the treatment of symptomatic obstructive HCM from the U.S. Food & Drug Administration (FDA) and from the National Medical Products Administration (NMPA) in China.

Aficamten is currently under regulatory review in the U.S by the FDA with a Prescription Drug User Fee Act (PDUFA) target action date of December 26, 2025. Additionally, the European Medicines Agency (EMA) is reviewing a Marketing Authorization Application (MAA) for aficamten, and The Center for Drug Evaluation (CDE) of the China National Medical Products Administration (NMPA) is reviewing an NDA for aficamten with Priority Review.

Aficamten is also currently being evaluated in ACACIA-HCM, a Phase III clinical trial of aficamten in patients with non-obstructive HCM; CEDAR-HCM, a clinical trial of aficamten in a pediatric population with obstructive HCM; and FOREST-HCM, an open-label extension clinical study of aficamten in patients with HCM.