Aficamten Shows Promise Over Metoprolol in Phase 3 MAPLE-HCM Trial for Obstructive HCM

Topline results were released from the phase 3 MAPLE-HCM trial, which compared aficamten with metoprolol in 175 adults with symptomatic obstructive hypertrophic cardiomyopathy (HCM). The trial results revealed that Aficamten Shows Promise Over Metoprolol for Obstructive HCM.The randomized, double-blind study focused on patients with left ventricular outflow tract obstruction and moderate functional impairment.

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 3, 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.

About Aficamten

Aficamten is an investigational selective, small molecule cardiac myosin inhibitor discovered following an extensive chemical optimization program that was conducted with careful attention to therapeutic index and pharmacokinetic properties and as may translate into next-in-class potential in clinical development. 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. In preclinical models, aficamten reduced myocardial contractility by binding directly to cardiac myosin at a distinct and selective allosteric binding site, thereby preventing myosin from entering a force producing state.

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 3 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 3 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.