Cytokinetics Presents Additional Data from MAPLE-HCM at the Hypertrophic Cardiomyopathy Medical Society Scientific Sessions and American Heart Association Scientific Sessions 2025

Three Late Breaking Science Presentations from MAPLE-HCM Provide Additional Data Including Responder Analyses, Patient Reported Outcomes, and Cardiac Biomarkers 

SOUTH SAN FRANCISCO, Calif., Nov. 10, 2025 (GLOBE NEWSWIRE) -- Cytokinetics, Incorporated (Nasdaq: CYTK) today announced that additional data from MAPLE-HCM (Metoprolol vs Aficamten in Patients with LVOT Obstruction on Exercise Capacity in HCM) were presented in three Late Breaking Science sessions at the Hypertrophic Cardiomyopathy Medical Society Scientific Sessions and the American Heart Association Scientific Sessions 2025 in New Orleans, LA. Two of the presentations were simultaneously published in the Journal of the American College of Cardiology.^1,2

“These additional analyses from MAPLE-HCM expand on the primary finding that aficamten is superior to metoprolol on exercise capacity, with new insights into the overall treatment effect of aficamten as well as its effect on symptoms and biomarkers in comparison to metoprolol,” said Fady I. Malik, M.D., Ph.D., Cytokinetics’ Executive Vice President of Research & Development. “What’s notable is patients treated with aficamten achieved a significantly greater number of clinical response categories compared with metoprolol, and that nearly 40% achieved significant improvements in patient reported symptoms.”

Responder Analysis Shows Significantly More Patients on Aficamten Achieved Positive or Complete Response Compared to Metoprolol

Andrew Wang, M.D., Cardiologist and Professor of Medicine, Duke University School of Medicine presented a pre-specified responder analysis from MAPLE-HCM evaluating five clinically relevant measures of disease burden: complete hemodynamic response, symptom improvement, cardiac biomarker response, enhanced exercise capacity and favorable cardiac remodeling. These results were also simultaneously published in the Journal of the American College of Cardiology.¹

After 24 weeks of treatment, aficamten was associated with greater improvements than metoprolol in all outcome measures (all p<0.001) (Figure 1). Additionally, the proportion of patients who had a positive response (improvement in three or four clinical parameters) or a complete response (improvement in all five clinical parameters) was 78% in those receiving aficamten vs. 3% for those receiving metoprolol (p<0.001).

KCCQ, Kansas City Cardiomyopathy Questionnaire; LAVI, left atrial volume index; LVOT-G, left ventricular outflow tract gradient; NNT, number needed to treat; NT-proBNP, N-terminal pro–B-type natriuretic peptide; NYHA, New York Heart Association

As previously disclosed, in MAPLE-HCM the rate of adverse events (AEs) was similar between groups. At least one treatment-emergent AE was reported by 65 (73.9%) and 66 (75.9%) patients treated with aficamten and metoprolol, respectively. The most common AE reported in the aficamten group in excess of the comparator (>5%) was hypertension (9 [10.2%] patients on aficamten compared to 2 [2.3%] patients on metoprolol) and the most common AE reported in the metoprolol group in excess of the comparator was dizziness (15 [17.2%] patients on metoprolol compared to 5 [5.7%] patients on aficamten).

Analysis of Patient Reported Outcomes Expands on Effect of Aficamten on Patient Symptom Burden

Michael E. Nassif, M.D., Cardiologist, Saint Luke’s Mid America Heart Institute, Associate Professor of Medicine, University of Missouri Kansas City presented results from a pre-specified sub-study of two patient reported outcome instruments in MAPLE-HCM: the Kansas City Cardiomyopathy Questionnaire (KCCQ) and Seattle Angina Questionnaire Summary Score (SAQ). The results from this analysis were also simultaneously published in the Journal of the American College of Cardiology.²

At 24 weeks, treatment with aficamten resulted in significantly greater improvements than metoprolol in both KCCQ Overall Summary Score (KCCQ-OSS) (16.6 points vs. 8.9 points, respectively; between-group difference = 7.8 points [95% CI: 3.3 to 12.3; p=0.001]) and KCCQ Clinical Summary Score (KCCQ-CSS) (15.8 points vs. 8.7 points, respectively; between-group difference = 6.9 points [95% CI: 2.6 to 11.2; p=0.002]).

Aficamten was also associated with statistically significant improvements across all KCCQ domains (p<0.05). Patients on aficamten more frequently reported very large improvements in KCCQ-OSS, defined as ≥20-point improvement (38.6% vs. 18.4%; number needed to treat (NNT)=4.9), and were significantly less likely to experience a worsening in KCCQ-OSS than those treated with metoprolol (6.8% vs 18.4%; number needed to harm (NNH)=8.6).

A non-statistically significant trend for greater improvement in SAQ-SS was observed with aficamten (13.9 vs. 8.4 [adjusted between-group difference = 4.6 points; 95% CI: -0.3 to 9.5; p=0.063]), driven by a large and statistically significant improvement in the SAQ Physical Limitation Domain, where patients on aficamten improved by a mean of 18.7 points compared with 6.9 points for those on metoprolol (between-group difference = 10.1 points; 95% CI: 3.9 to 16.2; p=0.001). Changes in the SAQ Angina Frequency and Quality of Life Domains were similar between treatment groups.

Aficamten Associated with Statistically Significant Improvement in Cardiac Biomarkers Compared to Metoprolol

Neal K. Lakdawala, M.D., Cardiovascular Medicine, Brigham and Women’s Hospital, Harvard Medical School presented a pre-specified supplemental analysis from MAPLE-HCM of the impact of treatment with aficamten compared to metoprolol on the cardiac biomarkers NT-proBNP and high sensitivity cardiac troponin I (hs-cTnI). At baseline, high NT-proBNP and high hs-cTnI, indicative of cardiac wall stress and myocardial injury, respectively, were strongly correlated and generally associated with worse diastolic dysfunction. After treatment for 24 weeks, aficamten was associated with a 73% reduction (p<0.001) from baseline in NT-proBNP compared to an increase of 42% observed in patients receiving metoprolol (-81% treatment effect, p<0.001). Similarly, aficamten was associated with a 43% reduction in hs-cTnI, compared to a 17% decrease for metoprolol (-28% treatment effect, p=0.001). Patients with the greatest reductions in NT-proBNP experienced greater improvements in peak oxygen uptake (pVO₂) and ventilatory efficiency (VE/VCO₂). Additionally, changes in NT-proBNP were correlated with reductions of left ventricular outflow tract gradients (LVOT-G) and improved health status (KCCQ-OSS).

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.³ 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 evaluated in SEQUOIA-HCM, a positive pivotal Phase 3 clinical trial in patients with symptomatic obstructive hypertrophic cardiomyopathy (HCM). Aficamten received Breakthrough Therapy Designation for the treatment of symptomatic HCM from the U.S. Food & Drug Administration (FDA) and for the treatment of symptomatic obstructive HCM from the National Medical Products Administration (NMPA) in China.

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 oHCM; and FOREST-HCM, an open-label extension clinical study of aficamten in patients with HCM.

Disclaimer

This communication contains a summary of new data related to the clinical development of aficamten presented at the Hypertrophic Cardiomyopathy Medical Society Scientific Sessions and the American Heart Association Scientific Sessions 2025. Aficamten is an investigational drug and is not approved by any regulatory agency. Its safety and efficacy have not been established. Aficamten is currently under regulatory review in the U.S, where the FDA is reviewing a New Drug Application (NDA) for aficamten 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.

About Hypertrophic Cardiomyopathy

Hypertrophic cardiomyopathy (HCM) is a disease in which the heart muscle (myoc