A prespecified, secondary analysis of the MAPLE-HCM trial has shown that aficamten monotherapy provides superior and rapid benefits across multiple domains of disease burden compared with metoprolol in patients with symptomatic obstructive hypertrophic cardiomyopathy (oHCM).¹ Aficamten is a next-in-class cardiac myosin inhibitor (CMI) designed to reduce myocardial hypercontractility by decreasing the number of active actin-myosin cross-bridges, thereby addressing the fundamental pathophysiology in oHCM.
Study Details
The MAPLE-HCM trial (NCT05767346) was a Phase 3, international, double-blind, double-dummy, randomised trial. It enrolled 175 adults with symptomatic oHCM and a left ventricular outflow tract gradient (LVOT-G) of ≥30 mm Hg at rest and/or ≥50 mm Hg with Valsalva. Patients were assigned 1:1 to receive either aficamten (n=88) or metoprolol (n=87) once daily for 24 weeks. The analysis assessed clinical response across five domains: complete haemodynamic response (LVOT-G <30 mm Hg rest and <50 mm Hg Valsalva); symptom improvement (≥1 NYHA class improvement and/or ≥10-point KCCQ-CSS improvement); cardiac biomarker response (≥50% NT-proBNP decrease); enhanced exercise capacity (≥1.0 mL/kg/min pVO₂ increase); and favourable cardiac remodelling (≥10% LAVI decrease).¹
Key Findings
At 24 weeks, patients treated with aficamten demonstrated significantly greater benefits across all efficacy measures. A complete haemodynamic response was achieved in 72% of the aficamten group versus 25% of the metoprolol group (OR: 7.5; P<0.001). Symptom improvement was seen in 76% of aficamten patients compared to 56% of metoprolol patients (OR: 2.5; P=0.005). Furthermore, a ≥50% reduction in NT-proBNP was observed in 72% of the aficamten arm versus just 5% of the metoprolol arm. An increase in pVO₂ of ≥1.0 mL/kg/min occurred in 40% of aficamten patients versus 15% of those on metoprolol (OR: 3.8; P<0.001). Overall, 78% of patients on aficamten were classified as positive or complete responders (achieving ≥3 outcomes), compared with only 3% of patients on metoprolol (P<0.001).¹
Conclusion
The findings from this multidomain, patient-level evaluation show that aficamten monotherapy leads to broad and rapid improvements across multiple clinically relevant measures of disease burden in oHCM when compared to the current first-line therapy, metoprolol. These observations support the emerging role of aficamten as a monotherapy for this condition.
The stability of these outcomes with longer-term aficamten treatment will be assessed in the ongoing FOREST-HCM trial.
This study was funded by Cytokinetics, Incorporated.
Disclaimer
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References
1. Wang A, Garcia-Pavia P, Masri A, et al. Aficamten in Obstructive Hypertrophic Cardiomyopathy: A Multidomain, Patient-Level Analysis of the MAPLE-HCM Trial. JACC. 2026;87(8):1029-1042. https://doi.org/10.1016/j.jacc.2025.10.057
2. Garcia-Pavia P, Maron MS, Masri A, et al. Aficamten or metoprolol monotherapy for obstructive hypertrophic cardiomyopathy. N Engl J Med. 2025;393(10):949-960. https://doi.org/10.1056/NEJMoa2504654