Myosin Inhibitors in Hypertrophic Cardiomyopathy (HCM) – ESC 2025
Myosin Inhibitors in Hypertrophic Cardiomyopathy (HCM) – ESC 2025
Source: Medical News | ESC 2025 | August 30, 2025
1. Background
• Myosin inhibitors (aficamten, mavacamten) target excessive contractility in HCM.
• Current guidelines: beta-blockers are first-line for obstructive HCM; no approved therapies for non-obstructive HCM.
2. MAPLE-HCM (Phase 3, obstructive HCM)
• Design: 175 symptomatic patients, LVEF ≥60%, randomized to aficamten vs metoprolol.
• Primary endpoint: Change in peak VO₂.
• Results:
• +2.3 mL/kg/min improvement with aficamten vs decline with beta-blockers (P<.001).
• Significant improvements in: NYHA functional class, KCCQ score, NT-proBNP, and LVOT gradient.
• Benefits consistent across all subgroups.
• Implication: First controlled evidence that a myosin inhibitor is superior to beta-blockers as first-line therapy → may change guidelines if approved.
3. ODYSSEY-HCM (Phase 3, non-obstructive HCM)
• Design: 289 patients, randomized mavacamten vs placebo, 48 weeks.
• Results:
• Primary endpoints (peak VO₂, KCCQ score) not met (P=0.07 and 0.06).
• NT-proBNP reduced and small improvements in NYHA class observed, but nonsignificant.
• Higher treatment interruption due to AEs in the mavacamten group (14.6% vs 5.2%).
• Implication: No proven benefit for mavacamten in non-obstructive HCM; disease remains a major unmet need.
4. Overall Takeaways
• Aficamten: Positive, may shift first-line therapy for obstructive HCM ahead of beta-blockers.
• Mavacamten: Failed in non-obstructive HCM despite prior promise; further studies needed.
• Guideline impact: ESC experts suggested MAPLE-HCM results could lead to revised treatment sequence for obstructive HCM.