Cytokinetics' Aficamten Achieves Landmark Phase 3 Win in Non-Obstructive Hypertrophic Cardiomyopathy
On August 28, 2026, Cytokinetics, Incorporated announced positive primary results from its pivotal Phase 3 ACACIA-HCM trial (NCT06081894) evaluating aficamten (already approved as MYQORZO for obstructive HCM) in patients with symptomatic non-obstructive hypertrophic cardiomyopathy (nHCM). The results were presented at a Hot Line session of the European Society of Cardiology (ESC) Congress 2026 in Munich, Germany, and simultaneously published in The New England Journal of Medicine.
Symptomatic nHCM affects roughly half of all HCM patients globally and is associated with severe diastolic dysfunction, exercise limitation, and heart failure, but currently has no approved pharmacological therapies. Aficamten directly targets excess myocardial contractility and diastolic impairment.
The trial randomized 517 patients with symptomatic nHCM (1:1 ratio) to receive either aficamten (starting at 5 mg, titrated up to 20 mg once daily) or placebo for 36 weeks. The trial successfully met both of its dual primary endpoints:
- Kansas City Cardiomyopathy Questionnaire Clinical Summary Score (KCCQ-CSS): Aficamten improved KCCQ-CSS by +11.4 points from baseline compared to +8.4 points for placebo (treatment difference of +3.0 points, p=0.021).
- Peak Oxygen Consumption (pVO2): Aficamten improved pVO2 by +0.64 ml/kg/min compared to -0.03 for placebo (treatment difference of +0.67 ml/kg/min, p=0.003).
In safety findings, aficamten was generally well-tolerated. A drop in left ventricular ejection fraction (LVEF) below 50% occurred in 10.5% of aficamten patients compared to 0.8% of placebo patients, with two patients experiencing serious heart failure events associated with LVEF <50%. Both events resolved with standard diuretic treatment.
Based on these positive results, Cytokinetics plans to submit a supplemental New Drug Application (sNDA) to the FDA for aficamten in symptomatic nHCM in the fourth quarter of 2026.
Verbatim Quotes
"ACACIA-HCM is the first-ever positive clinical trial in non-obstructive HCM," said Stephen Heitner, M.D., Cytokinetics’ Chief Medical Officer. "If approved, we look forward to seeing aficamten become the first cardiac myosin inhibitor to treat the full spectrum of symptomatic HCM."
"Among patients with symptomatic nonobstructive HCM, treatment with aficamten resulted in a significantly greater change in exercise capacity and patient-reported health status than placebo at 36 weeks." (NEJM)