Cytokinetics hits on both primary endpoints in pivotal non-obstructive HCM trial

Cytokinetics has reported positive topline results from ACACIA-HCM, its pivotal Phase 3 trial of aficamten in patients with symptomatic non-obstructive hypertrophic cardiomyopathy (HCM). The trial cleared both dual primary endpoints, showing statistically significant gains over placebo in patient-reported symptom burden and maximal exercise capacity at week 36.

Fady Malik, executive vice president of research and development at Cytokinetics, underscored what the result means for a patient population with no approved options: “Patients with non-obstructive HCM have no therapies approved to treat the underlying hypercontractility associated with the disease. We hope that will change with ACACIA-HCM which is the first clinical trial to demonstrate statistically significant improvements in exercise capacity and symptom burden in patients with non-obstructive HCM. We believe that the totality and consistency of evidence favoring aficamten across multiple patient-reported and physician-assessed endpoints of symptom improvement and physical function are clinically meaningful for patients with non-obstructive HCM.”

the primary endpoint results

Both primary endpoints were met with statistical significance at week 36 compared to placebo:

• KCCQ-CSS (Kansas City Cardiomyopathy Questionnaire Clinical Summary Score): aficamten +11.4 vs. placebo +8.4; treatment difference of 3.0 points (95% CI: 0.5–5.5; p=0.021)
• pVO2 (maximal exercise performance): aficamten +0.64 mL/kg/min vs. placebo -0.03 mL/kg/min; treatment difference of 0.67 mL/kg/min (95% CI: 0.22–1.1; p=0.003)

KCCQ improvements were sustained throughout the treatment period, then reversed toward placebo levels following washout — suggesting an on-target effect. The pVO2 improvement mirrors patterns seen in prior aficamten trials in obstructive HCM.

secondary endpoints and safety

All three key secondary endpoints reached statistical significance (p<0.001), including the proportion of patients improving by at least one NYHA functional class, a composite z-score of ventilatory efficiency and pVO2, and NT-proBNP levels.

On safety, no new signals emerged and trial completion rates were similar across both arms (aficamten 88.4% vs. placebo 90.3%). Left ventricular ejection fraction below 50% occurred in 10% of aficamten patients versus 1% on placebo. Two patients on aficamten experienced a serious adverse event of heart failure linked to LVEF falling below 50%, and 3% required treatment interruptions due to LVEF dropping under 40%.

Dr. Malik closed with a look ahead: “We are grateful to the clinical trial investigators and staff, as well as the patients who participated in this trial. We look forward to presenting the results from ACACIA-HCM at an upcoming medical meeting, as well as discussing them with the U.S. FDA and other regulatory authorities.”

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Related Topics and Keywords

Cytokinetics, non-obstructive HCM trial, ODYSSEY-HCM Trial, Phase 3 ODYSSEY-HCM Trial