Cytokinetics said its phase 3 Acacia-HCM trial in symptomatic non-obstructive hypertrophic cardiomyopathy met both primary endpoints at 36 weeks, with aficamten beating placebo on patient-reported symptoms and exercise performance.
On the Kansas City Cardiomyopathy Questionnaire clinical summary score, aficamten improved by 11.4 points from baseline versus 8.4 points for placebo, a treatment difference of 3.0 points and a p-value of 0.021. On maximal exercise performance, measured by pVO2, aficamten rose 0.64 ml/kg/min from baseline while placebo fell 0.03 ml/kg/min, producing a 0.67 ml/kg/min treatment difference with a p-value of 0.003.
The trial enrolled and treated 517 participants outside Japan on a 1:1 basis with aficamten or placebo. The company said the baseline characteristics were well matched between groups.
Several secondary measures also favored aficamten. At week 36, 41.9% of patients on aficamten improved by at least one New York Heart Association class, compared with 27.8% on placebo, a 14.1-point gap. The composite z-score of two cardiopulmonary exercise testing measures improved 0.14 points more than placebo, and NT-proBNP showed a proportional treatment difference of 0.43 versus placebo, both with p-values below 0.001.
Not every endpoint moved in the same direction. Change in left atrial volume index missed statistical significance with a p-value of 0.058, and time to first cardiovascular event was 68.2 weeks on aficamten versus 68.8 weeks on placebo, a difference of 0.6 weeks and a p-value of 0.678.
Safety data showed higher discontinuation and higher serious adverse event rates with aficamten. Non-fatal adverse events leading to early study-drug discontinuation occurred in 18 patients, or 7.0%, on aficamten versus 5 patients, or 1.9%, on placebo. Serious adverse events were reported in 52 patients, or 20.2%, on aficamten compared with 38 patients, or 14.7%, on placebo.
Left ventricular ejection fraction below 50% occurred in 27 patients, or 10.5%, on aficamten and 2 patients, or 0.8%, on placebo. The company also said 2 patients on aficamten had serious heart failure events associated with LVEF below 50%, while 10 additional aficamten patients had serious heart failure events not associated with LVEF below 50%, versus 3 such patients on placebo.
Cytokinetics said it plans to submit a supplemental new drug application to the FDA in the fourth quarter of 2026. In a separate global efficacy analysis, the company said aficamten improved all five measured domains versus placebo at 36 weeks, with 53% of patients showing a clinical response in three or more outcome measures compared with 13% on placebo. Following these announcements, the company's shares moved -5.01%, and are now trading at a price of $73.995. For the full picture, make sure to review CYTOKINETICS INC's 8-K report.
