Cytokinetics' Aficamten Hits Dual Phase III Endpoints in Non-Obstructive HCM

Cytokinetics’ Aficamten Hits Dual Phase III Endpoints in Non-Obstructive HCM

Aficamten met both Phase III ACACIA-HCM primary endpoints in 517 patients with symptomatic non-obstructive hypertrophic cardiomyopathy, improving patient-reported health status and peak oxygen consumption versus placebo.

The drug was generally well tolerated, but heart-failure events and treatment interruptions for reduced ejection fraction were more common with aficamten, particularly during dose titration.

Longer-term extension data suggested benefits were maintained beyond 96 weeks.

Cytokinetics plans to submit a supplemental FDA application for aficamten in non-obstructive HCM in the fourth quarter, expanding the drug’s potential beyond its obstructive HCM indication.

Cytokinetics NASDAQ: CYTK presented primary results from its Phase III ACACIA-HCM trial evaluating aficamten in patients with symptomatic non-obstructive hypertrophic cardiomyopathy, or nHCM, reporting that the study met its dual primary endpoints for patient-reported health status and exercise capacity.

The results were presented at a cardiology congress in Munich and were accompanied by publications in the New England Journal of Medicine and Circulation , according to Fady Malik, Cytokinetics’ executive vice president of research and development.

Malik said the company plans to submit a supplemental new drug application to the FDA for aficamten in nHCM later this year.

ACACIA-HCM enrolled 517 patients with symptomatic nHCM and randomized them equally to aficamten or placebo. Patients received aficamten doses ranging from 5 milligrams to 20 milligrams and were followed in a blinded manner for up to 72 weeks, including a four-week withdrawal period.

The primary analysis was conducted at week 36.

The trial’s dual primary endpoints were changes from baseline in the Kansas City Cardiomyopathy Questionnaire Clinical Summary Score, or KCCQ-CSS, and peak oxygen consumption, or peak VO2.

KCCQ-CSS improved by a placebo-adjusted 3 points at week 36 in favor of aficamten, with a P value of 0.021.

Peak VO2 improved by a placebo-adjusted 0.67 milliliters per kilogram per minute, with a P value of 0.003.

New York Heart Association class improvement of at least one class showed a 14% difference favoring aficamten at week 36, with a P value of less than 0.001.

The study also reported favorable results for a composite exercise Z-score and for NT-proBNP, a cardiac biomarker.

Treatment effects across prespecified subgroup analyses, including patients using beta blockers, those with intracavitary obstruction and those with differing genotype status, were generally consistent in favor of aficamten.

Among other secondary endpoints, aficamten showed an effect on left atrial volume index, though it did not reach statistical significance, with a P value of 0.058.

Time to first composite cardiovascular event did not differ between the aficamten and placebo groups.

More than 70% of aficamten-treated patients achieved a prespecified threshold for clinically meaningful symptom improvement, based on improvement in NYHA class and the Patient Global Impression of Change questionnaire.

About half achieved a defined improvement in exerci...