Cytokinetics' Aficamten Meets Both Primary Goals in Phase 3 Non-Obstructive HCM Trial

Cytokinetics said on May 5 that aficamten met both of its primary endpoints in ACACIA-HCM, a pivotal Phase 3 trial in people with symptomatic non-obstructive hypertrophic cardiomyopathy (HCM), according to the company's announcement, distributed by GlobeNewswire and read via The Manila Times.

The figures are company-reported topline results. They have not yet been presented at a medical meeting or published in a journal.

The ACACIA-HCM results

ACACIA-HCM was a multi-center, randomized, double-blind, placebo-controlled trial that randomized and treated 516 participants outside Japan on a 1:1 basis to aficamten or placebo. Its dual primary endpoint was the change from baseline to Week 36 in the Kansas City Cardiomyopathy Questionnaire Clinical Summary Score (KCCQ-CSS), a patient-reported measure of symptoms and physical limits, and in peak oxygen uptake (pVO2), a measure of maximal exercise performance.

On KCCQ-CSS, participants on aficamten improved by a least-squares mean of 11.4 points versus 8.4 points on placebo, a difference of 3.0 points (p=0.021), the company said. Peak oxygen uptake rose by 0.64 mL/kg/min on aficamten and was essentially unchanged on placebo (-0.03), a difference of 0.67 mL/kg/min (p=0.003).

According to the release, the KCCQ improvement held through the treatment period, and after a washout the scores of participants who had taken aficamten fell back to match the placebo group. The company also reported consistent findings on secondary endpoints including New York Heart Association functional class and NT-proBNP, a blood marker of heart strain.

"Patients with non-obstructive HCM have no therapies approved to treat the underlying hypercontractility associated with the disease," said Fady I. Malik, Cytokinetics' executive vice president of research and development.

Safety

The company said no new safety signals were identified. Similar shares of participants completed planned dosing on aficamten and placebo (88.4% and 90.3%). Two participants on aficamten had a serious adverse event of heart failure associated with reduced left ventricular ejection fraction, according to the release.

Aficamten is a cardiac myosin inhibitor that reduces the force of heart muscle contraction. In the trial, doses were raised step by step under echocardiographic guidance, and only when a participant's ejection fraction was at least 60%.

Approved use and next steps

The drug is already sold as Myqorzo for symptomatic obstructive HCM, in which thickened heart muscle blocks blood flow out of the heart. Tablets & Capsules reported that the FDA approved the tablets for that use in December 2025. The company's release says Myqorzo is approved in the US, China and the European Union for obstructive HCM. Its US label carries a boxed warning on the risk of heart failure, and the drug is available only through a restricted safety program.

Non-obstructive HCM, in which the heart muscle is thickened without that blockage, is not part of any approval. Cytokinetics said it plans to present the ACACIA-HCM results at an upcoming medical meeting and to discuss them with the FDA and other regulatory authorities. The trial continued treatment for up to 72 weeks to assess further endpoints, including time to first cardiovascular event.