Cytokinetics reported positive topline results from the Phase 3 ACACIA-HCM trial, with aficamten meeting both dual primary endpoints in patients with symptomatic non-obstructive hypertrophic cardiomyopathy and demonstrating significant improvements in symptom burden and exercise capacity versus placebo.
Written By: Farha Farheen, PharmD
Reviewed By: Pharmacally Editorial Team
Cytokinetics has announced positive topline results from the Phase 3 ACACIA‑HCM trial evaluating aficamten in patients with symptomatic non‑obstructive hypertrophic cardiomyopathy (nHCM), meeting both dual primary endpoints and demonstrating statistically significant improvements in exercise capacity and symptom burden versus placebo.
Trial design and endpoints
The ACACIA‑HCM trial (NCT06081894) was a randomized, double‑blind, placebo‑controlled study that enrolled 516 participants with symptomatic nHCM at sites outside Japan and evaluated aficamten over 36 weeks.
The dual primary endpoints were 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 limitations, and change from baseline to Week 36 in peak oxygen uptake (pVO₂), an indicator of maximal exercise performance.
Efficacy results
Aficamten achieved a statistically significant improvement in KCCQ‑CSS versus placebo, with a placebo‑adjusted least squares mean difference of 3.0 points at Week 36 (p=0.021). Peak oxygen uptake (pVO₂) improved by a placebo‑adjusted least squares mean difference of 0.67 mL/kg/min (p=0.003), indicating improved exercise capacity.
Cytokinetics reported that improvements in KCCQ scores were maintained throughout treatment and declined after washout, returning toward placebo levels, supporting an on‑drug treatment effect.
Fady I. Malik, M.D., Ph.D., Executive Vice President of Research & Development at Cytokinetics, said the ACACIA-HCM findings support aficamten’s potential to address the underlying hypercontractility associated with non-obstructive HCM, highlighting improvements across exercise capacity, symptom burden, and multiple patient- and physician-assessed measures of physical function.
Secondary endpoints
The trial met several key secondary endpoints, including statistically significant improvements in New York Heart Association (NYHA) functional class and ventilatory efficiency (VE/VCO₂ slope), as well as reductions in NT‑proBNP, a biomarker associated with cardiac stress.
These findings suggest that aficamten may modify underlying pathophysiology in addition to improving functional and symptomatic outcomes in nHCM.
Safety and tolerability
No new safety signals were identified in the study. Completion rates were similar between the aficamten and placebo groups, with the majority of participants completing the 36‑week double‑blind period. Left ventricular ejection fraction (LVEF) below 50% occurred in 10% of participants receiving aficamten compared with 1% in the placebo arm.
Two patients receiving aficamten experienced serious adverse events of heart failure associated with reduced LVEF, and treatment interruptions due to LVEF below 40% occurred in 3% of treated participants.
Context and implications
Non‑obstructive hypertrophic cardiomyopathy currently has no approved disease‑modifying therapies. Aficamten (marketed as MYQORZO for obstructive HCM in the United States, European Union, and China) is a selective cardiac myosin inhibitor designed to reduce excessive myocardial contractility.
Based on these ACACIA‑HCM results, Cytokinetics plans to present detailed trial data at an upcoming medical meeting and to discuss the findings with the U.S. FDA and other regulatory authorities as part of potential regulatory submissions for aficamten in nHCM.
Reference
About the Writer
Farha Farheen, PharmD, is a pharmacy professional with a strong interest in pharmacovigilance and clinical research. She has completed her Doctor of Pharmacy (Pharm.D) along with her internship as a Clinical Pharmacist. She has hands-on experience in adverse drug reaction (ADR) reporting, safety data documentation, and pharmacovigilance workflows, and is proficient in using VigiFlow. She is also a patent holder for an antibacterial formulation enriched with bioactive substances, granted by the German Patent and Trademark Office.