(P1) Cytokinetics, Incorporated (Nasdaq: CYTK) announced its pivotal Phase 3 trial for aficamten in non-obstructive hypertrophic cardiomyopathy (nHCM) met both of its primary endpoints, though the company’s stock fell 3.1% on the news.
(P2) “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,” said Fady I. Malik, M.D., Ph.D., Cytokinetics’ Executive Vice President of Research & Development.
(P3) The ACACIA-HCM study showed a statistically significant improvement in the Kansas City Cardiomyopathy Questionnaire Clinical Summary Score (KCCQ-CSS) with a least square mean difference of 3.0 compared to placebo (p=0.021), indicating better patient-reported symptom burden. The trial also met its other primary endpoint for maximal exercise performance (pVO2), showing a difference of 0.67 mL/kg/min versus placebo (p=0.003). Key secondary endpoints, including improvements in NYHA Functional Class and reductions in the biomarker NT-proBNP, were also met with high statistical significance (p<0.001).
(P4) The positive data positions aficamten as a potential first-in-class therapy for nHCM, a condition with no currently approved treatments targeting its underlying cause. However, the market’s reaction was tempered by safety data, which showed that 10% of participants taking aficamten experienced a drop in left ventricular ejection fraction (LVEF) to below 50%, compared to just 1% on placebo.
The trial, ACACIA-HCM, was a multi-center, randomized, double-blind, placebo-controlled study that enrolled 516 participants. Patients were treated with aficamten or placebo for up to 72 weeks. The company reported no new safety signals were identified during the trial. However, two participants on aficamten experienced a serious adverse event of heart failure associated with LVEF dropping below 50%, and treatment was interrupted in 3% of patients on the drug due to LVEF falling below 40%.
Aficamten, which is marketed as MYQORZO® for the separate condition of obstructive hypertrophic cardiomyopathy (oHCM), is a cardiac myosin inhibitor designed to reduce the heart muscle's hypercontractility.
The results provide a clear path for regulatory discussions, potentially expanding aficamten's label to a broader patient population. Cytokinetics plans to present the full results from ACACIA-HCM at an upcoming medical meeting and discuss them with the U.S. Food and Drug Administration.
This article is for informational purposes only and does not constitute investment advice.
