Cytokinetics Reveals Phase 1 CK-4021586 Study Results
May 08, 2024 – Cytokinetics, Incorporated (Nasdaq: CYTK) has announced promising topline results from its Phase 1 trial of CK-4021586 (CK-586). This study successfully achieved its primary and secondary goals, which were to evaluate the safety, tolerability, and pharmacokinetics (PK) of CK-586 administered orally in both single and multiple doses. The findings pave the way for a Phase 2 clinical trial involving patients with heart failure with preserved ejection fraction (HFpEF), scheduled to commence in the fourth quarter of 2024. CK-586 is under development as a cardiac myosin inhibitor for potentially treating a specific subset of HFpEF patients.
“These findings underscore CK-586’s potential as a treatment targeting the underlying hypercontractility in HFpEF patients,” said Fady I. Malik, M.D., Ph.D., Executive Vice President of Research and Development at Cytokinetics. “Following the positive Phase 2 results of aficamten in patients with non-obstructive HCM, we are confident in applying this approach to HFpEF. We are eagerly anticipating the start of the Phase 2 clinical trial for CK-586 in the fourth quarter, which will further expand our cardiac myosin-directed development platform focused on specialized cardiology indications.”
Phase 1 Design and Key Findings
The Phase 1 trial was a double-blind, randomized, placebo-controlled, multi-part study designed to assess the safety, tolerability, and PK of orally administered CK-586 in healthy participants. The trial included seven single ascending dose cohorts ranging from 10 mg to 600 mg, involving 10 participants each, and two multiple-dose ascending cohorts (100 mg and 200 mg once daily), also involving 10 participants each. The study met its primary objective, demonstrating that CK-586 is safe and well tolerated with linear PK in healthy subjects. Pharmacodynamics, evaluated via echocardiography, aligned with expectations, and no serious adverse events were reported. The study did not reach any stopping criteria.
About CK-4021586 (CK-586)
CK-4021586 (CK-586) is a novel, selective, oral, small molecule cardiac myosin inhibitor designed to mitigate hypercontractility linked with HFpEF. In preclinical models, CK-586 reduced cardiac hypercontractility by lowering the number of active myosin cross-bridges during cardiac contraction, thus reducing contractile force without affecting calcium transients. HFpEF can resemble non-obstructive hypertrophic cardiomyopathy (HCM), presenting with higher ejection fractions, thickened heart walls, elevated biomarkers, and heart failure symptoms. Aficamten, another cardiac myosin inhibitor developed by Cytokinetics, demonstrated positive outcomes in a Phase 2 clinical trial for non-obstructive HCM, including improved patient-reported outcomes and biomarkers, supporting this mechanism for HFpEF as well.
About Heart Failure
Heart failure affects more than 64 million people globally, with about 6.7 million cases in the United States alone, projected to rise to over 8.5 million by 2030. Nearly half of heart failure patients have HFpEF, and its prevalence is on the rise. Alarmingly, around 75% of HFpEF patients will die within five years of their first hospitalization, and 84% will be rehospitalized. Despite advances in treatment, the prognosis for heart failure remains dire.
About Cytokinetics
Cytokinetics is a specialty cardiovascular biopharmaceutical company dedicated to discovering, developing, and commercializing first-in-class muscle activators and next-in-class muscle inhibitors for diseases where cardiac muscle performance is compromised. As a leader in muscle biology, Cytokinetics is advancing small molecule drug candidates designed to impact myocardial muscle function and contractility. The company is preparing regulatory submissions for aficamten, following positive results from a pivotal Phase 3 trial in obstructive HCM. Other ongoing trials include evaluations of aficamten in various HCM populations and the development of omecamtiv mecarbil and CK-136 for different types of heart failure.
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