Cytokinetics Announces Topline Data From Phase 1 Clinical Study of CK-4021586

Rhea-AI Summary

Cytokinetics announced topline data from the Phase 1 clinical study of CK-4021586 (CK-586), showing positive results in safety, tolerability, and pharmacokinetics. The data support the advancement to a Phase 2 clinical trial in patients with heart failure with preserved ejection fraction (HFpEF) starting in Q4 2024. CK-586, a cardiac myosin inhibitor, aims to treat a subgroup of HFpEF patients by addressing underlying hypercontractility. The study met its primary and secondary objectives, with no serious adverse events observed.

Positive

• CK-586 showed positive results in safety, tolerability, and pharmacokinetics, supporting its advancement to a Phase 2 clinical trial in HFpEF patients.
• The study met its primary and secondary objectives, demonstrating the safety and well-tolerance of CK-586 in healthy participants with linear PK.
• No serious adverse events were observed during the Phase 1 study of CK-586.

Negative

• None.

Data Support Advancement to Phase 2 Clinical Trial in Patients with Heart Failure with Preserved Ejection Fraction Expected to Begin in Q4 2024

Full Data from the Phase 1 Study to be Presented at a Medical Congress in 2H 2024

SOUTH SAN FRANCISCO, Calif., May 08, 2024 (GLOBE NEWSWIRE) -- Cytokinetics, Incorporated (Nasdaq: CYTK) today announced topline data from the Phase 1 study of CK-4021586 (CK-586). The study met its primary and secondary objectives to assess the safety, tolerability and pharmacokinetics (PK) of single and multiple oral doses of CK-586. The data support the advancement of CK-586 to a Phase 2 clinical trial in patients with heart failure with preserved ejection fraction (HFpEF) which is expected to begin in Q4 2024. CK-586 is a cardiac myosin inhibitor in development for the potential treatment of a subgroup of patients with HFpEF.

“These data reinforce the potential of CK-586 as a drug candidate designed to directly impact the underlying hypercontractility in a subset of patients with HFpEF,” said Fady I. Malik, M.D., Ph.D., Cytokinetics’ Executive Vice President, Research and Development. “Based on previously reported positive Phase 2 results of aficamten in patients with non-obstructive HCM, we are confident in this approach in HFpEF as the conditions have a similar profile. We look forward to starting the Phase 2 clinical trial of CK-586 in the fourth quarter, further extending the potential of our cardiac myosin directed development platform focused to specialty cardiology indications.”

Phase 1 Design and Key Findings

The primary objective of this Phase 1 double-blind randomized, placebo-controlled, multi-part single and multiple ascending dose clinical study was to evaluate the safety, tolerability and PK of CK-586 when administered orally as single or multiple doses to healthy participants. The study design included seven single ascending dose cohorts (10 mg to 600 mg) comprised of 10 participants each, and two multiple-dose ascending cohorts (100 and 200 mg once daily) comprised of 10 participants each. The study met the primary objective, demonstrating that CK-586 was safe and well tolerated in healthy participants with linear PK. Pharmacodynamics were evaluated using echocardiography and consistent with expectations. No serious adverse events were observed, and the stopping criteria were not met in the study.

About CK-4021586 (CK-586)

CK-4021586 (CK-586) is a novel, selective, oral, small molecule cardiac myosin inhibitor designed to reduce the hypercontractility associated with heart failure with preserved ejection fraction (HFpEF). In preclinical models, CK-586 reduced cardiac hypercontractility by decreasing the number of active myosin cross-bridges during cardiac contraction thereby reducing the contractile force, without effect on calcium transients. In some patients, HFpEF is a condition that resembles non-obstructive hypertrophic cardiomyopathy (HCM) in that the patients have higher ejection fractions, thickened walls of their heart, elevated biomarkers, and symptoms of heart failure. In a Phase 2 clinical trial in patients with non-obstructive HCM, aficamten, a cardiac myosin inhibitor also developed by the Company, was well tolerated, improved patient reported outcomes (Kansas City Cardiomyopathy Questionnaire (KCCQ) and New York Heart Association (NYHA) Functional Class) and biomarkers, measures that are also relevant to HFpEF, lending support for this mechanism of action in HFpEF.

About Heart Failure

Heart failure is a grievous condition that affects more than 64 million people worldwide.¹ Approximately 6.7 million Americans have heart failure, which is expected to increase to over 8.5 million Americans by 2030.² Approximately half of patients with heart failure have heart failure with preserved ejection fraction (HFpEF)³, and the prevalence of HFpEF is increasing.^2,4 Approximately 75% of patients with HFpEF will die within five years of initial hospitalization, and 84% will be rehospitalized.² Despite broad use of standard treatments and advances in care, the prognosis for patients with heart failure is poor.⁵

About Cytokinetics

Cytokinetics is a late-stage, specialty cardiovascular biopharmaceutical company focused on discovering, developing and commercializing first-in-class muscle activators and next-in-class muscle inhibitors as potential treatments for debilitating diseases in which cardiac muscle performance is compromised. As a leader in muscle biology and the mechanics of muscle performance, the company is developing small molecule drug candidates specifically engineered to impact myocardial muscle function and contractility. Cytokinetics is preparing for regulatory submissions for aficamten, its next-in-class cardiac myosin inhibitor, following positive results from SEQUOIA-HCM, the pivotal Phase 3 clinical trial in obstructive hypertrophic cardiomyopathy. Aficamten is also currently being evaluated in MAPLE-HCM, a Phase 3 clinical trial of aficamten as monotherapy compared to metoprolol as monotherapy in patients with obstructive HCM, ACACIA-HCM, a Phase 3 clinical trial of aficamten in patients with non-obstructive HCM, CEDAR-HCM, a clinical trial of aficamten in a pediatric population with obstructive HCM, and FOREST-HCM, an open-label extension clinical study of aficamten in patients with HCM. Cytokinetics is also developing omecamtiv mecarbil, a cardiac muscle activator, in patients with heart failure. Additionally, Cytokinetics is developing CK-586, a cardiac myosin inhibitor with a mechanism of action distinct from aficamten for the potential treatment of HFpEF, and CK-136, a cardiac troponin activator for the potential treatment HFrEF and other types of heart failure, such as right ventricular failure resulting from impaired cardiac contractility.

For additional information about Cytokinetics, visit www.cytokinetics.com and follow us on X, LinkedIn, Facebook and YouTube.

Forward-Looking Statements

This press release contains forward-looking statements for purposes of the Private Securities Litigation Reform Act of 1995 (the “Act”). Cytokinetics disclaims any intent or obligation to update these forward-looking statements and claims the protection of the Act's Safe Harbor for forward-looking statements. Examples of such statements include, but are not limited to, statements, express or implied, relating to the potential benefits of CK-586 for patients with heart failure with preserved ejection fraction (HFpEF) and our ability to commence a Phase 2 clinical trial of CK-586 in the fourth quarter of 2024, if ever. Such statements are based on management's current expectations, but actual results may differ materially due to various risks and uncertainties, including, but not limited to, potential difficulties or delays in the development, testing, regulatory approvals for trial commencement, progression or product sale or manufacturing, or production of Cytokinetics' drug candidates that could slow or prevent clinical development or product approval; Cytokinetics' drug candidates may have adverse side effects or inadequate therapeutic efficacy; the FDA or foreign regulatory agencies may delay or limit Cytokinetics' ability to conduct clinical trials; Cytokinetics may be unable to obtain or maintain patent or trade secret protection for its intellectual property; standards of care may change, rendering Cytokinetics' drug candidates obsolete; and competitive products or alternative therapies may be developed by others for the treatment of indications Cytokinetics' drug candidates and potential drug candidates may target. For further information regarding these and other risks related to Cytokinetics' business, investors should consult Cytokinetics' filings with the Securities and Exchange Commission.

CYTOKINETICS® and the C-shaped logo are registered trademarks of Cytokinetics in the U.S. and certain other countries.

Contact:
Cytokinetics
Diane Weiser
Senior Vice President, Corporate Affairs
(415) 290-7757

References:

1. James et al. GBD 2017 Disease and Injury Incidence and Prevalence Collaborators. Lancet 2018; 392: 1789–858.
2. Bozkurt B, Ahmad T, Alexander KM, Baker WL, Bosak K, Breathett K, Fonarow GC, Heidenreich P, Ho JE, Hsich E, Ibrahim NE, Jones LM, Khan SS, Khazanie P, Koelling T, Krumholz HM, Khush KK, Lee C, Morris AA, Page RL 2nd, Pandey A, Piano MR, Stehlik J, Stevenson LW, Teerlink JR, Vaduganathan M, Ziaeian B; Writing Committee Members. Heart Failure Epidemiology and Outcomes Statistics: A Report of the Heart Failure Society of America. J Card Fail. 2023 Oct;29(10):1412-1451. doi: 10.1016/j.cardfail.2023.07.006. Epub 2023 Sep 26. PMID: 37797885; PMCID: PMC10864030.
3. Dunlay SM, Roger VL, Weston SA, Jiang R, Redfield MM. Longitudinal changes in ejection fraction in heart failure patients with preserved and reduced ejection fraction. Circ Heart Fail. 2012 Nov;5(6):720-6. doi: 10.1161/CIRCHEARTFAILURE.111.966366. Epub 2012 Aug 30. PMID: 22936826; PMCID: PMC3661289.
4. Yancy CW, Jessup M, Bozkurt B, et al. 2013 ACCF/AHA Guideline for the Management of Heart failure: A Report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines. Circulation. 2013;128:e240-e327. 
5. Jhund PS, MacIntyre K, Simpson CR, et al. Long-Term Trends in First Hospitalization for Heart Failure and Subsequent Survival Between 1986 and 2003. Circulation. 2009;119:515-523.
   

FAQ

What is the Phase 1 clinical study of CK-4021586 about?

The Phase 1 clinical study of CK-4021586 focused on evaluating the safety, tolerability, and pharmacokinetics of single and multiple doses of the drug in healthy participants.

What are the key findings of the Phase 1 study of CK-4021586?

The study demonstrated that CK-4021586 was safe, well-tolerated, and showed linear pharmacokinetics in healthy participants. Echocardiography was used to evaluate pharmacodynamics.

When is the Phase 2 clinical trial of CK-4021586 expected to begin?

The Phase 2 clinical trial of CK-4021586 in patients with heart failure with preserved ejection fraction (HFpEF) is expected to start in Q4 2024.

What is the potential treatment focus of CK-4021586?

CK-4021586 is focused on potentially treating a subgroup of patients with heart failure with preserved ejection fraction (HFpEF) by addressing underlying hypercontractility.

What are the expectations from the Phase 2 clinical trial of CK-4021586?

The Phase 2 clinical trial is expected to further extend the potential of Cytokinetics' cardiac myosin directed development platform focused on specialty cardiology indications.