Cytokinetics Highlights Progress in Cardiac Myosin Modulation Programs and Global Commercial Launch Readiness at Investor & Analyst Day
CYTK 10.16.2024
About Gravity Analytica
NDA for Aficamten Submitted to FDA in Q3
COMET-HF, Confirmatory Phase 3 Clinical Trial of Omecamtiv Mecarbil,and AMBER-HFpEF, Phase 2 Clinical Trial of CK-586, Expected to Begin in Q4
Global Commercial Launch Preparations Underway for FirstPotential Approval Towards
Company Recently Launched Unbranded Disease Awareness Campaign“HCM Beyond The Heart” for Health Care Professionals
“Our pioneering science relating to the mechanics of cardiac muscle function continues to be the engine empowering
COMET-HF: Confirmatory Phase 3 Clinical Trial ofOmecamtiv Mecarbil
Today,
Omecamtiv mecarbilwas previously the subject of GALACTIC-HF, a Phase 3 clinical trial ofomecamtiv mecarbilin over 8,000 patients with heart failure with reduced ejection fraction (HFrEF) which showed a statistically significant risk reduction of heart failure outcomes withomecamtiv mecarbilon top of standard of care. The magnitude of the treatment effect in the pre-specified subgroup of more than 4,000 patients with heart failure with severely reduced ejection fraction (<30%) was observed to be greater than in the overall drug treated population of GALACTIC-HF. The treatment benefit in this subgroup was observed to increase further in patients with recent heart failure hospitalizations, higher NT-proBNP and lower blood pressure. Given the greater observed treatment benefit and high unmet need in the subgroup of patients with HF and severely reduced ejection fraction, the company plans to seek regulatory approval ofomecamtiv mecarbilfor use in this population if the results are confirmed by COMET-HF.
The primary endpoint of COMET-HF is the time to first event in the primary composite endpoint of cardiovascular death, first heart failure event, left ventricular assist device (LVAD) implantation or cardiac transplantation, or stroke. COMET-HF is expected to enroll approximately 1,800 patients randomized on a 1:1 basis to receiveomecamtiv mecarbilor placebo. Patients randomized toomecamtiv mecarbilwill receive up to a maximum dose of 50 mg twice daily based on the plasma concentration ofomecamtiv mecarbilduring a run-in period. Patients will continue to receiveomecamtiv mecarbilor placebo twice daily until approximately 850 primary composite endpoint events have occurred.
AMBER-HFpEF: Phase 2 Clinical Trial of CK-586
Perspectives from Expert Clinicians
Today’s event will feature the following expert clinicians:
Mariko Harper , M.D., MS, FACC,Medical Director, The Hypertrophic Cardiomyopathy Center,Virginia Mason Franciscan Health Shepard D. Weiner , M.D.,Medical Director, Hypertrophic Cardiomyopathy Center and Associate and Professor of Medicine,Columbia University Medical Center G. Michael Felker , M.D., MHS, FACC, FAHA, FHFSA,Professor of Medicine,Division of Cardiology ,Duke Clinical Research Institute , Principal Investigator of COMET-HF, the Confirmatory Phase 3 Clinical Trial ofOmecamtiv Mecarbil
Global Commercial Launch Readiness forAficamten
The Company also will provide updates today relating to earlier commercial readiness activities in
Access to Virtual Event
This event is intended for investor audiences. Interested parties must register online athttps://cytokinetics-2024-analyst-and-investor-day.open-exchange.net/. Registered attendees may access the live virtual event platform by visiting the Investor & Media section of the
AboutAficamten
Aficamtenis an investigational selective, small molecule cardiac myosin inhibitor discovered following an extensive chemical optimization program that was conducted with careful attention to therapeutic index and pharmacokinetic properties and as may translate into next-in-class potential.Aficamtenwas designed to reduce the number of active actin-myosin cross bridges during each cardiac cycle and consequently suppress the myocardial hypercontractility that is associated with hypertrophic cardiomyopathy (HCM). In preclinical models,aficamtenreduced myocardial contractility by binding directly to cardiac myosin at a distinct and selective allosteric binding site, thereby preventing myosin from entering into a force producing state.
The development program foraficamtenis assessing its potential as a treatment that improves exercise capacity and relieves symptoms in patients with HCM as well as its potential long-term effects on cardiac structure and function.Aficamtenwas evaluated in SEQUOIA-HCM (Safety,Efficacy, andQuantitativeUnderstanding ofObstructionImpact ofAficamteninHCM), a positive pivotal Phase 3 clinical trial in patients with symptomatic obstructive hypertrophic cardiomyopathy (HCM).Aficamtenreceived Breakthrough Therapy Designation for the treatment of symptomatic HCM from the
Aficamtenis also currently being evaluated in MAPLE-HCM, a Phase 3 clinical trial ofaficamtenas monotherapy compared to metoprolol as monotherapy in patients with obstructive HCM, ACACIA-HCM, a Phase 3 clinical trial ofaficamtenin patients with non-obstructive HCM, CEDAR-HCM, a clinical trial ofaficamtenin a pediatric population with obstructive HCM, and FOREST-HCM, an open-label extension clinical study ofaficamtenin patients with HCM.
AboutOmecamtiv Mecarbil
Omecamtiv mecarbilis an investigational, selective, small molecule cardiac myosin activator, the first of a novel class of myotropes1designed to directly target the contractile mechanisms of the heart, binding to and recruiting more cardiac myosin heads to interact with actin during systole.Omecamtiv mecarbilis designed to increase the number of active actin-myosin cross bridges during each cardiac cycle and consequently augment the impaired contractility that is associated with heart failure with reduced ejection fraction (HFrEF). Preclinical research has shown thatomecamtiv mecarbilincreases cardiac contractility without increasing intracellular myocyte calcium concentrations or myocardial oxygen consumption.2-4
The development program foromecamtiv mecarbilassessed its potential for the treatment of HFrEF. Positive results from GALACTIC-HF demonstrated a statistically significant effect of treatment withomecamtiv mecarbilto reduce risk of the primary composite endpoint of cardiovascular (CV) death or heart failure events (heart failure hospitalization and other urgent treatment for heart failure) compared to placebo in patients treated with standard of care. Adverse events and treatment discontinuation of study drug were balanced between the treatment arms.
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). CK-586 selectively inhibits the ATPase of intact cardiac myosin but does not inhibit the ATPase of subfragment-1 of myosin (S1) as doesaficamten, a cardiac myosin inhibitor also developed by the Company. Unlikeaficamten, the inhibitory effect of CK-586 requires the presence of the regulatory light chain (RLC) of myosin in the context of the intact myosin dimer (heavy meromyosin or HMM). 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 engineered human HCM heart tissues, CK-586 demonstrated shallow force-concentration response and improved lusitropy.
Lending support for investigating this mechanism of action in HFpEF, a subset of patients with HFpEF resemble patients with non-obstructive hypertrophic cardiomyopathy (HCM) in that those patients have higher ejection fractions, thickened walls of their heart, elevated biomarkers, and symptoms of heart failure. Data from a Phase 2 clinical trial ofaficamtenin patients with non-obstructive HCM show thataficamtenwas well tolerated, improved patient reported outcomes (
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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 properties or potential benefits ofaficamten,omecamtiv mecarbil, CK-586 or any of our other drug candidates, our ability to commence AMBER-HFpEF by the end of 2024, our ability to approval of our new drug application or other marketing authorization application foraficamtenin oHCM or nHCM or commercially launchaficamtenin
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References:
- Psotka MA, Gottlieb SS, Francis GS et al. Cardiac Calcitropes, Myotropes, and Mitotropes.JACC. 2019; 73:2345-53.
- Planelles-Herrero VJ, Hartman JJ, Robert-Paganin J. et al. Mechanistic and structural basis for activation of cardiac myosin force production by omecamtiv mecarbil.
Nat Commun . 2017;8:190. - Shen YT, Malik FI, Zhao X, et al. Improvement of cardiac function by a cardiac myosin activator in conscious dogs with systolic heart failure.Circ Heart Fail. 2010; 3: 522-27.
- Malik FI, Hartman JJ, Elias KA, Morgan BP, Rodriguez H, Brejc K, Anderson RL, Sueoka SH, Lee KH, Finer JT, Sakowicz R. Cardiac myosin activation: a potential therapeutic approach for systolic heart failure.Science. 2011 Mar 18;331(6023):1439-43.
Source: Cytokinetics, Incorporated