Commencement of Next Stage in International Phase II Clinical Trial of Oral Formulation of Omecamtiv Mecarbil in Patients with Heart Failure
South San Francisco, CA - March 28, 2014
Cytokinetics, Incorporated (Nasdaq: CYTK) announced today that the expansion phase of the COSMIC-HF (Chronic Oral Study of Myosin Activation to Increase Contractility in Heart Failure) has opened to enrollment. COSMIC-HF is a Phase II double-blind, randomized, placebo-controlled, multicenter clinical trial designed to assess the pharmacokinetics and tolerability of omecamtiv mecarbil dosing orally in patients with heart failure and left ventricular systolic dysfunction. The expansion phase of COSMIC-HF will enroll approximately 450 patients randomized 1:1:1 to receive placebo, 25 mg, or 50 mg twice daily of omecamtiv mecarbil. Escalation to the 50 mg dose will depend on the plasma concentration of omecamtiv mecarbil following 2 weeks of oral dosing at 25 mg twice daily.
The primary objective of the expansion phase of this trial is to characterize the safety, tolerability, and pharmacokinetics of omecamtiv mecarbil dosed orally during 20 weeks of treatment. The secondary objectives are to assess the changes from baseline in systolic ejection time, stroke volume, left ventricular end-systolic diameter, left ventricular end-diastolic diameter, heart rate and N-terminal pro-brain natriuretic peptide (a biomarker associated with the severity of heart failure) during 20 weeks of treatment. The expansion phase of COSMIC-HF is expected to enroll heart failure patients from approximately 100 clinical sites internationally.
COSMIC-HF is being conducted by Amgen in collaboration with Cytokinetics. Amgen holds an exclusive, worldwide license to develop and commercialize omecamtiv mecarbil and related compounds, subject to Cytokinetics' specified development and commercialization participation rights.
"The opening to enrollment of the expansion phase of COSMIC-HF is an important step forward in the evaluation of a plasma concentration-guided dose titration strategy for omecamtiv mecarbil in patients with heart failure" stated Andrew A. Wolff, MD, FACC, Cytokinetics' Senior Vice President of Clinical Research and Development and Chief Medical Officer. "This international clinical trial has the potential to inform further clinical development strategies for omecamtiv mecarbil."
Background on COSMIC-HF
Cytokinetics and Amgen selected an oral formulation of omecamtiv mecarbil for the expansion phase of COSMIC-HF based on the results of the completed dose escalation phase of COSMIC-HF. The dose escalation phase of COSMIC-HF was designed to assess the pharmacokinetics and tolerability of three oral modified-release formulations of omecamtiv mecarbil in patients with heart failure and left ventricular systolic dysfunction. During the dose escalation phase, approximately 40 patients were randomized 1:1:1:1 to placebo or one of three different oral formulations of omecamtiv mecarbil in each of two ascending dose escalation cohorts to enable selection of one of these oral formulations for the expansion phase of the trial. The dose of omecamtiv mecarbil was 25 mg twice daily in the first dose escalation cohort and 50 mg twice daily in the second dose escalation cohort. Additional information about COSMIC-HF can be found at www.clinicaltrials.gov.
About Omecamtiv Mecarbil
Omecamtiv mecarbil is a novel cardiac myosin activator and is the subject of a collaboration between Cytokinetics and Amgen. Cardiac myosin is the cytoskeletal motor protein in the cardiac muscle cell that is directly responsible for converting chemical energy into the mechanical force resulting in cardiac contraction. Cardiac contractility is driven by the cardiac sarcomere, a highly ordered cytoskeletal structure composed of cardiac myosin, actin and a set of regulatory proteins, which is the fundamental unit of muscle contraction in the heart. Cardiac myosin activators have been shown preclinically to work in the absence of changes in intracellular calcium in cardiac myocytes by a novel mechanism that directly stimulates the activity of the cardiac myosin motor protein. Cardiac myosin activators appear to accelerate the rate-limiting step of the myosin enzymatic cycle and shift the enzymatic cycle in favor of the force-producing state. Preclinical research has shown that this mechanism does not increase the velocity of cardiac contraction, but instead, increases the systolic ejection time, resulting in an increase in cardiac contractility and cardiac function in a potentially more oxygen-efficient manner.
Cytokinetics is a clinical-stage biopharmaceutical company focused on the discovery and development of novel small molecule therapeutics that modulate muscle function for the potential treatment of serious diseases and medical conditions. Cytokinetics' lead drug candidate from its cardiac muscle contractility program, omecamtiv mecarbil, is in Phase II clinical development for the potential treatment of heart failure. Amgen Inc. holds an exclusive license worldwide to develop and commercialize omecamtiv mecarbil and related compounds, subject to Cytokinetics' specified development and commercialization participation rights. Cytokinetics is independently developing tirasemtiv, a fast skeletal muscle activator, as a potential treatment for diseases and medical conditions associated with neuromuscular dysfunction. Tirasemtiv is currently the subject of a Phase II clinical trials program and has been granted orphan drug designation and fast track status by the U.S. Food and Drug Administration and orphan medicinal product designation by the European Medicines Agency for the potential treatment of amyotrophic lateral sclerosis (ALS). Cytokinetics is collaborating with Astellas Pharma Inc. to develop CK-2127107, a skeletal muscle activator structurally distinct from tirasemtiv, for non-neuromuscular indications. All of these drug candidates have arisen from Cytokinetics' muscle biology focused research activities and are directed towards the cytoskeleton. The cytoskeleton is a complex biological infrastructure that plays a fundamental role within every human cell. Additional information about Cytokinetics can be obtained at www.cytokinetics.com.
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