Cytokinetics Announces Additional Results From Phase II Trial

Cytokinetics, Inc. recently announced that additional results from COSMIC-HF (Chronic Oral Study of Myosin Activation to Increase Contractility in Heart Failure), a Phase II trial evaluating omecamtiv mecarbil in patients with chronic heart failure, were presented by Tor Biering-Sørensen, MD, PhD, Postdoctoral Research Fellow, Division of Cardiology, Brigham & Women’s Hospital and Harvard Medical School, in a Poster Session at the American College of Cardiology’s 66th Annual Scientific Session (ACC.17) in Washington, DC. The results presented showed that omecamtiv mecarbil improved myocardial deformation, a marker of myocardial function that has been related to outcomes. Omecamtiv mecarbil, a novel investigational cardiac myosin activator that increases cardiac contractility, is being developed by Amgen in collaboration with Cytokinetics for the potential treatment of heart failure.

“These results provide the first, direct echocardiographic evidence in humans that increases in the contractility of cardiac muscle underlie the improvements in overall cardiac function observed in COSMIC-HF,” said Fady I. Malik, MD, PhD, Cytokinetics’ Executive Vice President, Research and Development.

The expansion phase of COSMIC-HF evaluated the pharmacokinetics, pharmacodynamics, safety, and tolerability of oral omecamtiv mecarbil in 448 patients with chronic heart failure and left ventricular systolic dysfunction. Patients were randomized 1:1:1 to receive either placebo or treatment with omecamtiv mecarbil dosed as 25 mg twice daily or 25 mg twice daily with dose escalation to 50 mg twice daily, depending on a plasma concentration of omecamtiv mecarbil after 2 weeks of treatment. The study met its primary pharmacokinetic objective and showed statistically significant improvements in all pre-specified secondary measures of cardiac function in the treatment group receiving pharmacokinetic-based (PK) dose titration.

In this analysis, measures of left ventricular (LV) myocardial deformation, including global circumferential strain (GCS) and mean global longitudinal strain (GLS), were compared at baseline and at 20 weeks of treatment in the placebo group, the 25 mg twice daily group, and the PK-guided dose titration group. At 20 weeks, both mean GLS and GCS improved in the 25 mg twice daily group (p=0.014, p=0.001, respectively), and showed a trend toward improvement in the PK-guided dose titration group (p=0.06, p=0.13, respectively). These results further support that omecamtiv mecarbil directly improves myocardial contractile function.

Omecamtiv mecarbil is a novel cardiac myosin activator. 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 myosin activators are thought 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 cardiac myosin activators increase contractility in the absence of changes in intracellular calcium in cardiac myocytes.

Omecamtiv mecarbil is being developed by Amgen in collaboration with Cytokinetics. Amgen holds an exclusive, worldwide license to omecamtiv mecarbil and related compounds, subject to Cytokinetics’ specified development and commercialization rights. Amgen has also entered an alliance with Servier for exclusive commercialization rights in Europe as well as the Commonwealth of Independent States, including Russia. Servier contributes funding for development and provides strategic support to the program.

Cytokinetics is a late-stage biopharmaceutical company focused on discovering, developing, and commercializing first-in-class muscle activators as potential treatments for debilitating diseases in which muscle performance is compromised and/or declining. As a leader in muscle biology and the mechanics of muscle performance, the company is developing small molecule drug candidates specifically engineered to increase muscle function and contractility. Cytokinetics’ lead drug candidate is tirasemtiv, a fast skeletal troponin activator (FSTA). Tirasemtiv is the subject of VITALITY-ALS, an international Phase III clinical trial in patients with ALS. Tirasemtiv has been granted orphan drug designation and fast track status by the USFDA and orphan medicinal product designation by the European Medicines Agency. Cytokinetics is preparing for the potential commercialization of tirasemtiv in North America and Europe and has granted an option to Astellas Pharma Inc. for development and commercialization in other countries.

Cytokinetics is collaborating with Astellas to develop CK-2127107, a next-generation fast skeletal muscle activator. CK-2127107 is the subject of two ongoing Phase II clinical trials enrolling patients with spinal muscular atrophy and chronic obstructive pulmonary disease.

Cytokinetics is collaborating with Amgen Inc. to develop omecamtiv mecarbil, a novel cardiac muscle activator. Omecamtiv mecarbil is the subject of GALACTIC-HF, an international Phase III clinical trial in patients with heart faiulure. Amgen holds an exclusive worldwide license to develop and commercialize omecamtiv mecarbil with a sublicense held by Servier for commercialization in Europe and certain other countries. Astellas holds an exclusive worldwide license to develop and commercialize CK-2127107. Licenses held by Amgen and Astellas are subject to Cytokinetics’ specified co-development and co-commercialization rights. For more information, visit www.cytokinetics.com.

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