OREANDA-NEWS. Cytokinetics, Inc. (Nasdaq:CYTK) today announced that additional results from COSMIC-HF (Chronic Oral Study of Myosin Activation to Increase Contractility in Heart Failure), a Phase 2 trial evaluating omecamtiv mecarbil in patients with chronic heart failure, were presented in a Rapid Fire Abstract Session at the 20th Annual Heart Failure Society of America Scientific Meeting in Orlando, FL. The results presented show that omecamtiv mecarbil may improve symptoms in patients with moderate to severe heart failure symptoms versus placebo after 20 weeks of double-blind treatment, as measured by the Kansas City Cardiomyopathy Questionnaire (KCCQ) Total Symptom Score (TSS), one of the sub-domains of a self-administered questionnaire that measures quality-of-life in patients with heart failure. 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.

“It’s encouraging to see in these data that patients’ self-reported heart failure symptoms may have improved in association with improvements in cardiac function in those receiving omecamtiv mecarbil versus placebo,” said Fady I. Malik, MD, PhD, Cytokinetics' Executive Vice President, Research and Development. “We look forward to further investigating how these potential improvements may translate to clinical outcomes in our planned Phase 3 clinical trial to be conducted in collaboration with Amgen.

COSMIC-HF: Expansion Phase Design and Results  

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 two 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 dose titration. The results were initially presented as a Late-Breaking Clinical Trial at the American Heart Association (AHA) Scientific Sessions 2015. Additional results were also presented at Heart Failure 2016, the annual congress of the Heart Failure Association of the European Society of Cardiology, in May 2016, showing that omecamtiv mecarbil improved left ventricular (LV) systolic function, LV end-diastolic volume and NT-proBNP over time, suggesting potentially favorable ventricular remodeling and progressive reduction in myocardial wall stress.

The KCCQ TSS data from COSMIC-HF are shown in the table below. At week 20, the KCCQ TSS was increased (with increases in the score reflecting improvement) in a dose-related fashion, with a 4.9 point improvement in the PK-guided dose titration group (p=0.03). This improvement was greater among patients who were moderately to severely symptomatic at baseline, with the largest magnitude in the PK-guided dose titration treatment group (6.5, p=0.09). Patients who were asymptomatic or mildly symptomatic had modest improvements in the TSS.

  Placebo  OM 25 mg po BID   OM PK-Titration 
TSS-Overall (n) 149 150 146
Baseline - Mean (SD)  69.7 (21.2)  70.9 (22.0) 67.3 (21.3)
Change from baseline at Week 20 - Mean (SD) 5.0 (1.6) 6.6 (1.6) 9.9 (1.6)
Difference vs. Placebo - Mean (95%CI) --- 1.7 (-2.8, 6.1) 4.9 (0.5, 9.4)**
TSS-Group 1: Asymptomatic to Mildly Sx (n) 81 86 75
Baseline - Mean (SD) 77.3 (16.4) 80.2 (18.3) 78.4 (17.4)
Change from baseline at Week 20 - Mean (SD) 1.6 (1.8) 2.7 (2.0) 4.3 (1.6)
Difference vs. Placebo - Mean (95%CI) --- 1.2 (-4.1, 6.4) 2.7 (-2.2, 7.6)
TSS-Group 2: Moderately to Very Severely Sx (n)   67 64 71
Baseline - Mean (SD) 60.2 (22.6) 58.3 (20.2) 55.5 (18.7)
Change from baseline at Week 20 - Mean (SD) 9.5 (2.7) 11.3 (2.6) 16.0 (2.7)
Difference vs. Placebo - Mean (95%CI) --- 1.8 (-5.7, 9.3) 6.5 (-1.0, 14.0)*
(*p<0.10; **p<0.05)

About Heart Failure

Heart failure is a grievous condition that affects more than 23 million people worldwide, about half of whom have reduced left ventricular function. It is the leading cause of hospitalization and readmission in people age 65 and older. Despite broad use of standard treatments and advances in care, the prognosis for patients with heart failure is poor. An estimated one in five people over the age of 40 are at risk of developing heart failure, and approximately 50 percent of people diagnosed with heart failure will die within five years of initial hospitalization.

About Omecamtiv Mecarbil

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 granted a sublicense to Servier to commercialize omecamtiv mecarbil in Europe, as well as the Commonwealth of Independent States, including Russia.

About Cytokinetics

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 muscle troponin activator, for the potential treatment of ALS. Tirasemtiv 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 ALS. Cytokinetics retains the right to develop and commercialize tirasemtiv, subject to an option held by Astellas Pharma Inc. Cytokinetics is also collaborating with Astellas to develop CK-2127107, a fast skeletal muscle activator, for the potential treatment of spinal muscular atrophy, chronic obstructive pulmonary disease and ALS. Cytokinetics is collaborating with Amgen Inc. to develop omecamtiv mecarbil, a novel cardiac muscle activator, for the potential treatment of heart failure. Amgen holds an exclusive license worldwide to develop and commercialize omecamtiv mecarbil and Astellas holds an exclusive license worldwide to develop and commercialize CK-2127107. Both licenses are subject to Cytokinetics' specified development and commercialization participation rights.