Amgen (AMGN), Cytokinetics (CYTK) Announce Publication of Significant Omecamtiv Mecarbil Phase 2 Data

December 1, 2016 6:36 AM EST

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Amgen (Nasdaq: AMGN) and Cytokinetics, Inc. (Nasdaq: CYTK) announced The Lancet published results from a Phase 2 clinical trial evaluating omecamtiv mecarbil in patients with chronic heart failure. The COSMIC-HF (Chronic Oral Study of Myosin Activation to Increase Contractility in Heart Failure) trial 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 2015.1

"Data from COSMIC-HF underscore the potential of omecamtiv mecarbil for the treatment of chronic heart failure, a disease that remains a growing healthcare problem worldwide," said John Teerlink, M.D., professor of Clinical Medicine at the University of California, San Francisco and director of Heart Failure at the San Francisco Veterans Affairs Medical Center. "The findings from COSMIC-HF support the therapeutic hypothesis that directly improving cardiac systolic function with a cardiac myosin activator may reverse abnormal structural changes and neurohormonal activation associated with the progression of heart failure."

The trial, which evaluated 448 patients with chronic heart failure and left ventricular systolic dysfunction, showed that dose titration controlled patient exposure to omecamtiv mecarbil. Patients were randomized 1:1:1 to receive either placebo or treatment with omecamtiv mecarbil dosed as 25 mg twice daily or 25 mg with dose escalation to 50 mg twice daily, depending on plasma concentrations of omecamtiv mecarbil after two weeks of treatment.

The pharmacokinetic-based dose titration strategy was designed to maintain patient exposure to omecamtiv mecarbil in the targeted plasma concentration range. Approximately 53 percent of patients in the dose titration group were escalated to a dose of 50 mg twice daily.

Following 20 weeks of treatment, statistically significant improvements were observed in all pre-specified secondary endpoint measures of cardiac function in the dose titration group, compared to placebo. Systolic ejection time increased by 25.0 msec (p<0.0001), stroke volume increased by 3.6 mL (p=0.0217) and heart rate decreased by 3.0 beats per min (p=0.0070). Left ventricular end-systolic and end-diastolic dimensions decreased by 1.8 mm (p=0.0027) and 1.3 mm (p=0.0128), respectively, and were associated with statistically significant reductions in left ventricular end-systolic and end-diastolic volumes. N-terminal pro-brain natriuretic peptide (NT-proBNP) decreased by 970 pg/mL (p=0.0069). In pre-specified exploratory analyses of the dose titration group, placebo-corrected reductions in NT-proBNP persisted four weeks after stopping omecamtiv mecarbil, decreasing further to 1,306 pg/mL (p=0.0006). The data also showed increases in fractional shortening at week 20 compared to placebo in the dose titration group.

"The mechanism of action for omecamtiv mecarbil is novel, and these data reinforce its potential as a new therapy for the millions of patients living with heart failure around the world," said Sean E. Harper, M.D., executive vice president of Research and Development at Amgen. "In collaboration with our partners Cytokinetics and Servier, we look forward to initiating our Phase 3 clinical trial program for omecamtiv mecarbil where we will learn if the improvements in cardiac function observed in the COSMIC-HF study translate into improved cardiovascular outcomes for patients."

"Results from COSMIC-HF provide further validation for the pharmacodynamic effects of omecamtiv mecarbil and show its potential to reverse ventricular enlargement in patients living with chronic heart failure," said Robert I. Blum, president and CEO at Cytokinetics. "We look forward to advancing omecamtiv mecarbil into its Phase 3 program designed to investigate correlations between cardiac function and clinical outcomes."

Adverse events (AEs), including serious AEs, in patients on omecamtiv mecarbil were comparable to placebo. The incidence of adjudicated deaths (3 percent died on placebo, 1 percent died on omecamtiv mecarbil 25 mg twice daily, 2 percent died on omecamtiv mecarbil dose titration), myocardial infarction (1 percent on placebo, 0 percent on omecamtiv mecarbil 25 mg twice daily, 1 percent on omecamtiv mecarbil dose titration) and unstable angina (0 percent on placebo, 1 percent on omecamtiv mecarbil 25 mg twice daily, 0 percent on omecamtiv mecarbil dose titration) was similar. Other cardiac AEs were generally balanced between placebo and active treatment groups. In patients receiving omecamtiv mecarbil compared to placebo, cardiac troponin increased by 0.001 ng/mL and 0.006 ng/mL (median change from baseline at week 20) in the 25 mg twice daily group and dose titration group, respectively. Events of increased troponin (n=278 across all treatment groups) were independently adjudicated and none were adjudicated as an episode of myocardial ischemia or infarction.



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