Heart Defect

November 30, 2015

Amgen and Cytokinetics have reported results of a phase II trial evaluating omecamtiv mecarbil in patients with chronic heart failure. COSMIC-HF was a double-blind, randomized, placebo-controlled, multicenter trial. The trial consisted of two parts, a dose escalation phase and a larger and longer expansion phase. In the dose escalation phase, 96 patients were randomized 1:1:1:1 to placebo or one of three omecamtiv mecarbil oral modified-release formulations in two cohorts (25mg twice daily or 50mg twice daily). Each patient cohort was followed for 35 days. The expansion phase evaluated 448 chronic heart failure patients with reduced ejection fraction who were dosed with the selected oral formulation of omecamtiv mecarbil for 20 weeks and followed for a total of 24 weeks. Patients were randomized 1:1:1 to receive either placebo or treatment with omecamtiv mecarbil 25mg twice daily or 25mg with dose escalation to 50mg twice daily depending on plasma concentrations of omecamtiv mecarbil after two weeks of treatment. Following 20 weeks of treatment, statistically significant improvements were observed in pre-specified secondary endpoint measures of cardiac function in the dose titration group, compared to placebo. Systolic ejection time increased by 25 msec (p<0.001), stroke volume increased by 3.63mL (p=0.022) and heart rate decreased by 2.97 beats per min (p=0.007). Left ventricular end-systolic and end-diastolic dimensions decreased by 1.79mm (p=0.003) and 1.29mm (p=0.013), 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 970pg/mL (p=0.007).