Phase III GALACTIC-HF trial of AMG 423 meets primary endpoints but not secodnary ones in heart failure.- Cytokinetics

Cytokinetics announced the primary results from GALACTIC-HF (Global Approach to Lowering Adverse Cardiac Outcomes Through Improving Contractility in Heart Failure), the Phase III event-driven cardiovascular outcomes clinical trial of AMG 423 (omecamtiv mecarbil). GALACTIC-HF, one of the largest Phase III global cardiovascular outcomes trials in heart failure ever conducted, enrolled 8,256 patients who were at risk of hospitalization and death, despite being well treated on standard of care therapy. The statistically significant reduction in the composite of heart failure events or cardiovascular deaths, without significant imbalances in the overall incidence of adverse events across treatment arms, was observed in one of the broadest and most diverse range of patients enrolled in a contemporary heart failure trial. GALACTIC-HF included both inpatients and outpatients, and with a high representation of participants with moderate to severe heart failure symptoms as well as lower ejection fraction, systolic blood pressure and renal function. No reduction in the secondary endpoint of time to CV death was observed. Death from cardiovascular causes occurred in 808 (19.6%) patients treated with omecamtiv mecarbil and 798 patients (19.4%) assigned to placebo (hazard ratio, 1.01; 95% CI, 0.92 to 1.11; p=0.86). The pre-specified analysis of change from baseline to week 24 in the KCCQ total symptom score by randomization setting (inpatient mean difference [95% CI]: 2.50 [0.54, 4.46], outpatient mean difference: -0.46 [-1.40, 0.48], joint P = 0.028) did not meet the significance threshold of P=0.002 based upon the multiplicity control testing procedure. No other secondary endpoints were met in accordance with the prespecified statistical analysis. The effect of omecamtiv mecarbil was consistent across most prespecified subgroups and with a potentially greater treatment effect suggested in patients with a lower left ventricular ejection fraction (LVEF less than 28%, n=>4,000, hazard ratio, 0.84; 95% CI 0.77, 0.92; interaction p=0.003). Omecamtiv mecarbil also significantly decreased NT-proBNP concentrations by 10% (95% CI 6-14%) at Week 24 compared to placebo. The results were presented by John Teerlink, M.D., Professor of Medicine, University of California San Francisco, Director of Heart Failure, San Francisco Veterans Affairs Medical Center and Executive Committee Chair, GALACTIC-HF, in a Late Breaking Clinical Trial session at the American Heart Association (AHA) Scientific Sessions 2020, and were simultaneously published in the New England Journal of Medicine.See: "Cardiac Myosin Activation with Omecamtiv Mecarbil in Systolic Heart Failure." John R. Teerlink et al. NEJM November 13, 2020 DOI: 10.1056/NEJMoa2025797