Relative and Absolute Bioavailability Study of Emicizumab to Bridge Drug Products and Subcutaneous Injection Sites in Healthy Volunteers

Emicizumab (ACE910) is a bispecific antibody that is a novel, subcutaneously injectable treatment for patients with hemophilia A. This study assessed the relative bioavailability of emicizumab between old and new drug products (DPs) and among 3 commonly used subcutaneous injection sites (abdomen, upper arm, and thigh), together with its absolute bioavailability in healthy volunteers. Forty‐eight healthy volunteers were randomized into 4 groups to receive a single subcutaneous injection of 1 mg/kg with the old or new DP, and another 12 volunteers each received a single, 90‐minute, intravenous infusion of 0.25 mg/kg with the new DP. Similar pharmacokinetic profiles were observed between the DPs, with geometric mean ratios of 1.199 (90% confidence interval [CI] 1.060‐1.355) for the maximum plasma concentration and 1.083 (90% CI 0.920‐1.275) for area under the plasma concentration‐time curve extrapolated to infinity. The geometric mean ratios of maximum plasma concentration and area under the plasma concentration‐time curve extrapolated to infinity for upper arm versus abdomen were 0.823 (90% CI 0.718‐0.943) and 0.926 (90% CI 0.814‐1.053), respectively, and those for thigh versus abdomen were 1.168 (90% CI 1.030‐1.324) and 1.073 (90% CI 0.969‐1.189), respectively. Absolute bioavailability ranged from 80.4% to 93.1%. These results suggested that no emicizumab dose adjustment would be needed when switching the DPs or injecting to different sites interchangeably and that emicizumab injected subcutaneously is highly bioavailable.