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

ABSTRACT

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.