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

Clin Pharmacol Drug Dev. 2019 Aug;8(6):702-712. doi: 10.1002/cpdd.617. Epub 2018 Sep 19.


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.

Keywords: bioavailability; drug product bridging strategy; emicizumab; hemophilia A; monoclonal antibody.

Publication types

  • Comparative Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Antibodies, Bispecific / administration & dosage*
  • Antibodies, Bispecific / pharmacokinetics*
  • Antibodies, Monoclonal, Humanized / administration & dosage*
  • Antibodies, Monoclonal, Humanized / pharmacokinetics*
  • Biological Availability
  • Drug Compounding
  • Healthy Volunteers
  • Humans
  • Injection Site Reaction
  • Injections, Subcutaneous
  • Japan
  • Male
  • Young Adult


  • Antibodies, Bispecific
  • Antibodies, Monoclonal, Humanized
  • emicizumab