title: Ethnic sensitivity assessment - pharmacokinetic comparability between Japanese and non-Japanese healthy subjects on selected mAbs.
abstract: OBJECTIVE
  Ethnic sensitivity studies (ESSs), where safety and pharmacokinetics (PK) are assessed in Japanese subjects, are routinely conducted according to Japanese regulatory requirement before the subsequent clinical studies. The necessity of ESSs is questionable in case of mAbs, where inherent IgG characteristics are considered ethnically insensitive. This report investigated PK profiles and immunogenicity (IG) following a single administration of mAbs in Japanese and non-Japanese healthy subjects.
  
  
  METHODS
  PK and IG comparison between Japanese and non-Japanese healthy subjects was made on mAbs data available from public domain and unpublished internal reports. PK comparison was made based on statistical approach as well as assumed typical IgG profile using modeling and simulation.
  
  
  RESULTS
  When compared directly, most mAbs showed no difference between ethnic groups. When profiles of various mAbs were fit to an assumed typical IgG PK model, the majority of mAbs follow the expected behavior regardless of ethnicities. Deviations from this behavior did not appear to be due to inherent ethnic differences. When the incidence of IG was assessed, only Adalimumab showed apparent ethnic difference.
  
  
  CONCLUSIONS
  The overall lack of observational difference may facilitate discussion of mAbs' early clinical development in Japan, including the utility of dedicated ESSs.
authors.affiliation: Novartis Pharma K.K. , 4-17-30 Nishi-Azabu, Minato-ku, Tokyo 106-8618 , Japan +81 3 3797 5354 ; +81 3 3797 5467 ; soichiro.matsushima@novartis.com.
authors.forename: Soichiro
authors.initials: S
authors.lastname: Matsushima
authors.forename: Yue
authors.initials: Y
authors.lastname: Huang
authors.forename: Hikoe
authors.initials: H
authors.lastname: Suzuki
authors.forename: Junichi
authors.initials: J
authors.lastname: Nishino
authors.forename: Peter
authors.initials: P
authors.lastname: Lloyd
mesh_terms: D000911:Antibodies, Monoclonal / Q000276:immunology / Q000493:pharmacokinetics*; D044466:Asian People; D003198:Computer Simulation; D003627:Data Interpretation, Statistical; D006801:Humans; D007074:Immunoglobulin G / Q000276:immunology*; D007564:Japan; D008954:Models, Biological
chemical_list: D000911:Antibodies, Monoclonal; D007074:Immunoglobulin G
keywords: Japan; ethnic sensitivity; immunogenicity; mAb; pharmacokinetics