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.

Research design and 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IG comparison between Japanese and non-Japanese healthy subjects was made on mAbs data available from public domain and unpublished internal reports.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.

Keywords:

• ethnic sensitivity
• immunogenicity
• Japan
• mAb
• pharmacokinetics

Acknowledgements

All authors were involved in the data analysis, the development and writing of the manuscript.

Declaration of interest

This paper has been supported by Novartis Pharma. S Matsushima, Y Huang, H Suzuki, and J Nishino are all employees of Novartis Pharma group. P Lloyd was an employee of Novartis Pharma group during the development of the manuscript. The authors declared no potential conflicts of interest with respect to the research, authorship and/or publication of the manuscript apart from those disclosed.

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