Lack of Differences in the Pharmacokinetics of Therapeutic Monoclonal Antibodies Between Japanese and Non‐Japanese Individuals

Evaluation of the pharmacokinetics (PK) of new drugs in Japanese individuals is regularly requested by the Japanese regulatory agency prior to participation in global clinical trials or for bridging approaches for regulatory approval. However, the need for PK assessments in the Japanese population may be less compelling for monoclonal antibodies (mAbs) compared to other drugs, given that the intrinsic properties of immunoglobulin G molecules are generally considered ethnically insensitive. This prompted an evaluation of the currently available evidence for potential PK differences for mAbs between Japanese and Non-Japanese populations. We reviewed 137 mAbs approved in the United States, of which 101 were also approved in Japan, to evaluate whether PK differences between Japanese and non-Japanese individuals have been reported. PK was found to be similar between Japanese and non-Japanese, predominantly Caucasians/Whites, for 59 out of 101 mAbs. Although PK differences were identified for 26 out of 101 mAbs approved in Japan, these differences were largely attributed to body weight differences between Japanese and non-Japanese populations. After adjusting for these body weight differences, most mAbs demonstrated no meaningful PK differences across the ethnic groups. Importantly, the observed differences were reported not to translate into clinically meaningful impact on pharmacodynamics, safety, and efficacy to warrant different dosing recommendations. No differences in dosing recommendations could be detected for any of the 101 mAbs approved in Japan compared to the United States. Overall, these data suggest a lack of a convincing scientific rationale for the necessity of dedicated PK studies in Japanese versus non-Japanese individuals for mAbs.