Evaluation of Characteristics and Ethnic Sensitivity for FDA‐Approved Drugs with Racial and Ethnic Differences in Pharmacokinetics, Safety, and Efficacy

Abstract Racial and ethnic differences in drug disposition and response may have a significant impact on its risk‐benefit balance. Therefore, it is important to examine whether an investigational drug has characteristics that make the pharmacokinetics (PK), safety, and efficacy likely to be affected by intrinsic and extrinsic ethnic factors based on ethnic sensitivity assessment. This assessment is recommended by the latest Japanese guideline (issued in December 2023) for Japanese phase 1 studies before participation in multi‐regional clinical trials (MRCTs). To comprehensively understand characteristics and ethnic sensitivity of drugs that seem to have racial/ethnic differences in its disposition and response, we investigated 620 new molecular entities (NMEs) approved by the United States Food and Drug Administration (FDA) between 2008 and 2023. Of those, only 6.5% (40 NMEs) reported racial/ethnic differences in the PK (5.0%), safety (1.6%), and/or efficacy (0.6%) in the FDA drug labeling, with only one NME (0.16%) having a clinically significant PK difference which requires a reduced starting dose in East Asian patients. Additionally, 4.4% of 620 NMEs reported differences in the pharmacogenetics for drug‐metabolizing enzymes. The comprehensive evaluation of characteristics and ethnic sensitivity of 40 NMEs with racial/ethnic differences in the PK, safety, and/or efficacy indicated two key findings. First, participation in MRCTs from various regions as early as possible is much more important than conduct of an additional phase 1 study in a specific region/country. Second, more attention and deeper evaluation of Asian PK would be needed for drugs with low bioavailability in the overall drug development.