A Comparison of the Pharmacokinetics and Drug Safety Among East Asian Populations

Abstract

Global clinical studies conducted in various countries and regions are increasing. Race and extrinsic ethnic factors are key covariates that may affect the pharmacokinetics (PK), efficacy, and safety of the drug. Genetic similarity among East Asian populations has been confirmed; thus, PK, efficacy, and safety in these populations are expected to be similar, but this has not been confirmed. This study presents a comparison of PK and safety among East Asians from clinical studies sponsored by Pfizer. Four compounds with different characteristics, including mechanism of actions and PK profiles, were selected, and retrospective PK and safety comparisons in East Asians were conducted. No distinct differences were observed in PK and safety across the 4 compounds. These results are consistent with previous reports on PK comparisons and meet the expectations based on genetic similarity among East Asians. Extrapolation of these findings to other compounds should be done with caution, but these results should support the consideration of mutual use of clinical data among East Asian countries.

Toward Optimum Benefit‐Risk and Reduced Access Lag For Cancer Drugs in Asia: A Global Development Framework Guided by Clinical Pharmacology Principles

“…A thorough understanding of regional variations will likely be expected by health authorities (e.g., Pharmaceuticals and Medical Devices Agency) in support of global clinical trial designs and benefit:risk extrapolation not only from the West to Asia but also from the broader Asian region to specific countries and races . Emerging lines of evidence from the genetic, biochemical, and clinical PK levels generally support consistency in clinical pharmacologic characteristics across the Asian races . For example, although the steady‐state exposures of crizotinib are 50% higher in Asian patients compared with non‐Asians, no meaningful differences in exposure or adverse event profile were apparent upon comparison of PK and safety data in Japanese and Korean patients with anaplastic lymphoma kinase‐positive NSCLC .…”

“…13 Emerging lines of evidence from the genetic, biochemical, and clinical PK levels generally support consistency in clinical pharmacologic characteristics across the Asian races. [29][30][31]72,73 For example, although the steady-state exposures of crizotinib are 50% higher in Asian patients compared with non-Asians, 47 no meaningful differences in exposure or adverse event profile were apparent upon comparison of PK and safety data in Japanese and Korean patients with anaplastic lymphoma kinase-positive NSCLC. 31 Therefore, clinical results from different Asian countries are likely to be broadly useful throughout the region.…”

“…[29][30][31]72,73 For example, although the steady-state exposures of crizotinib are 50% higher in Asian patients compared with non-Asians, 47 no meaningful differences in exposure or adverse event profile were apparent upon comparison of PK and safety data in Japanese and Korean patients with anaplastic lymphoma kinase-positive NSCLC. 31 Therefore, clinical results from different Asian countries are likely to be broadly useful throughout the region. Finally, when an exposure-matched regional dosing approach is used in a global phase III trial, it is important to seek feedback from regulatory authorities across regions, with the rationale for the proposed approach described and positioned based on the supporting data.…”

“…In the context of these practical realities, the term “Asia,” as used in this review, refers primarily to the East and North Asian region of the continent (i.e., countries comprised primarily of Chinese, Korean, and Japanese ethnic populations). Indian, Indonesian, and Malay populations, for example, are highly heterogeneous with admixed gene pools and pharmacogenetic characteristics that cannot be assumed to mirror those of the Chinese, Korean, and Japanese populations that are commonly categorized as collectively belonging to the Asian race in the context of drug disposition evaluations and population PK covariate analyses in drug development . Accordingly, although the lack of clinically meaningful ethnic sensitivity in the major Asian ethnicities relative to Western populations may permit seamless consideration and integration of the entire continent as a whole in global drug development, the converse may not be true as differences in drug disposition, PK/PD properties, and consequently dosage requirements between Asian (i.e., Chinese, Korean, and Japanese) and Western populations cannot be assumed to directly apply to other highly heterogeneous sections of Asia, such as the Indian subcontinent, Malaysia, or Indonesia.…”

Population/regional differences in efficacy of 3 drug categories (antidiabetic, respiratory and psychotropic agents) among East Asians: A retrospective study based on multiregional clinical trials

“…Currently, several studies comparing East Asian populations have indicated no large differences in genetic polymorphisms for major drug‐responsive genes . Further, no clinically relevant differences in PK and safety profiles of 4 compounds with different characteristics, based on analysis of global clinical trial data, have been found . Moreover, the percentage rate of MRCTs for drug development from 2008 to 2015 increased to a higher extent in East Asia than in the USA and Europe .…”