Regulatory Disparities Between US Accelerated Approval and Japanese Authorization of Oncology Drugs: An Analysis of Evidence Quality

ABSTRACTWhile the accelerated approval (AA) program in the United States expedites the availability of drugs based on preliminary evidence to fulfill unmet medical needs, it has also raised significant concerns, including a lack of robust evidence of efficacy and subsequent withdrawals. Although drug lag and drug loss are growing regulatory concerns in Japan, considering the stricter withdrawal criteria in Japan, careful evaluation of clinical evidence of accelerated approval and approval timing differences is necessary. Here, we aimed to investigate differences in approval timing between the U.S. and Japan, as well as the clinical evidence of accelerated approval drugs that have not yet been approved in Japan. Using the U.S. Food and Drug Administration (FDA) and Japanese Pharmaceuticals and Medical Devices Agency (PMDA) databases, we examined the Japanese and U.S. regulatory status of cancer drugs granted accelerated approval in the U.S. between 2012 and 2022 and the characteristics of evidence for drugs not yet approved in Japan. Of 132 drug‐indication pairs that received accelerated approval between 2012 and 2022, 72 (54.5%) were approved in Japan by June 2024. Of the remaining 60 (45.5%) drugs not yet approved in Japan, the majority had methodological limitations, including a lack of comparators (93.2%) and scarcity of phase III trials (8.5%), as permitted by the accelerated approval program. Our findings suggest the need for an approach that addresses drug lag while ensuring both careful regulatory review and generation of robust evidence for efficacy and safety.