New Drug Development Strategy in Japan: Flexibility in Guideline Adherence

Recently, a new type of drug lag, known as “drug loss” has emerged in Japan. It is a condition where the development of a drug approved in other countries has not been initiated in Japan. For 265 new drugs approved in the United States or Europe during 2010–2020, only 31% had commenced development in Japan as of December 31, 2020. A characteristic feature of Japanese guidelines on new drug development is that, in principle, clinical trial data in Japanese participants are required in each study phase. Given key players in new drug development are shifting from large pharmaceutical companies to emerging biopharma companies, primarily based outside Japan, the necessity for Japanese data may contribute to the drug lag. This study aimed to clarify the guideline adherence to new drug applications in Japan. Of the 159 new drugs approved in Japan between April 2019 and March 2024, the clinical data packages for almost all drugs included both pharmacokinetic (PK) data and efficacy and safety data in Japanese participants, irrespective of the study phase or design. We identified three flexible development approaches: the absence of Japanese dose–response data (39.6%), absence of Japanese confirmatory data generated from phase III randomized controlled trials (35.2%), and post‐hoc Japanese PK data (43.0%, 34/79). Biologics, orphan drug designation, antineoplastic agents, and same applicant and originator were identified as factors significantly associated with these flexibilities. The results will help foreign companies, including emerging biopharmas, in formulating effective new drug development strategies, potentially alleviating the drug lag in Japan.