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The number of drugs developed by non-global companies, including biotech start-ups, has increased; however, their characteristics and impact on global regulatory approval are not well understood. Using a public database, we identified new molecular entities (NMEs) approved for hematologic malignancies in the US from January 2011 to December 2022. They were divided into those submitted by non-global companies (non-global group) and those by global companies (global group). We identified 48 NMEs, of which 19 (40%) were classified as non-global. Of these, 13 (68%) were from US-based companies. In the non-global group, 63% (12/19) of the NMEs had received accelerated approval in the US, of which only 50% (6/12) had a post-approval confirmatory trial by September 2023. Regarding the impact on the approval in the European Union (EU) and Japan, the unapproval rate of 2 years after US approval was higher in the non-global group than in the global group in the EU (56% vs. 21%) and Japan (94% vs. 64%). In conclusion, many NMEs from non-global companies had received accelerated approval in the US based on phase I/II trials. NMEs from non-global companies had a higher unapproval rate at 2 years in both the EU and Japan., (© 2024 The Author(s). Clinical Pharmacology & Therapeutics published by Wiley Periodicals LLC on behalf of American Society for Clinical Pharmacology and Therapeutics.)

To further our understanding of the International Council for Harmonization of Technical Requirements for Pharmaceuticals for Human Use (ICH) E17 guideline and promote effective implementation, a public workshop was held in Japan by regulatory agency and industry representatives. In this workshop, important concepts explained in the ICH E17 guideline, such as intrinsic/extrinsic ethnic factors that influence treatment effects ("effect modifiers") and the holistic evaluation of consistency of treatment effect were actively discussed through case studies. The importance of holistic evaluation of consistency was recognized, and it was concluded that the evaluation and relevant discussion should be shared with regulatory authorities, sponsors, and broader stakeholders., (© 2024 The Authors. Clinical Pharmacology & Therapeutics © 2024 American Society for Clinical Pharmacology and Therapeutics.)

We identified the major points that are described in the International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use (ICH) E17 guideline but have not been considered in the past multiregional clinical trials (MRCTs) used for drug approval in Japan to elucidate potential challenges in the implementation of the ICH E17 guideline in Japan. Based on the analysis of 167 MRCTs of 130 drugs, several points, such as the same dose setting and consistency between the overall and Japanese populations, in addition to good clinical practice compliance, have been well considered in ≥ 75% of MRCTs. In contrast, the use of relevant guidelines for disease and primary end point definitions, standardization of efficacy/safety information, sample size allocation, as well as training/validation on subject selection and primary end point, have been addressed less adequately and may need to be considered when planning future MRCTs. This study provides useful information for the implementation of the ICH E17 guideline in Japan., (© 2020 The Authors. Clinical Pharmacology & Therapeutics published by Wiley Periodicals LLC on behalf of American Society for Clinical Pharmacology and Therapeutics.)