The Necessity of Japanese Clinical Phase 1 Trials Prior to Participation in Multiregional Clinical Trials

In recent years, the so-called "drug loss" issue - in which pharmaceuticals approved in Europe and the United States have not been applied in Japan - has attracted attention. Following the conclusions of the Ministry of Health, Labour and Welfare’s "Study Group on Pharmaceutical Regulations for Strengthening Drug Discovery Capacity and Ensuring Stable Supply," the Ministry has indicated a policy that, from the perspective of ensuring the safety of subjects participating in clinical trials, "in principle, an additional phase 1 study in Japanese is not needed, except in cases where Japanese data are required based on available data regarding safety and tolerability risks." There have been numerous instances in which the pharmacokinetics and safety profiles of Japanese individuals differ significantly from those in Europe and the United States. If Phase III trials are conducted without passing through the safety valve of Phase I trials in Japanese subjects, one cannot help but question whether the safety of Japanese participants can be sufficiently guaranteed. The government has introduced measures to strengthen drug discovery, particularly in Phase I trials. These include revising pharmaceutical regulations in alignment with international harmonization and establishing a globally competitive infrastructure for conducting first-in-human (FIH) trials in Japan. These measures are expected to enhance FIH trial activities and increase their overall number. The necessity of conducting Phase I trials specifically in Japanese populations should be determined scientifically on a case-by-case basis. To facilitate timely drug development, it is essential to make flexible yet scientifically rigorous decisions, ensuring that sufficient data are available to assess risk and safety before initiating Phase III trials in Japan. This paper aims to highlight the necessity of Japanese data in early clinical trials, based on the current discussions surrounding Phase I trial data for Japanese subjects prior to the initiation of multiregional clinical trials.