Reimagining Early-Phase Clinical Development in Japan: From Regulatory Obligation to Global Acceleration.

Japan has faced persistent challenges of "Drug Lag" and "Drug Loss", partly due to the regulatory requirement for Japanese Phase I studies prior to global trial participation. However, recent regulatory reforms have introduced flexibility, creating new opportunities for Japan to strategically contribute to global drug development. This study redefined the value of Japanese Phase I by evaluating three options during the early development phase: the Japanese Phase I waiver, the first-in-human study conducted in Japan, and multifunctional Japanese Phase I studies. We analyzed 12 internal cases of Japanese Phase I waiver consultations and conducted a nationwide survey at early phase clinical trial sites. Our findings highlight Japan's robust clinical trial infrastructure for early phase trials. Japanese clinical trial sites have not only accumulated extensive experience in early phase trials but have also conducted specialized evaluations and enrolled diverse populations (e.g., non-Japanese Asians, Caucasians, and patients). The cycle time analysis showed that trials in Japan could be initiated within globally competitive timelines, often faster than those in the EU. These strengths position Japan as a key location for first-in-human and early phase trials, enabling earlier access to investigational therapies and supporting global development strategies. We propose a flexible, case-by-case approach that leverages Japan's clinical research capabilities. This strategy not only preserves Japan's clinical trial infrastructure but also aligns with national initiatives to strengthen the "Drug-Discovery Ecosystem". By integrating Japan into early phase development, pharmaceutical companies can accelerate global innovation while improving access to Japanese patients.