Unique characteristics of regulatory approval and pivotal studies of orphan anticancer drugs in Japan
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The approval of orphan anticancer drugs has increased, with the number exceeding that of non-orphan drugs in Japan in recent years. Although orphan anticancer drugs may have unique characteristics due to their rarity, these have not been fully characterized. We investigated anticancer drugs approved in Japan between April 2004 and November 2017 to reveal the characteristics of regulatory approval and pivotal studies on orphan anticancer drugs compared to non-orphan drugs. The median regulatory review time and number of patients in pivotal studies on orphan anticancer drugs (281.0 days [interquartile range, 263.3–336.0]; 222.5 patients [66.0–454.3]) were significantly lower than those on non-orphan drugs (353.0 days [277.0–535.5]; 521.0 patients [303.5–814.5], respectively) (P < 0.001). Phase II, non-randomized and non-controlled designs were more frequently used in pivotal studies on orphan anticancer drugs (45.9%, 41.9% and 43.2%) than non-orphan drugs (17.2%, 14.1% and 14.1%, respectively). Response rate was more commonly used as a primary endpoint in pivotal studies on orphan anticancer drugs (48.6%) than non-orphan drugs (17.2%). Indications limited by molecular features, second or later treatment line, and accelerated approval in the United States were associated with the use of response rate in orphan anticancer drug studies. In conclusion, we demonstrated that orphan anticancer drugs in Japan have unique characteristics compared to non-orphan drugs: shorter regulatory review and pivotal studies frequently using phase II, non-randomized, or non-controlled designs and response rate as a primary endpoint, with fewer patients.
KeywordsCancer Orphan drug Regulatory approval Pivotal study Endpoint Japan
The authors express gratitude to Katsuya Nakano for his review of the study from a regulatory affairs viewpoint.
Compliance with ethical standards
Conflict of interest
Hiroki Nakayama is an employee of Astellas Pharma Inc. Katsura Tsukamoto declares that he has no conflict of interest. The Global Regulatory Science laboratory is financially maintained by donations from Otsuka Pharmaceuticals Co., Ltd.
This article does not contain any studies with human participants or animals performed by any of the authors.
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