Verifying Clinical Benefit of New Anticancer Drugs After Regulatory Approval Based on Exploratory Studies.

Abstract

Background: In Japan, anticancer drugs are often approved based on the objective response rate (ORR) when the conduct of a confirmatory study is difficult or expected to take a considerably long time. However, it remains unclear how frequently post-marketing confirmatory studies are conducted and for which indications they are implemented. We aimed to understand the status of post-marketing confirmatory studies for anticancer drugs approved based on ORR.

Methods: We investigated the status of post-marketing confirmatory studies on anticancer drug indications approved based on ORR in Japan between 2015 and 2022. In addition, we compared the status of post-marketing requirements and subsequent regulatory actions between Japan and the US for the indications commonly approved in both countries.

Results: We found that 60% of the indications did not have planned confirmatory studies, with many receiving orphan drug designations. This observation is consistent with the Japanese regulations that allow the approval of anticancer drugs based on ORR, for which confirmatory studies are difficult to conduct or expected to take a long time. Indications received conditional approval in Japan were fewer compared to those received accelerated approval in the US, and post-marketing confirmatory studies were less frequently requested from the regulatory authority in Japan. Although the results of post-marketing confirmatory studies were often utilized in regulatory actions in Japan (including modifications to approved indications), no indications were found where these results led to withdrawal of approval or additional confirmatory study requirements, and the evaluations of the results were not disclosed when they did not lead to regulatory actions.

Conclusions: To facilitate smoother regulatory actions based on the results of post-marketing confirmatory studies, it would be beneficial to require the submission of the results of post-marketing confirmatory studies if it is feasible following the approval based on ORR.