Ito Akira, Narukawa Mamoru
Department of Clinical Medicine (Pharmaceutical Medicine), Graduate School of Pharmaceutical Sciences, Kitasato University, 5-9-1, Shirokane, Minato-Ku, Tokyo, Japan.
Daiichi Sankyo, Inc, Basking Ridge, NJ, USA.
Ther Innov Regul Sci. 2025 May;59(3):542-548. doi: 10.1007/s43441-025-00757-3. Epub 2025 Feb 10.
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.
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.
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.
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.
在日本，当确证性研究难以开展或预计耗时很长时，抗癌药物通常根据客观缓解率（ORR）获得批准。然而，目前尚不清楚上市后确证性研究的开展频率以及针对哪些适应症开展此类研究。我们旨在了解基于ORR获批的抗癌药物的上市后确证性研究情况。
我们调查了2015年至2022年期间日本基于ORR获批的抗癌药物适应症的上市后确证性研究情况。此外，我们比较了日本和美国在两国共同获批适应症方面的上市后要求及后续监管行动情况。
我们发现60%的适应症没有计划开展确证性研究，其中许多获得了孤儿药认定。这一观察结果与日本允许基于ORR批准抗癌药物的法规一致，对于此类药物，确证性研究难以开展或预计耗时很长。与在美国获得加速批准的适应症相比，在日本获得有条件批准的适应症较少，并且日本监管机构对上市后确证性研究的要求也较少。尽管上市后确证性研究的结果在日本的监管行动中经常被采用（包括对获批适应症的修改），但未发现这些结果导致批准撤销或额外确证性研究要求的适应症，并且当结果未导致监管行动时，其评估结果未被披露。
为了便于基于上市后确证性研究结果进行更顺畅的监管行动，如果在基于ORR批准后可行的话，要求提交上市后确证性研究结果将是有益的。
