T-35: Considerations in Using Biomarkers as Efficacy Endpoints: The Review of Clinical Trials of Orphan Drugs Approved in Japan

Poster Presenter

Tomoko Nakai Minamiguchi

Reviewer
Pharmaceuticals and Medical Devices Agency (PMDA)
Japan

Objectives

Our study’s purpose was to identify important points for using a biomarker as an efficacy endpoint based on the review reports of orphan drugs approved in Japan.

Method

From the list provided by NIBIOHN and the package inserts, we searched orphan drugs approved from January 2008 to March 2018 in which biomarkers were used for efficacy evaluation. We analyzed descriptions about an efficacy evaluation based on biomarkers from their review reports.

Results

We identified 174 orphan drugs for treatment of disease approved in Japan. Of these 174 drugs, a total of 81 drugs were excluded because 22 drugs of those drugs did not have Japanese subjects’ data in their pivotal clinical trials described in package inserts and 59 drugs of those drugs were oncology drugs which were assumed to have been assessed their efficacy in unique manners. Biomarkers were used as efficacy endpoints in 56 out of the 93 that remained. Therefore, we reviewed 56 drug’s review reports. Our review of the description about the appropriateness of biomarkers revealed that the sponsor’s explanation and PMDA’s discussion consisted of the relationship between biomarkers and clinical outcome, the utilization of biomarkers in clinical guidelines and the experience of using biomarkers as endpoints in other clinical trials. Some biomarkers which were clearly related to treatment target sometimes were not discussed about the appropriateness in the review reports. The analysis of clinical outcome data utilization other than biomarker revealed that these clinical outcome data obtained from secondary endpoints or other clinical studies were also evaluated to support efficacy. In some cases, especially when the efficacy of drugs was evaluated only in biomarkers in clinical trials, evaluation of clinical outcome was required in post-marketing study. Efficacy of some drugs was evaluated by composite endpoints including biomarkers and clinical outcome assessments.

Conclusion

Our study identified important points to use biomarkers as efficacy endpoints, such as the relationship with clinical outcome, the utilization in clinical guidelines, and the experience of utilization as endpoints. Moreover, it is also important to evaluate clinical outcome data obtained from secondary endpoints or other clinical studies in addition to biomarker data. The cases and points we identified in this study will be useful to assess the appropriateness of the utilization of biomarkers in future orphan drug development.