title: Use of Pharmacogenomics and Biomarkers in the Development of New Drugs for Alzheimer Disease in Japan.
abstract: OBJECTIVE
  Pharmacogenomics (PGx) and biomarkers have been utilized for improving the benefit/risk ratios of drugs and the efficiency of drug development. In the development of drugs for Alzheimer disease (AD), a number of clinical trials have failed to demonstrate clinical efficacy. To overcome this circumstance, the importance of using PGx/biomarkers for enhancing recruitment into clinical trials and for evaluating the efficacy of treatments has been increasingly recognized. In this article, the current status and examples of the use of PGx/biomarkers in Japan for drug development are explained.
  
  
  METHODS
  Guidelines, notifications, and administrative notices related to PGx/biomarkers were downloaded from the Web sites of the Pharmaceuticals and Medical Devices Agency (PMDA), the US Food and Drug Administration, and the European Medicines Agency. Data from clinical studies of AD drugs were obtained from the review reports of the PMDA. To analyze the current status of the use of PGx/biomarkers in Japan, "Issues to Consider in the Clinical Evaluation and Development of Drugs for Alzheimer's Disease (Interim Summary)" was also downloaded from PMDA Web site.
  
  
  RESULTS
  There are 2 major measures of utilizing PGx/biomarkers for drug development: (1) biomarker qualification and (2) companion diagnostics. Recently, the PMDA issued a number of guidelines and notifications for their practical use. Although examples of qualified PGx/biomarkers and approved companion diagnostics are limited at present, it is expected that the use of PGx/biomarkers for the development of drugs against AD would increase.
  
  
  CONCLUSIONS
  For promoting the use of PGx/biomarkers in the development of drugs against AD, PGx/biomarkers should be qualified as early as possible. To that end, accumulating data on PGx/biomarkers from nonclinical or clinical trials and the concurrent development of reliable diagnostics in the early stage of the development process are indispensable. It is important to strengthen collaboration among the academia, industries, and regulatory agencies, followed by the establishment of an effective guideline in the area of AD.
authors.affiliation: Division of Medical Economics, Bureau of Health Insurance, Ministry of Health, Labor, and Welfare, Tokyo, Japan. Electronic address: ootsubo-yasuto@mhlw.go.jp.
authors.forename: Yasuto
authors.initials: Y
authors.lastname: Otsubo
mesh_terms: D000544:Alzheimer Disease / Q000097:blood / Q000188:drug therapy*; D054316:Biomarkers, Pharmacological / Q000097:blood*; D002986:Clinical Trials as Topic; D017277:Drug Approval; D006801:Humans; D007564:Japan; D018697:Nootropic Agents / Q000493:pharmacokinetics / Q000627:therapeutic use*; D010597:Pharmacogenetics
chemical_list: D054316:Biomarkers, Pharmacological; D018697:Nootropic Agents
keywords: Alzheimer disease; Japan; biomarkers; pharmacogenomics