1. Pharmacogenomics in Japan Hiroshi Gushima Scientific Advisor BioFrontier Partners, Inc. and Yamanouchi Pharmaceutical Co., Ltd. October 3, 2002 The 3rd Kitasato University - Harvard School of Public Health Symposium

2. Pharmacogenetics and pharmacogenomics in Japan - 1 l Government Millennium Project n Progress in SNP projects l Pharma SNP Consortium (42 pharmaceutical companies belonging to JPMA) n Frequency of SNPs, Research on expression and function of mutant proteins encoded by SNPs, Database, Immortal cell lines l Creation of Exploratory Clinical Research Center n Tokyo University, Kyoto University, Kurume University and others l Ethics n Basic principles for human genome research (6/2000) n Ethical guidelines for human genome and gene research (4/2001) –Establishment and management of the Ethical Review Board l 141 research organizations (as of August 23, 2002) n Ethical guidelines for epidemiological research (6/2002)

3. Pharmacogenetics and pharmacogenomics in Japan - 2 l PI: Clinical pharmacokinetic studies stratified subjects based on genetic polymorphisms of CYP isozymes are increasing. l PII: Some PII studies are being conducted after the approval by the IRB and/or EC. l PMS: Post-marketing clinical trials of proton pump inhibitors ( Omeprazole, Lansoprazole ) are ongoing. l Activities toward the practical use: n Trastuzumab : IHC and FISH examinations n Imatinib Mesilate, Iressa : prediction of the efficacy by gene expression n Irinotecan : discrimination of adverse reactions by SNP-Invader assays n Interferon : prediction of the efficacy by DNAchip

4. CIOMS The Council for International Organizations of Medical Sciences l Established by WHO and UNESCO in 1949 l Activities : n Bioethics n Health Policy, Ethics and Human Values - An International Dialogue n Drug Development and Use –Safety requirements for the use of drugs –Assessment, monitoring and reporting of adverse drug reactions –Reporting and terminology of adverse drug reactions –Ethical criteria for drug promotion –Surveillance and assessment of drug safety data from clinical trials –Pharmacogenetics and Pharmacoeconomics n International Nomenclature of Diseases

5. CIOMS Working Group on Pharmacogenetics and Pharmacoeconomics l Membership Academia (2), drug regulatory agencies (13) and the pharmaceutical industry (11) n University of Tokyo, MHLW, Yamanouchi l Targets Terminology, impact, cost, regulation, ethics etc. of pharmacogenomics and pharmacogenetics l Working Group Meeting n February 2002, EMEA, London n August 2002, BfArM, Bonn n February 2003, FDA, Washington DC

6. Conditions in Europe and USA l Europe n Report of The Society of Pharmaceutical Medicine’s Working Party on Pharmacogenetics. International Journal of Pharmaceutical Medicine 2001, 15:53 n DIA Workshop on Ethical & Practical Complexities of PGx Research, Basel, Switzerland, 5 March 2002 l USA n Workshop on Pharmacogenetics/Pharmacogenomics in Drug Development and Regulatory Decision-Making, Univ. of Maryland, Rockville Maryland, 16-17 May 2002 –Sponsored by FDA, PhRMA DruSafe and PWG