Pharmacogenomics in Japan

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

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

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

4. CIOMS The Council for International Organizations of Medical Sciences • Established by WHO and UNESCO in 1949 • Activities : • Bioethics • Health Policy, Ethics and Human Values - An International Dialogue • 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 • International Nomenclature of Diseases

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

6. Conditions in Europe and USA • Europe • Report of The Society of Pharmaceutical Medicine’s Working Party on Pharmacogenetics. International Journal of Pharmaceutical Medicine 2001, 15:53 • DIA Workshop on Ethical & Practical Complexities of PGx Research, Basel, Switzerland, 5 March 2002 • USA • 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