薬理ゲノミクスが医療方針に及ぼす影響

Abstract

During the last fifteen years tremendous advances have been made in deciphering the genetic coding of a variety of species from invertebrates, vertebrates and finally man through the formal initiation of the Human Genome Project in October 2000 and its completion in 2003. This information has helped to increase our understanding of how genetics has a pivotal role in the predisposition of many diseased states, the progression of a course of a disease, as well as a patient' s response to a drug, or lack of it. Now in the 21st Century there is a growing trend towards the development of personalized medicine - the right drug for the right individual.

Table of Contents

Executive Summary

• Pharmacogenomics defined
• Application & implementation of PGx by the industry
• Pharmacogenomic strategies, alliances & licensing opportunities
• Pharmacogenomic regulation & implementation
• Reimbursement - coverage, coding & payment
• Future challenges and opportunities

Chapter 1 Pharmacogenomics defined

• Summary
• Introduction
• What is pharmacogenomics & pharmacogenetics?
• Why is pharmacogenomics important?
• Rising R&D costs
• Long development times
• High risk drug development
• Current pharmacogenomic environment
• PGx testing for targeted therapies
• PGx diagnostics to improve safety
• Conclusions

Chapter 2 Implementation of PGx by the industry

• Summary
• Introduction
• Current applications
• Efficacy studies
• Safety and toxicity studies
• Dosing studies
• Implications
• Target identification
• Pre-clinical development
• Clinical development
• Phase 4 development
• Conclusions

Chapter 3 Pharmacogenomic strategies, alliances and licensing opportunities

• Summary
• Introduction
• Pharmaceutical strategies to PGx
• AstraZeneca
• Bayer Schering Pharma
• Eli Lilly
• GlaxoSmithKline
• Pfizer
• Roche
• Conclusions- Pharma PGx strategies
• Biotech strategies to PGx
• Amgen
• Genentech
• Millennium Pharmaceuticals
• Conclusions- Biotech PGx strategies
• Diagnostic strategies to PGx
• Clinical Data
• Dako
• Diaceutics
• Genomic Health
• Genzyme Genetics
• Monogram Biosciences
• Conclusions- Diagnostic PGx strategies
• Interactions between stakeholders
• Consortia
• Intellectual property
• IP conclusions
• Conclusions

Chapter 4 Adoption of pharmacogenomics by regulators

• Summary
• Introduction
• Regulators: US, Europe and Japan
• USA
• Europe
• Japan
• Global PGx harmonization: ICH
• In vitro diagnostics
• The US
• Europe
• PGx guidance on IVD devices
• Conclusions

Chapter 5 PGx and Health Economics

• Summary
• Introduction
• Reimbursement criteria
• Coverage
• Coding
• Payment
• Reimbursement drivers
• Reimbursement in the US
• Reimbursement in Europe
• Eligibility of coverage
• Medical support for PGx coverage
• Dx coding
• Payment and pricing
  • Case study 1: DPD testing
• Cost-effectiveness of PGx
• Commercially viable PGx testing
  • Case Study 2: HLA B*5701 testing
• Industry incentives
• Conclusions

Chapter 6 Future challenges and opportunities

• Summary
• Introduction
• Challenges
• Opportunities
• Market trends
• Market sales
• Conclusions

Chapter 7 Appendix

• Acknowledgements
• Acronyms
• Bibliography
• Glossary
• Index

List of Figures

• Figure 1.1: A genomic timeline
• Figure 1.2: The concept of pharmacogenetics
• Figure 1.3: Costs, time and success rates associated with drug development
• Figure 1.4: R&D costs savings following the application of pharmacogenetics
• Figure 1.5: R&D time savings following the application of genomics technologies in drug discovery
• Figure 2.6: Applications of PGx/biomarkers in drug development timelines
• Figure 2.7: Applications of new technologies to develop new medicines
• Figure 2.8: Response rates to current medicines
• Figure 2.9: Factors affecting efficacy and outcome of drug treatment
• Figure 2.10: Response rates to Iressa
• Figure 2.11: US Reported Adverse Drug Reactions (1995-2001)
• Figure 2.12: Relationship of drugs, disease, genes and gene products
• Figure 2.13: Roche AmpliChip CYP450 array technology
• Figure 2.14: Dose response curves to A) penicillin and B) 6MP
• Figure 2.15: Warfarin mode of action, metabolism and inter-individual variation
• Figure 3.16: Pharmacodynamic biomarkers for dose-selection
• Figure 3.17: PGx and biomarkers to aid decision making
• Figure 3.18: Bayer' s high tech research platform
• Figure 3.19: Obesity patients stratified according drug response and weight loss/weight gain
• Figure 3.20: Pfizer- Applying PGx
• Figure 3.21: Genotyping an integral part of diagnosis and treatment
• Figure 3.22: Roche -Pharmaceuticals' and diagnostics' approach
• Figure 3.23: Amgen - PGx approach in R&D and Drug Therapy
• Figure 3.24: Genentech - development history of Herceptin/HercepTest
• Figure 3.25: Genentech - multiple targeted cancer therapy
• Figure 3.26: Millennium - molecular classifiers of Velcade response
• Figure 3.27: Millennium - Survival classifiers stratifies risk groups
• Figure 3.28: Diaceutics Library - Rationale for its CMR model
• Figure 3.29: Genomic Health Product Pipeline 2008-2009
• Figure 3.30: Genzyme Genetics Product Pipeline 2008-2009
• Figure 3.31: Monogram Biosciences molecular diagnostics approach
• Figure 4.32: The organization of the Interdisciplinary Pharmacogenomic Review Group (IPRG)
• Figure 4.33: FDA' s voluntary PGx submission pathway
• Figure 4.34: The organization of the EMEA
• Figure 5.35: CMS a dominant third-party payor A) 2002A and B) 2008E
• Figure 5.36: Roche - US & EU approval & reimbursement of new tests
• Figure 6.37: Market trends and drivers for the industry
• Figure 6.38: Challenges in PGx
• Figure 6.39: Opportunities in PGx
• Figure 6.40: Key stakeholder in PGx
• Figure 6.41: Future PGx Landscape
• Figure 6.42: Future PGx Landscape
• Figure 6.43: PGx Sales Forecasts 2005-2015

List of Tables

• Table 1.1: PGx - Gene Association Studies
• Table 1.2: Targeted Oncology Products and PGx based tests
• Table 1.3: PGx tests to aide prescription and reduce the risk of ADRs
• Table 2.4: Patient stratification for Herceptin trials
• Table 2.5: Drug withdrawals 1996-2004
• Table 2.6: PharmGKB Knowledge Base annotated PGx genes
• Table 2.7: Warfarin dosage versus genetic variant
• Table 2.8: Disease-associated alleles underlie complex disease phenotypes
• Table 3.9: SNP Coverage per candidate gene
• Table 3.10: Recent strategic alliances and collaborations in PGx
• Table 3.11: PGx driven consortia
• Table 5.12: PGx Dx value based pricing
• Table 5.13: Types of economic evaluations in health care
• Table 5.14: Assessment of the potential cost-effectiveness of PGx interventions
• Table 5.15: Potential cost-effective PGx applications