Pharmacogenomics for Clinical Use and in Drug Development

Content

• 1. Overview
  • 1.1 Statement of Report
  • 1.2 Objectives of this Report
  • 1.3 Scope of the Study
  • 1.4 Methodology
  • 1.5 Executive Summary
• 2. Introduction
  • 2.1 Pharmacogenomic Testing Overview
    • 2.1.1 Clinical Applications
    • 2.1.2 Technologies for Pharmacogenomic Diagnostic Tools
    • 2.1.3 Drug and Diagnostic Combinations
    • 2.1.4 Economic Impact of Healthcare Costs
  • 2.2 Genetic Variation among Individuals
    • 2.2.1 Population Genomics
    • 2.2.2 SNPs and Haplotypes
    • 2.2.3 HapMap
      • 2.2.3.1 The International HapMap Project
      • 2.2.3.2 HapMap Participants and Funding Sources
  • 2.3 Drug Metabolism
    • 2.3.1 Adverse Drug Reactions (ADRs)
    • 2.3.2 Drug-Test Combinations
  • 2.4 Impact of Pharmacogenomics
    • 2.4.1 How Will Gene Variation Be Used in Predicting Drug Response?
    • 2.4.2 How Will Drug Development and Testing Benefit from Pharmacogenomics?
    • 2.4.3 Advantages of Pharmacogenomics
    • 2.4.4 The Diagnostics
      • Therapeutics Fusion
    • 2.4.5 Potential Challenges
    • 2.4.6 Poor Metabolizer Phenotype Testing
    • 2.4.7 Drug Repositioning
  • 2.5 Pharmacogenomic Tests
    • 2.5.1 CYP2D6
    • 2.5.2 CYP2C19 and CYP2C9
    • 2.5.3 CYP3A4 and CYP3A5 Genotyping
    • 2.5.4 CYP1A2 and CYP2B6
    • 2.5.5 NAT2, DPD, and UGT1A1
  • 2.6 HercepTest
  • 2.7 Drivers of Pharmacogenomic Testing
  • 2.8 Pharmacogenomics and Drug Discovery
    • 2.8.1 Business Implications of Pharmacogenomics in Drug Discovery
    • 2.8.2 Impact of Pharmacogenomics on Drug Sales
    • 2.8.3 Pressure to Optimize Drug Discovery Drives Use of Pharmacogenomics
• 3. Pharmacogenomic Testing Market: Size, Growth and Share
  • 3.1 Global Pharmacogenomic Testing Markets by Technology Segments
    • 3.1.1 Market Structure
    • 3.1.2 Market Drivers in the Pharmacogenomic Diagnostics Testing Sector
    • 3.1.3 Market Restraints in Pharmacogenomic Diagnostic Testing Segment
    • 3.1.4 Principal Market Segments for Genomics Testing
      • 3.1.4.1 Diagnostic Testing
      • 3.1.4.2 Pharmacogenomic Testing
      • 3.1.4.3 SNP Identification
    • 3.1.5 Key Players in the Pharmacogenomic Diagnostics Testing Segment
    • 3.1.6 Pharmacogenomic Testing Sector Analysis
  • 3.2 U.S. Pharmacogenomic Testing Market
    • 3.2.1 Market Overview
    • 3.2.2 Diagnostic Testing Categories
  • 3.3 European Pharmacogenomic Diagnostic Testing Market
  • 3.4 Japanese Diagnostic Testing Market
• 4. Pharmacogenomic Disease Markers
  • 4.1 SNPs
    • 4.1.1 SNP Identification Market
    • 4.1.2 Overview of SNP Identification
    • 4.1.3 Strategies for SNP Identification
    • 4.1.4 Candidate Gene Selection
    • 4.1.5 Whole-Genome Linkage Disequilibrium Mapping
    • 4.1.6 SNP Databases
    • 4.1.7 Computational Tools for SNP Identification
    • 4.1.8 SNPbrowser, Applied Biosystems
    • 4.1.9 Progeny Suite, Progeny Software, LLC
    • 4.1.10 Sentrix Array Matrix, Illumina
    • 4.1.11 Third Wave Technologies (a Hologic Company)
  • 4.2 Predictive Pharmacogenomics
    • 4.2.1 Cancer Testing
    • 4.2.2 Breast Cancer
    • 4.2.3 Melanoma
    • 4.2.4 Colon Cancer
    • 4.2.5 Predictive Cancer Testing Market Size
    • 4.2.6 Prostate Cancer
    • 4.2.7 Lung Cancer
    • 4.2.8 Acute Myelocytic Leukemia (AML)
    • 4.2.9 Cystic Fibrosis
    • 4.2.10 Genetic Test for Cardiac Ion Channel Mutations (Cardiac Channelopathies)
    • 4.2.11 Cardiac Transplants
    • 4.2.12 Thiopurine S-methyltransferase (TPMT) Genetic Test
    • 4.2.13 CARING Study
    • 4.2.14 Vilazodone
    • 4.2.15 STRENGTH Trials (Statin Response Examined by Genetic HAP Markers)
    • 4.2.16 HIV and AIDS
    • 4.2.17 Herceptin and Tykerb
    • 4.2.18 Asthma
    • 4.2.19 Hepatitis C Viral Load
  • 4.3 Examining the Impact of Pharmacogenomics in Specific Disease Application
    • 4.3.1 The Impact of Pharmacogenomics in Bipolar and Other Psychiatric Disorders
    • 4.3.2 Pharmacogenomics in Warfarin Treatment
    • 4.3.3 Pharmacogenomics and Breast Cancer Treatment
    • 4.3.4 Pharmacogenomics of Depression
      • 4.3.4.1 Tricyclic Antidepressants
      • 4.3.4.2 Serotonin Re-uptake Inhibitors
      • 4.3.4.3 Mirtazapine and Venlafaxine
      • 4.3.4.4 Nefazodone, Moclobemide, Reboxetine and Trazodone
    • 4.3.5 Pharmacogenomics of Cardiovascular Disease
      • 4.3.5.1 Beta-blockers
      • 4.3.5.2 Angiotensin II Type 1 Receptor Antagonists and AT1 Receptor Antagonists (Sartans)
    • 4.3.6 Pharmacogenomics of Thromboembolic Disorders
      • 4.3.6.1 Warfarin
      • 4.3.6.2 Acenocoumarol
      • 4.3.6.3 Phenprocoumon
  • 4.4 Gene Chips to Detect Cytochrome Variations
    • 4.4.1 AmpliChip CYP450?Roche Diagnostics
    • 4.4.2 GeneChip System
      • Affymetrix
    • 4.4.3 NanoChip Molecular Biology Workstation?Nanogen, Inc
• 5. Pharmacogenomic Testing: Development Issues
  • 5.1 Adoption of Pharmacogenomic Testing
    • 5.1.1 Pharmacogenomics Gatekeepers
      • 5.1.1.1 Industry
      • 5.1.1.1.1 Use of Pharmacogenomics in Drug Development
      • 5.1.1.1.2 Co-development of Pharmacogenomics Diagnostics and Drugs
      • 5.1.1.2 FDA as a Gatekeeper of Pharmacogenomics
  • 5.2 Factors Influencing the Integration of Pharmacogenomics into Clinical Trials
  • 5.3 Moderators of Growth
    • 5.3.1 Classification of Extensive vs. Poor Metabolizer
    • 5.3.2 Genetic Testing
    • 5.3.3 Cost-Benefit of Pharmacogenomic Testing
    • 5.3.4 Workforce Issues
    • 5.3.5 Reimbursement
    • 5.3.6 New CPT Test Codes and Payment Amounts
    • 5.3.7 CMS and Other Third-party Payers
      • 5.3.7.1 Reimbursement Challenges to Pharmacogenomic Testing
      • 5.3.7.2 CMS Regulatory Responsibilities
      • 5.3.7.3 Costs Associated with Pharmacogenomic Testing
  • 5.4 Clinical Guidelines and Pharmacogenomic Testing
  • 5.5 Good Laboratory Practice (GLP)
  • 5.6 Quality Assurance Issues
    • 5.6.1 Criteria Required to Establish a Genomic Test for Clinical Use
    • 5.6.2 Microarrays in Clinical Diagnostic Use
  • 5.7 Pre-therapeutic Pharmacogenomic Testing
  • 5.8 Regulatory Requirements
  • 5.9 Screening
  • 5.10 Cost of Phenotyping vs. Genotyping
  • 5.11 Pharmacogenomic Tests: New Product Development
  • 5.12 Underutilization of Pharmacogenomic Tests
• 6. Business Trends in the Industry
  • 6.1 Pharmacogenomic Initiatives within Pharmaceutical Companies
  • 6.2 Pharmacogenomic Testing Growth Factors
  • 6.3 Acquisition, License Agreements, Internal Development and Partnerships
  • 6.4 Product Testing Depth in Pharmacogenomic Testing
  • 6.5 Government Regulation
    • 6.5.1 U.S. Regulations
    • 6.5.2 U.K. Regulations
    • 6.5.3 E.U. Regulations
    • 6.5.4 Japanese Regulations
  • 6.6 Increased Market Penetration in Pharmacogenomic Testing
  • 6.7 Legal Issues
    • 6.7.1 Federal Policy History
    • 6.7.2 State Policy History
    • 6.7.3 Federal Anti-Discrimination Laws and How They Apply to Genetics
      • 6.7.3.1 The Genetic Information Nondiscrimination Act of 2008 (GINA)
    • 6.7.4 Prescription Drug User Fee Act (PDUFA)
    • 6.7.5 Liability Concerns for Pharmacogenomics Drug and Diagnostic Developers
  • 6.8 Barriers to Growth
  • 6.9 Drivers of Growth
  • 6.10 Product Launches and Developments
  • 6.11 Investment Parameters for Diagnostic Companies
  • 6.12 Key Elements of the Pharmaceutical Value Chain
  • 6.13 An Evaluation of Successful Pharmacogenomic Business Models
  • 6.14 Ethical Considerations for Pharmacogenomic Applications
  • 6.15 Drug Repositioning Services
  • 6.16 Patent Protection of Pharmacogenomic Technology
  • 6.17 FDA Product Submission and Review Process
  • 6.18 FDA Pipeline for Pharmacogenomic Tests
  • 6.19 Adaptive Clinical Trial Design
• 7. Important Technology Trends in Pharmacogenomics
  • 7.1 Trends in Pharmacogenomic Testing
    • 7.1.1 Toxicogenomics
  • 7.2 Drug Metabolism
  • 7.3 Personalized Medicine: the Genomic and Proteomic Approach
  • 7.4 Biomarkers
    • 7.4.1 Cancer
      • 7.4.1.1 Leukemia: Gleevec and Dasatinib (BMS-354825)
      • 7.4.1.2 Gefitinib (Iressa)
      • 7.4.1.3 Colorectal Cancer
  • 7.5 Cardiovascular Drugs
    • 7.5.1 Arrhythmia
    • 7.5.2 Hypertension
    • 7.5.3 Hyperlipidemia
    • 7.5.4 Myocardial Infarction
    • 7.5.5 Heart Failure
  • 7.6 Future Developments
    • 7.6.1 GSK?s Pharmacogenomic Program
    • 7.6.2 Roche?s Biomarker Strategy
    • 7.6.3 Hypertension Markets
    • 7.6.4 Expression Data to Integrate Pharmacology and Chemistry Data
    • 7.6.5 Metabolomics
    • 7.6.6 Theranostics
• 8. Overview and Conclusions
  • 8.1 The Unrealized Promise of Pharmacogenomics
  • 8.2 The New Drug Pipeline
  • 8.3 Pharmacogenomics and Regulation
  • 8.4 Pharmacogenomics and Reimbursement
  • 8.5 Key Considerations for Realizing the Promise of Pharmacogenomics
  • 8.6 Development of Easy to Use Point of Care Pharmacogenomic Tests
  • 8.7 Development of Pharmacogenomic Tests during Drug Development
  • 8.8 Pharmacogenomics? Impact on Commercial Strategies
  • 8.9 Pharmacogenomics? Impact on the Blockbuster Model of Drug Development
  • 8.10 Pharmacogenomics? Impact on Clinical Trials
  • 8.11 Pharmacogenomic Business Models
  • 8.12 Structure of Pharmacogenomic Deals and Alliances
  • 8.13 Challenges to Pharmacogenomics
• 9. Company Profiles
  • 9.1 Abbott Laboratories
  • 9.2 Affymetrix
  • 9.3 Agilent Technologies, Inc
  • 9.4 Ambry Genetics
  • 9.5 ARCA Biopharma, Inc
  • 9.6 Asper Biotech
  • 9.7 AstraZeneca
  • 9.8 Bayer
  • 9.9 BioTrove, Inc
  • 9.10 Bristol-Myers Squibb
  • 9.11 Celera Group
  • 9.12 Clinical Data
  • 9.13 CombinatoRx, Inc
  • 9.14 Complement Genomics Ltd
  • 9.15 Covance Inc
  • 9.16 CuraGen Corporation
  • 9.17 Cypress Bioscience, Inc
  • 9.18 Dako (formerly DakoCytomation)
  • 9.19 deCODE Genetics
  • 9.20 DNAPrint Genomics
  • 9.21 DxS
  • 9.22 EraGen Biosciences
  • 9.23 EXACT Sciences
  • 9.24 Expression Analysis
  • 9.25 FivePrime Therapeutics
  • 9.26 GE Healthcare
  • 9.27 Gene Express, Inc
  • 9.28 GeneGO Inc
  • 9.29 Genelex Corporation
  • 9.30 Genentech
  • 9.31 Genizon Biosciences Inc
  • 9.32 Genomic Health
  • 9.33 Gentris
  • 9.34 Genzyme
  • 9.35 GlaxoSmithKline
  • 9.36 g-Nostics Ltd
  • 9.37 Hologic
  • 9.38 Human Genome Sciences
  • 9.39 Illumina
  • 9.40 Incyte, Inc
  • 9.41 InterGenetics Inc
  • 9.42 Interleukin Genetics
  • 9.43 Iris BioTechnologies Inc
  • 9.44 Johnson & Johnson
  • 9.45 Lab21
  • 9.46 Life Technologies Corporation
  • 9.47 Luminex Corp
  • 9.48 MediBIC Group
  • 9.49 Melior Discovery Inc
  • 9.50 Merck & Co
  • 9.51 Merck Serano
  • 9.52 Millennium Pharmaceuticals
  • 9.53 Monogram Biosciences, Inc
  • 9.54 Myriad Genetics, Inc
  • 9.55 Nanogen
  • 9.56 Nanosphere
  • 9.57 Nitromed
  • 9.58 Ocimum Biosolutions
  • 9.59 Orchid Cellmark
  • 9.60 Ore Pharmaceuticals
  • 9.61 PharmaSeq
  • 9.62 Prediction Sciences
  • 9.63 Predictive Biosciences
  • 9.64 Prometheus Laboratories
  • 9.65 Progeny Software, LLC
  • 9.66 Roche Diagnostics
  • 9.67 Response Genetics, Inc
  • 9.68 Sequenom
  • 9.69 SimuGen Ltd
  • 9.70 Sosei Group Corporation
  • 9.71 Transgenomic, Inc
  • 9.72 TrimGen Corp
  • 9.73 Tripos International
  • 9.74 Vertex Pharmaceuticals
  • 9.75 VIA Pharmaceuticals, Inc
  • 9.76 Warnex
  • 9.77 Wyeth
  • 9.78 XDx, Inc
• List of Figures
  • Figure 2.1: Roche AmpliChip
  • Figure 2.2: FDA Approval Rates for NME Drug Applications vs. R&D Expenditures, 1998-2008
  • Figure 2.3: Steps Involved in Bringing a Drug to Market
  • Figure 2.4: CYP2C9
  • Figure 6.1: Total Spending on Healthcare in the U.S., 1960-2008
  • Figure 6.2: The Healthcare Dollar, 2008
• List of Tables
  • Table 1.1: The Success of Pharmacogenomics: Drugs that Utilize Companion Tests, 2008
  • Table 2.1: The Difference between Pharmacogenomics and Pharmacogenetics
  • Table 2.2: Clinical Applications of Diagnostic Pharmacogenomic Testing
  • Table 2.3: Comparison of New Molecular Entity Outcomes for FDA and EMEA (Jan 2006 ? October 2008)
  • Table 2.4: Timeline for Development of Companion Diagnostics
  • Table 2.5: Valid Genomic Biomarkers in the Context of FDA-Approved Drug Labels
  • Table 2.6: Potential Benefits of Biomarkers as Companion Diagnostics in Drug Development
  • Table 2.7: Groups Participating in the International HapMap Project
  • Table 2.8: High-Profile Drug Withdrawals from the Marketplace
  • Table 2.9: Response Rates of Patients to a Major Drug for Selected Therapeutic Areas
  • Table 2.10 Factors That Determine a Successful Pharmacogenomic Test
  • Table 2.11: Pharmacogenomics? Influence on Drug Sales
  • Table 2.12: Pharmacogenomics? Effect on Maximizing R&D Productivity
  • Table 2.13: Prevalence of Metabolically-Active Enzymes
  • Table 2.14: Pharmacogenomics in Phase II and Phase III Trials
  • Table 2.15: Drug Testing
  • Table 2.16: Factors Affecting Variability in Individual Response to Drug Therapy
  • Table 2.17: CYP2D6 Characteristics
  • Table 2.18: CYP2D6 Metabolism of Drug Types
  • Table 2.19: CYP2C19
  • Table 2.20: CYP2C19 Metabolism of Drug Types
  • Table 2.21: CYP2C9 Characteristics
  • Table 2.22: CYP2C9 Metabolism of Drug Types
  • Table 2.23: CYP3A4/5/7 Metabolism of Drug Types
  • Table 2.24: CYP1A2 Metabolism of Drug Types
  • Table 2.25: CYP2B6 Metabolism of Drug Types
  • Table 2.26: Drivers of Pharmacogenomic Testing
  • Table 2.27: Markets for Pharmacogenomic Testing
  • Table 3.1: Worldwide Pharmacogenomic Market Size by Technology Segments, 2004?2012
  • Table 3.2: Total Pharmacogenomic Testing Market Size, 2001?2012
  • Table 3.3: Diagnostic Pharmacogenomic Testing Market Size, 2001?2012
  • Table 3.4: Benefits of Pharmacogenomic Diagnostics in Patient Care
  • Table 3.5: Genotyping Pharmacogenomic Testing Market Size, 2001?2012
  • Table 3.6: Benefits of Pharmacogenomics in Clinical Trials and Drug Development
  • Table 3.7: Five Key Action Points for Pharmaceutical Companies
  • Table 3.8: Global SNP Identification Tools Market Size, 2004?2012
  • Table 3.9: Pharmacogenomic Testing Market Structure
  • Table 3.10: P450 Isozymes and Pharmaceuticals
  • Table 3.11: List of Companies that Market Pharmacogenomic Tests
  • Table 3.12: Key Collaborations in the Pharmacogenomics Industry
  • Table 3.13: Prominent Drugs Withdrawn from the Market
  • Table 3.14: Key Elements in the Drug Development Process
  • Table 3.15: Major Suppliers of PCR-based Assays and PCR-based Technologies
  • Table 4.1: Methods for Performing NAT
  • Table 4.2: SNP Databases
  • Table 4.3: Myriad Genetics Predictive Medicine Sales, 2001?2008
  • Table 4.4: DNA-based Predictive Medicine Product Sales for Cancer, 2006?2010
  • Table 4.5: Developmental Atherosclerosis Drugs
  • Table 4.6: Summary of Assays for HIV Viral Load Testing
  • Table 4.7: U.S. Market Share of HIV Testing Kits
  • Table 4.8: Global HIV Statistics, 2007
  • Table 4.9: List of Approved HIV/AIDS Rapid Test Kits, 2009
  • Table 4.10: Monogram Bioscience, Inc. Products for HIV Testing
  • Table 4.11: CCR-5 Receptor Agonists in Development, 2009
  • Table 4.12: Asthma Therapeutic Drug Pipeline
  • Table 4.13: Psychiatric Case Studies, Organized Pharmacokinetically
  • Table 4.14: Antidepressant Drugs Decreased Clearance with DME CYP2D6
  • Table 4.15: Antidepressant Drugs with No Effect Clearance with DME CYP2D6
  • Table 5.1: Examples of Gene-Drug Pharmacogenomic Relationships
  • Table 5.2: Estimated Cost and Time for Typing of the BRCA1 Gene by Direct Sequencing vs. SNP Array
  • Table 5.3: Average Cost of Resistance Testing, 2007
  • Table 6.1: U.S. Prescription Drug Expenditures, 2003?2015
  • Table 6.2: U.S. Pharmaceutical Market, 1996?2009
  • Table 6.3: Top Ten Global Pharmaceutical Companies by Global Sales, 2007
  • Table 6.4: Pharmaceutical Companies Ranked by Total R&D Expenditures, 2007
  • Table 6.5: Leading Therapy Classes for R&D, 2008
  • Table 6.6: Leading Therapy Classes by Global Pharmaceutical Sales (Audited Market), 2007
  • Table 6.7: Number of NME Approvals and Mean Approval Times, 1984?2008
  • Table 6.8: Global Market for Tools and Consumables Used in Drug Discovery and Development, 1999?2010
  • Table 6.9: Leading Therapeutic Classes by U.S. Sales, 2006 and 2007
  • Table 6.10: Top Ten Therapeutic Classes by U.S. Dispensed Prescriptions, 2006 and 2007
  • Table 6.11: Top Ten Brand Drugs by U.S. Retail, 2007
  • Table 7.1: Select Companies Developing Cancer Diagnostics Available as Analyte Specific Reagents (ASRS)
  • Table 7.2: Emerging Fields in Biological Science with the Potential to Impact Personalized Medicine