Companion Diagnostics in Personalized Medicine and Cancer Therapy

Table of Contents

1 Overview

• 1.1 Statement of Report
• 1.2 About This Report
• 1.3 Scope of the Report
• 1.4 Objectives
• 1.5 Methodology
• 1.6 Executive Summary

2 Companion Diagnostics and Personalized Medicine

• 2.1 Scope of this Section
• 2.2 Introduction to Companion Diagnostics and Personalized Medicine
• 2.3 Drug Metabolism and Companion Diagnostics and Personalized Medicine
• 2.4 Examples of Personalized Medicine and Companion Diagnostic Tests
• 2.5 Personalized Medicine and Companion Diagnostic Testing Product Pipeline
• 2.6 The Personalized Medicine Coalition (PMC)
• 2.7 Regulatory Trends and Guidelines in the Personalized Medicine Space
  • 2.7.1 The Changing Regulatory Landscape for Personalized Medicine
• 2.8 Companion Diagnostics Play an Increasing Role in Cancer Care
• 2.9 Specific Examples of Clinical Situations Where Companion Diagnostics Are Being Deployed
  • 2.9.1 Epidermal Growth Factor Receptor (EGFR) Assay
  • 2.9.2 Individualized Warfarin Therapy
  • 2.9.3 UGT1A1 Molecular Assay for Camptosar
  • 2.9.4 Response to Gleevec in GIST
  • 2.9.5 LabCorp, ARCA Personalized Medicine Deal for Cardiovascular Diseases
  • 2.9.6 Osmetech Licenses Epidauros Biotechnologie AG CYP2D6 Biomarker to Enter Companion Diagnostics
• 2.10 Diagnostic Tests for Personalized Analysis of Cancer Therapy Effectiveness

3 Companion Diagnostics: Qualitative and Quantitative Market Analysis

• 3.1 Market Analysis of Molecular Diagnostics and Companion Diagnostics
• 3.2 Costs of Companion Diagnostics in Healthcare Expenditures
• 3.3 Molecular Diagnostic Market
• 3.4 Molecular Diagnostics Technology Platforms and Their Impact on Clinical Medicine
• 3.5 Snapshot of Companion Diagnostics Industry Structure
• 3.6 The Case for Theranostics
• 3.7 Companion Diagnostics Market Analysis-Market Survey Data Characterizing the Qualitative and Quantitative Industry Parameters

4 Trends and Overview

• 4.1 Companion Diagnostics: Industry SWOT Analysis
• 4.2 Macro Trends in Companion Diagnostics
• 4.3 Challenges for Companion Diagnostics Development
• 4.4 Timeline for Impact of Various Segments in Companion Diagnostics
• 4.5 Use of Proteomics to Develop Individualized Tests
• 4.6 The Market Problem: Finding Value with Diagnostics for Personalized Medicine

5 Biomarker Tests Co-developed with Cancer Therapeutics as Companion Diagnostics

• 5.1 Sector Overview
  • 5.1.1 Impact of New Technology Platforms
  • 5.1.2 Impact on Drug Discovery
  • 5.1.3 Biomarkers as Endpoints in Drug Discovery
  • 5.1.4 Targeted Therapy
• 5.2 Companion Diagnostics on the Market
• 5.3 Epidermal Growth Factor Receptor Companions
  • 5.3.1 Bevacizamab (Avastin)
  • 5.3.2 EGFR for Colorectal Cancer and Camptosar (Irinotecan)
  • 5.3.3 EGFR Express and Erbitux (Cetuximab)
  • 5.3.4 HER2 and Heceptin (Trastuzumab)
  • 5.3.5 Iressa and Tarceva Companion Test
  • 5.3.6 Tykerb (GSK), and Vectibix™ (Amgen) Companion Tests
  • 5.3.7 EGFRx Assay
  • 5.3.8 Monogram eTag
  • 5.3.9 Veripath OncoDiagnostics EGFR PharmDX
• 5.4 Myriad' s TheraGuide 5-FU
• 5.5 Companions for Tyrosine Kinase Inhibitors: Erlotinib and Gefitinib
  • 5.5.1 TheraScreen: EGFR29
  • 5.5.2 The K-RAS Mutation Detection Kit
• 5.6 Irinotecan and UGT1A1
• 5.7 Gleevec (Imatinib) Companions
  • 5.7.1 DakoCytomation' s c-Kit (9.7) pharmDx
• 5.8 Companion Diagnostics Involving Metabolizing Enzymes
  • 5.8.1 Companions for TMPT, CYP2C9, and UGT1A1 Enzymes
  • 5.8.2 Companions for Aromatase Inhibitors
  • 5.8.3 Companions for Actos and Avandia
• 5.9 Drivers and Barriers to Companion Diagnostics
• 5.10 Partnerships with Pharma Companies to Identify Therapeutic Targets
• 5.11 Circulating Tumor Cell Assay: Prognostic and Predictive Factors for Breast Cancer
• 5.12 Companion Diagnostics Used by Clinical Service Laboratories
• 5.13 New Technologies and Products under Development
  • 5.13.1 OncoMethylome
• 5.14 Blood-Based Technologies
  • 5.14.1 Oncotech
• 5.15 Monogram Biosciences HIV Personalized Platform
• 5.16 Wako LBA¥AFP Test for Liver Cancer
• 5.17 Future Developments for Companion Diagnostics

6 Business and Regulatory Trends in the Companion Biomarker Testing Sector

• 6.1 Industry Consolidation
• 6.2 Breath of Product Offering and Pricing
• 6.3 Government Regulation of Medical Devices
  • 6.3.1 FDA Guidance on Drug Test Co-development
  • 6.3.2 Device Classes
  • 6.3.3 Investigational Use of IVDM Assays
  • 6.3.4 Post-market Requirements
• 6.4 Strategic Business and Marketing Considerations
• 6.5 Commercial Opportunities in Companion Markers
• 6.6 Moderators of Growth
  • 6.6.1 Roadblocks to Integrating Companion Biomarkers into Clinical Practice
  • 6.6.2 Management of Targeted Therapeutics by Third-Party Payers
• 6.7 Biotechnology Industry Trends
• 6.8 Pharmaceutical Industry Trends
• 6.9 Acquisition, License Agreement, Partnerships
• 6.10 Legal Developments
• 6.11 Sales and Marketing Strategies for Tumor Marker Tests
• 6.11.1 International Markets
• 6.12 Product Commercialization
• 6.13 Reimbursement
• 6.14 Self-Referral Rules
• 6.15 Health Insurance Portability and Accountability Act
• 6.16 Clinical Laboratory Improvement Amendments (CLIA)
• 6.17 In Vitro Diagnostic Directive (IVDD) and Medical Device Regulations
• 6.18 FDA' s Quality System Regulation (QSR)
• 6.19 FDA' S OIVD on IVDMIAs
• 6.20 FDA' s Qualification of Cancer Biomarkers
• 6.20.1 Regulatory Perspectives of Biomarker Validation
• 6.21 Genetic Tests and Medical Records
  • 6.21.1 Laws against Genetic Discrimination
• 6.22 Medicare Reimbursement
• 6.22.1 Medicare Part B Spending Trends
• 6.23 Global Drivers of Clinical Laboratory Testing
• 6.24 Global Outlook
• 6.25 Oncology Biomarker Qualification Initiative
• 6.26 FDA Critical Path
• 6.27 Biomarkers and FDA' s Voluntary Genomic Data Submission
• 6.28 From Personalized to Predictive Medicine
• 6.29 Analysis of Cost-Effectiveness at the Individual Level
• 6.30 The Patient and Advocate Perspective: An Evolution of Influence
• 6.31 Real-World Experiences Translating the Vision of Personalized Medicine into Practice

7 Companies Entering the Companion Diagnostics Market

• 7.1 Industry Overview
• 7.2 Representative Companion Diagnostic Development Companies
  • 7.2.1 20/20 GeneSystems
  • 7.2.2 Abbott Diagnostics
  • 7.2.3 Affymetrix
  • 7.2.4 Agendia BV
  • 7.2.5 Agensys
  • 7.2.6 Almac Group
  • 7.2.7 AMDL
  • 7.2.8 Arcturus Bioscience (acquired by Molecular Devices)
  • 7.2.9 Aureon Laboratories
  • 7.2.10 BD
  • 7.2.11 Beckman Coulter
  • 7.2.12 Biocode Hycel
  • 7.2.13 BioCurex
  • 7.2.14 Biomarker Technologies
  • 7.2.15 Biomedical Diagnostics
  • 7.2.16 Biomerica
  • 7.2.17 bioMérieux
  • 7.2.18 BioModa
  • 7.2.19 Bruker Daltonics
  • 7.2.20 Cangen Biotechnologies
  • 7.2.21 Caprion Proteomics
  • 7.2.22 Celera Diagnostics
  • 7.2.23 Cepheid
  • 7.2.24 Claros Diagnostics
  • 7.2.25 Clinical Data: PGxHealth and Cogenics
  • 7.2.26 Ciphergen Biosystems renamed Vermillion, Inc.
  • 7.2.27 Clarient
  • 7.2.28 Correlogic Systems
  • 7.2.29 CytoCore
  • 7.2.30 Cytogen
  • 7.2.31 Cytyc Corporation
  • 7.2.32 Dako (formerly DakoCytomation)
  • 7.2.33 DiaDexus
  • 7.2.34 Digene (acquired by Qiagen)
  • 7.2.35 DiagnoCure
  • 7.2.36 Diagnostic Systems Laboratories (acquired by Beckman Coulter)
  • 7.2.37 DRG International
  • 7.2.38 DxS
  • 7.2.39 EDP Biotech
  • 7.2.40 Epigenomics
  • 7.2.41 EXACT Sciences Corporation
  • 7.2.42 Exagen Diagnostics
  • 7.2.43 Gene Logic
  • 7.2.44 Genesis Genomics
  • 7.2.45 Genomic Health
  • 7.2.46 Gen-Probe
  • 7.2.47 Health Discovery Corporation
  • 7.2.48 Ikonisys
  • 7.2.49 Immunicon
  • 7.2.50 Immunomedics
  • 7.2.51 Incyte
  • 7.2.52 InterGenetics
  • 7.2.53 Ipsogen
  • 7.2.54 LabCorp
  • 7.2.55 Matritech
  • 7.2.56 Miraculins
  • 7.2.57 Mitsubishi Kagaku latron
  • 7.2.58 Monogram Biosciences
  • 7.2.59 Myriad Genetics
  • 7.2.60 NimbleGen Systems
  • 7.2.61 Northwest Biotherapeutics
  • 7.2.62 Nycomed
  • 7.2.63 Oncotech
  • 7.2.64 Oncothyreon (formerly known as Biomira)
  • 7.2.65 Orion Genomics
  • 7.2.66 Oxford Genome Sciences
  • 7.2.67 Panacea Pharmaceuticals
  • 7.2.68 Perlegen Sciences
  • 7.2.69 Polymedco
  • 7.2.70 Power3 Medical Products
  • 7.2.71 Prometheus
  • 7.2.72 Proteome Systems
  • 7.2.73 Qiagen
  • 7.2.74 Sanko Junyaku
  • 7.2.75 SensiGen
  • 7.2.76 SuperArray Bioscience
  • 7.2.77 Third Wave Technologies
  • 7.2.78 Tosoh Biosciences
  • 7.2.79 TrimGen
  • 7.2.80 TriPath Imaging (acquired by BD)
  • 7.2.81 Upstream Biosciences
  • 7.2.82 Ventana Medical Systems
  • 7.2.83 Veridex

Appendix 1: FDA Guidance for Industry: Pharmacogenomic Data Submission (March 2005)

Appendix 2: Histochemical Markers for Cancer

LIST OF TABLES

• Table 2.1: Timeline for Development of Companion Diagnostics
• Table 2.2: Personalized Medicine at the Nexus Point
• Table 2.3: Percentage of Non-Responders in Various Drug Classes
• Table 2.4: High-Profile Drug Withdrawals from the Marketplace
• Table 2.5: Metabolism of Drugs by Hepatic Enzymes
• Table 2.6: Drug Metabolism Drives Drug Efficacy/Toxicity
• Table 2.7: Population Frequency of the Various Cytochromes
• Table 2.8: Selected List of Personalized Medicine Tests
• Table 2.9: Personalized Medicine Product Pipeline
• Table 2.10: Marketed Personalized Therapies in 2006
• Table 2.11: Typical Response Rates in Therapeutic Areas
• Table 2.12: Prevalence of People Taking Medications Metabolized by Liver Enzymes
• Table 2.13: UGT1A1 Helps to Determine Risks Associated with Irinotecan
• Table 2.14: Current Product Labels: Enzyme Metabolism
• Table 3.1: Timeline for Impact of Various Molecular Diagnostics Technologies on Personalized Medicine
• Table 3.2: Impact of Molecular Diagnostics Technologies on Therapeutic Areas in Personalized Medicine
• Table 3.3: Challenges of Various Molecular Diagnostics Technology Platforms in Personalized Medicine
• Table 3.4: FDA Classification of Diagnostics by Risk
• Table 4.1: Personalized Medicine Industry SWOT Analysis
• Table 4.2: Market Opportunities in Personalized Medicine
• Table 4.3: Challenges for Market Adoption of Various Personalized Medicine Tests
• Table 4.4: Hurdles to Personalized Medicine and Companion Diagnostics Development
• Table 4.5: Timeline of Impact in Areas of Personalized Medicine
• Table 4.6: Impact of Personalized Medicine on Various Therapeutic Areas
• Table 5.1: Potential Benefits of Biomarkers as Companion Diagnostics
• Table 5.2: Utility of Biomarker as Companion Diagnostics to Drug Development
• Table 5.3: ASCO-CAP Guidelines for HER2 Testing in Breast Cancer: How to Interpret Test Results
• Table 5.4: Device Submission Elements for the FDA
• Table 6.1: List and Discounted Prices for Abbott Tumor Marker Tests
• Table 6.2: Medicare Spending on Clinical Lab Services, 1996 to 2005
• Table 6.3: Hospital Laboratory Share of Part B Medicare Spending, 1996 to 2005
• Table 6.4: Medicare Part B Lab Spending Per Medicare Enrollee, 1998 to 2005
• Table 6.5: Summary of Biomarker Use in the Commercialization of Novel Oncology Pharmacotherapeutics
• Table 6.6: Pharmacoeconomic Challenges to the Implementation of Biomarkers as Companion Diagnostic Tests
• Table 7.1: Major Players in Companion Diagnostic Sector
• Table 7.2: Tumor Diagnosis Immunoassay
• Table 7.3: Tumor Diagnosis Radioimmunoassay
• Table 7.4: Summary of Matritech' s Product Development Programs

LIST OF FIGURES

• Figure 2.1: Personalizing Drug Treatment
• Figure 2.2: Approaches to Personalized Medicine
• Figure 2.3: The Phase I and II Processes of Drug Metabolism
• Figure 2.4: Hepatic Distribution of Human CYP450
• Figure 2.5: Relative Contribution of CYP450 Enzymes to Drug Metabolism
• Figure 2.6: Genetic Components Determine Drug Metabolism
• Figure 2.7: Personalized Medicine Drugs in Development
• Figure 3.1: From Genetic Content to Personalized Medicine
• Figure 3.2: Impact of Diagnostic Testing on Healthcare Decision Making
• Figure 3.3: Impact of Diagnostic Testing on Healthcare Spending
• Figure 3.4: Breakout of the Molecular Diagnostics Marketplace by Country
• Figure 3.5: Breakout of the Molecular Diagnostics Marketplace by Vendor
• Figure 3.6: Molecular Diagnostics Market Segmentation
• Figure 3.7: Molecular Diagnostics Market Segmentation by Technology
• Figure 3.8: Market Survey Respondent Demographics
• Figure 3.9: Breakout of the Respondent Pool by Affiliation
• Figure 3.10: Segmentation of the Personalized Medicine Market
• Figure 4.1: Personalized Medicine Market Drivers
• Figure 4.2: Challenges in the Personalized Medicine Space
• Figure 5.1: Carcinogenesis Is a Multi-Step Process
• Figure 5.2: ASCO-CAP Guidelines for HER2 Testing in Breast Cancer: Equivocal Results with IHC
• Figure 5.3: ASCO-CAP Guidelines for HER2 Testing in Breast Cancer: Results by FISH
• Figure 5.4: MGMT Methylation Status Correlates to Survival Rate
• Figure 6.1: Part B Spending on Clinical Lab Services, 1991 to 2005