Market Report Source

Overview

A near-term market opportunity for cancer companion diagnostic tests exists in drug selection for cancer therapy. Co-development of molecular diagnostics and targeted therapeutics has already been proven to be a successful strategy in the development of novel anti-cancer drugs. Adoption of biomarker development in clinical research provides great opportunities to identify patient subpopulations with differential drug responses and to uncover the underlying mechanisms. These data could help to explain if clinical trials of new drugs are adequate, and offer the possibility of creating a clear prescription path based on predictive biomarkers.

The purpose of this TriMark Publications report is to describe the specific segment of the diagnostics market that develops new technology platforms for evaluating the metabolism of therapeutic agents, or for evaluating which therapeutic regimes are most effective for a particular type of disease. The term companion diagnostic means that the particular diagnostic test under evaluation is specifically linked to a known therapeutic drug. This linkage could be important in the therapeutic application and clinical outcome of a drug (personalized medicine), or an important component of the drug development process. This report focuses on the former linkage, i.e., the use of companion diagnostic tests in personalized medicine.

Table of Contents

1 Overview 7
1.1 Statement of Report 7
1.2 About This Report 7
1.3 Scope of the Report 7
1.4 Objectives 8
1.5 Methodology 9
1.6 Executive Summary 10

2 Companion Diagnostics and Personalized Medicine 14
2.1 Scope of this Section 14
2.2 Introduction to Companion Diagnostics and Personalized Medicine 14
2.3 Drug Metabolism and Companion Diagnostics and Personalized Medicine 18
2.4 Examples of Personalized Medicine and Companion Diagnostic Tests 22
2.5 Personalized Medicine and Companion Diagnostic Testing Product Pipeline 25
2.6 The Personalized Medicine Coalition (PMC) 27
2.7 Regulatory Trends and Guidelines in the Personalized Medicine Space 29
2.7.1 The Changing Regulatory Landscape for Personalized Medicine 30
2.8 Companion Diagnostics Play an Increasing Role in Cancer Care 32
2.9 Specific Examples of Clinical Situations Where Companion Diagnostics Are Being Deployed 32
2.9.1 Epidermal Growth Factor Receptor (EGFR) Assay 33
2.9.2 Individualized Warfarin Therapy 35
2.9.3 UGT1A1 Molecular Assay for Camptosar 36
2.9.4 Response to Gleevec in GIST 36
2.9.5 LabCorp, ARCA Personalized Medicine Deal for Cardiovascular Diseases 36
2.9.6 Osmetech Licenses Epidauros Biotechnologie AG CYP2D6 Biomarker to Enter Companion Diagnostics 36
2.10 Diagnostic Tests for Personalized Analysis of Cancer Therapy Effectiveness 37

3 Companion Diagnostics: Qualitative and Quantitative Market Analysis 38
3.1 Market Analysis of Molecular Diagnostics and Companion Diagnostics 38
3.2 Costs of Companion Diagnostics in Healthcare Expenditures 39
3.3 Molecular Diagnostic Market 40
3.4 Molecular Diagnostics Technology Platforms and Their Impact on Clinical Medicine 42
3.5 Snapshot of Companion Diagnostics Industry Structure 44
3.6 The Case for Theranostics 45
3.7 Companion Diagnostics Market Analysis-Market Survey Data Characterizing the Qualitative and Quantitative Industry Parameters 46

4 Trends and Overview 49
4.1 Companion Diagnostics: Industry SWOT Analysis 49
4.2 Macro Trends in Companion Diagnostics 49
4.3 Challenges for Companion Diagnostics Development 52
4.4 Timeline for Impact of Various Segments in Companion Diagnostics 53
4.5 Use of Proteomics to Develop Individualized Tests 55
4.6 The Market Problem: Finding Value with Diagnostics for Personalized Medicine 56
5 Biomarker Tests Co-developed with Cancer Therapeutics as Companion Diagnostics 58

5.1 Sector Overview 58
5.1.1 Impact of New Technology Platforms 58
5.1.2 Impact on Drug Discovery 59
5.1.3 Biomarkers as Endpoints in Drug Discovery 59
5.1.4 Targeted Therapy 61
5.2 Companion Diagnostics on the Market 62
5.3 Epidermal Growth Factor Receptor Companions 62
5.3.1 Bevacizamab (Avastin) 63
5.3.2 EGFR for Colorectal Cancer and Camptosar (Irinotecan) 64
5.3.3 EGFR Express and Erbitux (Cetuximab) 64
5.3.4 HER2 and Heceptin (Trastuzumab) 65
5.3.5 Irressa and Tarceva Companion Test 67
5.3.6 Tykerb (GSK), and Vectibix™ (Amgen) Companion Tests 67
5.3.7 EGFRx Assay 68
5.3.8 Monogram eTag 69
5.3.9 Veripath OncoDiagnostics EGFR PharmDX 69
5.4 Myriad’s TheraGuide 5-FU 69
5.5 Companions for Tyrosine Kinase Inhibitors: Erlotinib and Gefitinib 70
5.5.1 TheraScreen: EGFR29 70
5.5.2 The K-RAS Mutation Detection Kit 70
5.6 Irinotecan and UGT1A1 70
5.7 Gleevec (Imatinib) Companions 70
5.7.1 DakoCytomation’s c-Kit (9.7) pharmDx 71
5.8 Companion Diagnostics Involving Metabolizing Enzymes 71
5.8.1 Companions for TMPT, CYP2C9, and UGT1A1 Enzymes 71
5.8.2 Companions for Aromatase Inhibitors 72
5.8.3 Companions for Actos and Avandia 72
5.9 Drivers and Barriers to Companion Diagnostics 73
5.10 Partnerships with Pharma Companies to Identify Therapeutic Targets 73
5.11 Circulating Tumor Cell Assay: Prognostic and Predictive Factors for Breast Cancer 74
5.12 Companion Diagnostics Used by Clinical Service Laboratories 74
5.13 New Technologies and Products under Development 75
5.13.1 OncoMethylome 75
5.14 Blood-Based Technologies 77
5.14.1 Oncotech 77
5.15 Monogram Biosciences HIV Personalized Plaftorm 78
5.16 Wako LBA\AFP Test for Liver Cancer 78
5.17 Future Developments for Companion Diagnostics 78

6 Business and Regulatory Trends in the Companion Biomarker Testing Sector 80
6.1 Industry Consolidation 80
6.2 Breath of Product Offering and Pricing 81
6.3 Government Regulation of Medical Devices 81
6.3.1 FDA Guidance on Drug Test Co-development 83
6.3.2 Device Classes 83
6.3.3 Investigational Use of IVDM Assays 83
6.3.4 Post-market Requirements 84
6.4 Strategic Business and Marketing Considerations 85
6.5 Commercial Opportunities in Companion Markers 86
6.6 Moderators of Growth 87
6.6.1 Roadblocks to Integrating Companion Biomarkers into Clinical Practice 87
6.6.2 Management of Targeted Therapeutics by Third-Party Payers 88
6.7 Biotechnology Industry Trends 88
6.8 Pharmaceutical Industry Trends 88
6.9 Acquisition, License Agreement, Partnerships 89
6.10 Legal Developments 92
6.11 Sales and Marketing Strategies for Tumor Marker Tests 93
6.11.1 International Markets 95
6.12 Product Commercialization 97
6.13 Reimbursement 97
6.14 Self-Referral Rules 98
6.15 Health Insurance Portability and Accountability Act 99
6.16 Clinical Laboratory Improvement Amendments (CLIA) 100
6.17 In Vitro Diagnostic Directive (IVDD) and Medical Device Regulations 100
6.18 FDA’s Quality System Regulation (QSR) 101
6.19 FDA’S OIVD on IVDMIAs 102
6.20 FDA’s Qualification of Cancer Biomarkers 103
6.20.1 Regulatory Perspectives of Biomarker Validation 103
6.21 Genetic Tests and Medical Records 103
6.21.1 Laws against Genetic Discrimination 104
6.22 Medicare Reimbursement 104
6.22.1 Medicare Part B Spending Trends 104
6.23 Global Drivers of Clinical Laboratory Testing 106
6.24 Global Outlook 107
6.25 Oncology Biomarker Qualification Initiative 108
6.26 FDA Critical Path 109
6.27 Biomarkers and FDA’s Voluntary Genomic Data Submission 109
6.28 From Personalized to Predictive Medicine 109
6.29 Analysis of Cost-Effectiveness at the Individual Level 109
6.30 The Patient and Advocate Perspective: An Evolution of Influence 109
6.31 Real-World Experiences Translating the Vision of Personalized Medicine into Practice 109

7 Companies Entering the Companion Diagnostics Market 111
7.1 Industry Overview 111
7.2 Representative Companion Diagnostic Development Companies 111
7.2.1 20/20 GeneSystems 113
7.2.2 Abbott Diagnostics 113
7.2.3 Affymetrix 115
7.2.4 Agendia BV 117
7.2.5 Agensys 118
7.2.6 Almac Group 118
7.2.7 AMDL 118
7.2.8 Arcturus Bioscience 120
7.2.9 Aureon Biosciences 120
7.2.10 Beckman Coulter 121
7.2.11 Biocode S.A. 122
7.2.12 BioCurex 122
7.2.13 Biomarker Technologies 123
7.2.14 Biomedical Diagnostics 123
7.2.15 Biomerica 123
7.2.16 bioMérieux 124
7.2.17 Biomira 124
7.2.18 BioModa 125
7.2.19 Bruker Daltonics 125
7.2.20 Byk Gulden 126
7.2.21 Cangen Biotechnologies 126
7.2.22 Caprion Proteomics 127
7.2.23 Celera Diagnostics 127
7.2.24 Cepheid 128
7.2.25 Claros Diagnostics 129
7.2.26 Clinical Data: PGxHealth and Cogenics 129
7.2.27 Ciphergen Biosystems 131
7.2.28 Clarient 132
7.2.29 Correlogic Systems 133
7.2.30 Cytogen 133
7.2.31 Cytyc Corporation 136
7.2.32 Dako 136
7.2.33 DiaDexus LLC 137
7.2.34 Digene Corporation 138
7.2.35 DiagnoCure 138
7.2.36 Diagnostic Systems Laboratories 139
7.2.37 DRG International 139
7.2.38 DxS 140
7.2.39 EDP Biotech 141
7.2.40 Epigenomics 142
7.2.41 Exact Sciences Corporation 142
7.2.42 Exagen Diagnostics 143
7.2.43 Gene Logic 144
7.2.44 Genesis Genomics 144
7.2.45 Genomic Health 145
7.2.46 Gen-Probe 145
7.2.47 Health Discovery Corporation 146
7.2.48 Ikonisys 146
7.2.49 Immunicon 147
7.2.50 Immunomedics 150
7.2.51 Incyte Pharmaceuticals 151
7.2.52 InterGenetics 152
7.2.53 Ipsogen 152
7.2.54 LabCorp 152
7.2.55 Matritech 153
7.2.56 Miraculins 156
7.2.57 Mitsubishi Kagaku Medical 156
7.2.58 Molecular Diagnostics (CytoCore) 156
7.2.59 Monogram Biosciences 157
7.2.60 Myriad Genetics 157
7.2.61 NimbleGen Systems 161
7.2.62 Northwest Biotherapeutics 161
7.2.63 Oncotech 162
7.2.64 Orion Genomics 163
7.2.65 Oxford Genome Sciences 163
7.2.66 Panacea Pharmaceuticals 164
7.2.67 Perlegen Sciences 164
7.2.68 Polymedco 164
7.2.69 Power3 Medical Products 165
7.2.70 Prometheus 165
7.2.71 Proteome Systems 165
7.2.72 Qiagen 166
7.2.73 Sanko Junyaku 167
7.2.74 SensiGen 167
7.2.75 SuperArray Bioscience 167
7.2.76 Third Wave Technologies 167
7.2.77 Tosoh Medics 168
7.2.78 TrimGen 168
7.2.79 TriPath Imaging 168
7.2.80 Upstream Biosciences 170
7.2.81 Ventana Medical Systems 170
7.2.82 Veridex 171

Appendix 1: FDA Guidance for Industry: Pharmacogenomic Data Submission (March 2005) 173
Appendix 2: Histochemical Markers for Cancer 185

LIST OF TABLES
Table 2.1: Timeline for Development of Companion Diagnostics 15
Table 2.2: Personalized Medicine at the Nexus Point 16
Table 2.3: Percentage of Non-Responders in Various Drug Classes 17
Table 2.4: High-Profile Drug Withdrawals from the Marketplace 17
Table 2.5: Metabolism of Drugs by Hepatic Enzymes 19
Table 2.6: Drug Metabolism Drives Drug Efficacy/Toxicity 22
Table 2.7: Population Frequency of the Various Cytochromes 22
Table 2.8: Selected List of Personalized Medicine Tests 24
Table 2.9: Personalized Medicine Product Pipeline 26
Table 2.10: Marketed Personalized Therapies in 2006 27
Table 2.11: Typical Response Rates in Therapeutic Areas 33
Table 2.12: Prevalence of People Taking Medications Metabolized by Liver Enzymes 34
Table 2.13: UGT1A1 Helps to Determine Risks Associated with Irinotecan 34
Table 2.14: Current Product Labels: Enzyme Metabolism 35
Table 3.1: Timeline for Impact of Various Molecular Diagnostics Technologies on Personalized Medicine 43
Table 3.2: Impact of Molecular Diagnostics Technologies on Therapeutic Areas in Personalized Medicine 43
Table 3.3: Challenges of Various Molecular Diagnostics Technology Platforms in Personalized Medicine 44
Table 3.4: FDA Classification of Diagnostics by Risk 46
Table 4.1: Personalized Medicine Industry SWOT Analysis 49
Table 4.2: Market Opportunities in Personalized Medicine 51
Table 4.3: Challenges for Market Adoption of Various Personalized Medicine Tests 52
Table 4.4: Hurdles to Personalized Medicine and Companion Diagnostics Development 53
Table 4.5: Timeline of Impact in Areas of Personalized Medicine 54
Table 4.6: Impact of Personalized Medicine on Various Therapeutic Areas 55
Table 5.1: Potential Benefits of Biomarkers as Companion Diagnostics 60
Table 5.2: Utility of Biomarker as Companion Diagnostics to Drug Development 61
Table 5.3: ASCO-CAP Guidelines for HER2 Testing in Breast Cancer: How to Interpret Test Results 65
Table 5.4: Device Submission Elements for the FDA 73
Table 6.1: List and Discounted Prices for Abbott Tumor Marker Tests 81
Table 6.2: Medicare Spending on Clinical Lab Services, 1996 to 2005 105
Table 6.3: Hospital Laboratory Share of Part B Medicare Spending, 1996 to 2005 106
Table 6.4: Medicare Part B Lab Spending Per Medicare Enrollee, 1998 to 2005 106
Table 6.5: Summary of Biomarker Use in the Commercialization of Novel Oncology Pharmacotherapeutics 110
Table 6.6: Pharmacoeconomic Challenges to the Implementation of Biomarkers as Companion Diagnostic Tests 110
Table 7.1: Major Players in Companion Diagnostic Sector 111
Table 7.2: Tumor Diagnosis Immunoassay 140
Table 7.3: Tumor Diagnosis Radioimmunoassay 140
Table 7.4: Summary of Matritech’s Product Development Programs 155

LIST OF FIGURES
Figure 2.1: Personalizing Drug Treatment 14
Figure 2.2: Approaches to Personalized Medicine 15
Figure 2.3: The Phase I and II Processes of Drug Metabolism 18
Figure 2.4: Hepatic Distribution of Human CYP450 19
Figure 2.5: Relative Contribution of CYP450 Enzymes to Drug Metabolism 20
Figure 2.6: Genetic Components Determine Drug Metabolism 20
Figure 2.7: Personalized Medicine Drugs in Development 25
Figure 3.1: From Genetic Content to Personalized Medicine 39
Figure 3.2: Impact of Diagnostic Testing on Healthcare Decision Making 39
Figure 3.3: Impact of Diagnostic Testing on Healthcare Spending 40
Figure 3.4: Breakout of the Molecular Diagnostics Marketplace by Country 40
Figure 3.5: Breakout of the Molecular Diagnostics Marketplace by Vendor 41
Figure 3.6: Molecular Diagnostics Market Segmentation 42
Figure 3.7: Molecular Diagnostics Market Segmentation by Technology 42
Figure 3.8: Market Survey Respondent Demographics 46
Figure 3.9: Breakout of the Respondent Pool by Affiliation 47
Figure 3.10: Segmentation of the Personalized Medicine Market 47
Figure 4.1: Personalized Medicine Market Drivers 50
Figure 4.2: Challenges in the Personalized Medicine Space 50
Figure 5.1: Carcinogenesis Is a Multi-Step Process 59
Figure 5.2: ASCO-CAP Guidelines for HER2 Testing in Breast Cancer: Equivocal Results with IHC 66
Figure 5.3: ASCO-CAP Guidelines for HER2 Testing in Breast Cancer: Results by FISH 66
Figure 5.4: MGMT Methylation Status Correlates to Survival Rate 76
Figure 6.1: Part B Spending on Clinical Lab Services, 1991 to 2005 105