Market Report Source

Overview

Until superior therapeutic treatments are developed to prevent, treat and cure cancer, the best means of reducing mortality and morbidity in a disease this complex is early detection and diagnosis. In the major solid cancer types such as lung, breast, colon and prostate, long-term survival rates drop precipitously once metastatis has occurred. The case is clear for development of biomarkers for early detection and screening tests for diseases such as breast, colon, ovarian and lung cancer. In addition, diagnostic measurement of cancer disease progression is essential to successful disease management. For these reasons, development of new and effective biomarkers for cancer detection and diagnosis is central to the cancer problem. The use of nucleic acid biomarker diagnostics have begun to answer these questions. Protein biomarkers are also useful.

The purpose of this TriMark Publications report is to describe the specific segment of the cancer diagnostics market which develops new biomarker technology platforms for diagnosing and treating cancer. Biomarkers are useful in following the course of cancer and evaluating which therapeutic regimes are most effective for a particular type of cancer, as well as determining long-term susceptibility to cancer or recurrence. This study particularly examines those clinical measurement devices, and their reagents and supplies, which are meant to be used in hospitals, clinics, commercial laboratories and doctor’s offices to diagnose and monitor cancer. The examination also provides an in-depth discussion of the application of biomarkers in developing novel targeted cancer therapeutics, their predication response and efficacy, as well as their use in diagnosis of cancer.

The main objectives of this analysis are:

• Identifying viable technology drivers for cancer biomarkers and related companion diagnostics through a comprehensive look at platform technologies including, probe-based nucleic acid assays, microarrays and sequencing, and mass spectroscopy.

• Obtaining a complete understanding of the new cancer biomarker diagnostic tests-i.e., predictive, screening, prognostic, monitoring, pharmacogenomic and theranostic-from their basic principles to their applications.

• Discovering growing market opportunities by identifying high-growth applications in different cancer diagnostic areas, focusing on the biggest and expanding markets in oncology (e.g., biomarkers for breast cancer and predictive biomarkers).

• Focusing on global industry development through an in-depth analysis of the major world markets for cancer diagnostics, including growth forecasts.

This analysis emphasizes companies that are actively developing and marketing new reagents and supplies for performing cancer biomarker diagnostics tests. It discusses the various market trends and opportunities using new biomarkers, while providing an in-depth analysis of market share, revenue forecasts, and market drivers and restraints. The comprehensive focus of the study, backed by strategic recommendations, enables companies to position their growth strategies to benefit from the changing market conditions and obtain maximum return on investment.

This study surveys biotech companies known for marketing, manufacturing or developing instruments and reagents for the clinical cancer diagnostics market, both in the U.S. and the world. Leading companies are discussed in-depth, with sections on the companies’ histories, product lines, business and marketing analyses, and subjective commentary on the companies’ market positions.

This report answers the questions:

• Which companies are utilizing cutting-edge technologies to develop, validate, and implement cancer biomarkers for clinical use?
• What impediments still exist to incorporating promising research into clinical practice?
• Which cancer biomarkers show the most promise for approval?
• What are the economic challenges to approval?
• How can regulatory oversight drive approval and adoption of new technologies?
• Which alliances show the greatest synergy in bringing valid biomarkers to market?
• Which shared technologies are driving the most encouraging development?

Table of Contents

1. Overview 12
1.1 Statement of Report 12
1.2 About This Report 12
1.3 Scope of the Report 12
1.4 Objectives 13
1.5 Methodology 14
1.6 Executive Summary 15

2. Introduction to Cancer Biology and the Diagnostic Industry 17
2.1 Biomarkers 17
2.1.1 The Biomarker Market Drivers 17
2.1.1.1 The Sector 17
2.1.1.2 The Critical Path Opportunities 17
2.1.1.3 The Capital Markets 17
2.2 Cancer Detection and Treatment with Biomarkers 18
2.2.1 The Problem 19
2.3 Cancer: The Disease 21
2.3.1 Metastasis 21
2.3.2 Demographics and Statistics of Cancer 22
2.4 Drivers of the Biotech and Diagnostics Industry 28
2.4.1 Venture Funding of Biotech Sector 29
2.4.2 Technological Innovation 30
2.4.3 Government Funding 30
2.4.4 Pharmaceutical Development and Bioanalytical Services 30
2.4.5 The War on Cancer 32
2.4.6 Current Oncology Drug Development 32
2.5 Outlook for Tumor Markers 32
2.6 Focus on Proteomics 35
2.6.1 Scientific Background 35
2.6.2 The Relationship between Proteins and Diseases 35
2.6.3 Limitations of Existing Diagnostic Approaches 36
2.6.4 Addressing the Heterogeneity of Cancer 36
2.6.5 Validation of Biomarkers through Proper Study Design 37
2.6.6 Exploiting the Power of Mass Spectrometry to Improve Assay Specificity 37
2.6.7 Creating and Maintaining a Multi-Disease Product Pipeline 39
2.6.8 Partnerships for Developing Proteomic Biomarkers 39
2.7 Epigenic Markers for Cancer 40
2.8 Molecular Diagnostics Testing for Cancer 41
2.9 Market Opportunities 41
2.9.1 Industry Overview 42
2.9.2 Medical Indications and Medically Useful Information 44
2.9.3 Research Market 45
2.9.4 Competition 46
2.9.5 Diagnostic Services 46
2.9.6 Clinical Image Analysis 46
2.9.7 Research Imaging Market 46
2.9.8 Genomic Disease Management and In Vitro Diagnostic Multivariate Index Assays (IVDMIA) 47
2.9.9 Predictive Expression Profiles 48

3. Market Analysis of the Cancer Biomarkers Space 49
3.1 Scope of this Chapter 49
3.2 The Overall Market Opportunity and Segmentation of the Total Cancer Biomarkers Marketplace 49
3.3 Potential Cancer Biomarker Commercial Applications 52
3.3.1 Market for Routine Tumor Markers 53
3.3.2 Market for Genomic Cancer Biomarkers 58
3.3.3 Market Size and Forecasts for Companion Diagnostic Tests for Cancer Therapeutics 60
3.3.4 SWOT Analysis of the Major Cancer Biomarker Market Segments 62
3.3.4.1 Traditional Serum Cancer Biomarkers 62
3.3.4.2 Proteomic Cancer Biomarkers 63
3.3.4.3 Companion Diagnostic Cancer Biomarkers 64
3.4 Cancer Biomarker Market Estimates by Tissue of Origin 65
3.4.1 Colorectal 65
3.4.2 Prostate 66
3.4.3 Lung 66
3.4.4 Breast 66
3.4.5 Ovarian 67
3.5 Challenges Facing Cancer Biomarker Developers 67
3.6 Unmet Product Needs in the Cancer Biomarkers Space 69
3.7 Competitive Landscape of the Cancer Biomarkers Marketplace 71

4. Major Clinical Applications of Cancer Biomarkers 74
4.1 Launched Products and Pipeline 74
4.2 CYP2C9 Pharmacogenetics and Role in Personalized Medicine 76
4.3 Personalized Breast Cancer Therapy 76
4.4 Personalized NSCLC Therapy 77
4.5 AmpliChip®-based Personalized Medicine 77

5. Breast Cancer 78
5.1 Overview of Breast Cancer Disease 78
5.2 BRCA1 and BRCA2 Genes 79
5.2.1 Types of Genetic Testing Available for Breast Cancer 81
5.2.1.1 DNA Sequencing 81
5.2.1.2 Multi-Site Analysis 82
5.2.1.3 Single-Site Analysis 82
5.2.2 BRCA Test Results 82
5.2.2.1 What Does a Positive BRCA1 or BRCA2 Test Result Mean? 82
5.2.2.2 What Does a Negative BRCA1 or BRCA2 Test Result Mean? 82
5.2.2.3 What Does an Ambiguous BRCA1 or BRCA2 Test Result Mean? 83
5.2.2.4 What are the Options for a Person Who Tests Positive? 83
5.2.3 What are Some of the Benefits of Genetic Testing for Breast Cancer Risk? 84
5.2.4 What Are Some of the Risks of Genetic Testing for Breast and Ovarian Cancer Risk? 84
5.3 Estrogen Receptors and Breast Cancer 84
5.3.1 Expression and Prognostic Value of ER 84
5.3.2 Progesterone Receptors and Breast Cancer 85
5.3.3 ER and PR Predict Response to Endocrine Therapy 85
5.4 HER2 Gene and Protein 86
5.4.1 HER2 Tests 86
5.4.1.1 IHC Test 86
5.4.1.2 FISH Test 87
5.4.1.3 Questions About Testing 89
5.4.1.4 HER2 Tumor Status 90
5.5 Herceptin® Treatment 90
5.6 Tumor Assays for Adjuvant Chemotherapy 92
5.7 Use of Genomics to Understand Breast Cancer 93
5.8 Genetic Analysis Solution 94
5.8.1 The Use of Proteomics in Breast Cancer 95
5.8.2 Tissue Microarrays 96
5.8.3 Protein Microarrays 98
5.9 Gene Expression Microarrays and Recurrence Prediction 99
5.9.1 Oncotype DX 100
5.9.2 Oncotype DX for Breast Cancer 101
5.9.3 Risk Assessment 101
5.9.4 Use of Chemotherapy 101
5.9.5 Utility of the Oncotype Test 101
5.9.6 Clinical Development and Validation of Oncotype DX 102
5.9.6.1 Clinical Development of the Oncotype DX Recurrence Score 102
5.9.6.2 Clinical Validation of Prediction of Recurrence and Survival in N−, ER+ Patients Treated with Tamoxifen 102
5.9.6.3 Oncotype DX Predicts the Likelihood of Recurrence 103
5.9.6.4 Oncotype DX Predicts the Likelihood of Breast Cancer Survival in a Community Hospital Setting 103
5.9.6.5 Oncotype DX Predicts both Prognosis and Tamoxifen Benefit 104
5.10 Economic Benefits of Oncotype DX 104
5.11 Increased Clinical Utility of Oncotype DX 105
5.12 Second Generation Oncotype DX 106
5.12.1 Recurrence and Benefit Test for N−, ER− Breast Cancer 106
5.12.2 Taxane Benefit Test 106
5.13 MammaPrint 106
5.14 Rotterdam Signature 76-Panel 107
5.15 Summary of Microarray Technologies 107
5.16 Mass Spectrometry-based Approaches 108
5.16.1 Gel-based Approaches 108
5.16.2 Non-Gel-based Approaches 109
5.16.2.1 SELDI-TOF MS 109
5.16.2.2 SELDI and Prognosis 110
5.16.2.3 SELDI and Treatment Monitoring 111
5.16.3 Limitations of Mass Spectroscopy 111
5.17 Outlook 112
5.18 Future Perspectives 114
5.19 Breast Cancer Program (NMP66) 115
5.20 Myriad Genetics 115
5.21 Veridex GeneSearch™ Breast Lymph Node 116
5.22 OncoVue Cancer Risk Test 116
5.23 Research Biomarkers for Breast Cancer 116
5.24 Protein Biomarkers for Breast Cancer Prevention 117
5.25 Biomarker Prognosis of Breast Cancer Treated with Doxorubicin 117

6. Ovarian Cancer118
6.1 Serum Markers 120
6.2 Biomarkers 121
6.2.1 Strategies for Discovering New Cancer Biomarkers 122
6.3 Serum Protein Biomarkers for Ovarian Cancer 122
6.3.1 Clinical Proteomics 123
6.4 Ovarian Cancer Triage Testing 124
6.4.1 Vermillion’s Ovarian Cancer Triage Diagnostic Program 125

7. Prostate Cancer 127
7.1 Overview 127
7.1.1 Prevalence 127
7.1.2 Prostate Cancer Progression and Recurrence Test 127
7.1.3 Current Market Size 127
7.2 Genes Involved in Prostate Cancer 128
7.3 Androgen Independence 129
7.4 Gene Markers in Prostate Cancer 130
7.5 Microarray Gene Identification of Prostate Biomarkers 130
7.6 GEArray DNA Microarrays 132
7.7 Vermillion’s Cancer Diagnostic Program 133
7.8 Hepsin 133
7.9 Matritech’s Prostate Cancer Program (NMP48) 133
7.10 Gen-Probe’s PCA3 Assay 134
7.11 Early Prostate Cancer Antigen-2 (EPCA-2) 134
7.12 Mass Spectrometry 135
7.13 Summary 137

8. Bladder Cancer 138
8.1 Overview 138
8.1.1 Prevalence 138
8.1.2 Progression and Recurrence 138
8.1.3 Bladder Cancer Risk Factors 138
8.1.4 Bladder Cancer Symptoms 138
8.2 Bladder Cancer Tests 138
8.3 UroVysion Bladder Cancer Kit 139
8.4 Ikoniscope® Robotic Digital Microscopy Platform 140
8.4.1 The CellOptics Platform 140
8.4.2 Cell Staining and Genetic Characterization 140
8.4.3 Ikoniscope/IkoniLAN Automated Microscopy 140
8.5 Nuclear Matrix Protein Markers 141
8.6 ImmunoCyt™/uCyt+™ 143
8.7 Cangen Microsatellite DNA 145
8.8 Bladder Cancer Market 145
8.8.1 Urologist Market 145
8.8.2 Clinical Lab Market 145
8.8.3 Primary Care Market 145
8.8.4 Private and Public Sector Markets 146
8.8.5 POC Market 146
8.8.6 Market Distribution 146
8.8.7 Reimbursement 146

9. Colorectal Cancer 147
9.1 Overview 147
9.1.1 Prevalence 147
9.1.2 Progression and Recurrence 147
9.2 Screening for CRC 149
9.2.1 Stool-based DNA (sDNA) Screening 150
9.3 Almac Diagnostics DSA 151
9.4 Colon Cancer Program (NMP35) 152
9.5 Myriad Genetics Colaris AP Risk Assessment 152
9.6 Summary 153

10. Genetic Diagnostics Set to Revolutionize Cancer Diagnostic Testing 154
10.1 Overview 154
10.1.1 Clinicians Need for More Information with Regard to Therapeutic Treatment Drives Demand for Pharmacogenomic Testing 154
10.1.2 Predictive Medicine Shows Potential for Genetic Diagnostics 154
10.1.3 Different Rates of Growth 155
10.1.4 Effective Competitive Strategies 155
10.1.5 Improvements in Marketing Effectiveness 155
10.1.6 Emerging Technologies Imply Start of a New Era and Offer Tremendous Growth Opportunities 155
10.1.7 Increased Market Share 155
10.1.8 Technologies Used in Genetic Testing 155
10.2 AMAS Test 156
10.3 Corixa Antibodies as Tumor Markers 156
10.4 Cytovision 157
10.5 Ariol System 157
10.6 Mammaglobin Protein Expression 157
10.7 L523S or KOC RNA Binding Protein 157
10.8 CA1-18 from EDP Biotech 158

11. Leukemia Biomarkers 159
11.1 Overview 159
11.1.1 Prevalence 159
11.1.1.1 Progression and Recurrence 159

12. Lung Cancer 160

13. Enabling Technologies for Oncology Biomarker Discovery 161
13.1 Automated Cellular Imaging System (ACIS®) 161
13.1.1 ACIS for HER2 Protein Expression Testing 162
13.1.2 ACIS for ER Protein Expression Testing 162
13.1.3 ACIS for PR Protein Expression Testing 162
13.1.4 ACIS for Cell Proliferation Expression 163
13.1.5 ACIS for Protein Expression 163
13.1.6 ACIS for Protein Micrometastases in Bone Marrow 163
13.1.7 ACIS for Protein Micrometastases in Tissue 163
13.1.8 ACIS for Tissue Microarray 163
13.1.9 ACIS for DNA Ploidy 163
13.1.10 ACIS for HPV 163
13.2 DNA Methylation 164
13.2.1 Differential Methylation Hybridization (DMH) 164
13.2.2 MIRA-Assisted Microarrays for DNA Methylation Analysis and Cancer Diagnosis 164
13.3 Proteomics 165
13.3.1 Proteomics Technologies for Cancer Marker Discovery 165
13.3.2 Validation of Candidate Biomarkers 166
13.3.3 Requirements Bringing a New Marker into the Market 166
13.3.4 Value Chain in the Development of New Cancer Biomarkers 167
13.4 Secreted Proteins as Cancer Biomarkers 167
13.4.1 Markers of Known Tissue Origin 167
13.4.2 Secreted Proteins as Low Abundance Markers 167
13.4.3 Secreted Proteins in Tissue and Blood 167
13.5 Noncodings RNA as Potential Tumor Markers 167
13.5.1 miRNA Meets Microarray 168
13.5.2 Mimetics and Inhibitors 168
13.5.3 Clinical Patterns in Cancer 168
13.6 Architect TIMP-1 (Tissue Inhibitor of Metalloproteinases-1) Immunoassay for Colorectal Cancer Detection 168
13.7 Companies Developing Automated Microscope-based Analysis Systems 168
13.8 Companies Developing Research Products for Tumor Cell Isolation 169
13.9 Companies Supplying Fluorescently Labeled Antibodies to Characterize Tumor Cells 169
13.10 PerkinElmer High Throughput Platforms: AlphaScreen®, AequoScreen®, DELFIA® and LANCE® Technologies 169

14. Biomarker Tests Co-developed with Cancer Therapeutics as Companion Diagnostics 169
14.1 Sector Overview 170
14.2 Companion Diagnostics 171
14.3 EGFR for Colorectal Cancer and Camptostar (Irinotecan) 172
14.4 EGFR Express and Erbitux (Cetuximab) 172
14.5 HER2 and Heceptin 173
14.6 Myriad’s TheraGuide 5-FU 173
14.7 TheraScreen: EGFR29 173
14.8 Drivers and Barriers to Companion Diagnostics 174
14.9 Partnerships with Pharma Companies to Identify Therapeutic Targets 175
14.10 Future Developments for Companion Diagnostics 175

15. Companion Diagnostics and Personalized Medicine: Biology, Approaches, Pipeline and Regulatory Trends 177
15.1 Scope of this Chapter 177
15.2 Introduction to Companion Diagnostics and Personalized Medicine 177
15.3 The Compelling Case for Personalized Medicine 179
15.4 Drug Metabolism and Implications for Companion Diagnostics and Personalized Medicine 180
15.5 Examples of Personalized Medicine 184
15.6 Personalized Medicine and Companion Diagnostics Testing Product Pipeline 186
15.7 The Personalized Medicine Coalition 188
15.8 Regulatory Trends and Guidelines in the Personalized Medicine Space 190
15.8.1 The Changing Regulatory Landscape for Personalized Medicine 192
15.9 Patenting Personalized Medicine 193
15.10 The Leading Edge of Personalized Medicine: Specific Examples of Clinical Situations Where Personalized Medicine and Companion Diagnostics is Appropriate and Being Deployed 195
15.10.1 EGFR Assay 195
15.10.2 Individualized Warfarin Therapy 196
15.10.3 UGT1A1 Molecular Assay for Camptosar 197
15.10.4 Response to Gleevec in Gastrointestinal Stromal Tumors 197
15.10.5 LabCorp, ARCA Personalized Medicine Deal for Cardiovascular Diseases 197
15.10.6 Osmetech Licenses Epidauros Biotechnologie AG CYP2D6 Biomarker to Push into Companion Diagnostics 198
15.11 Companion Diagnostics and Personalized Medicine: Qualitative and Quantitative Market Analysis 198
15.11.1 Market Analysis of Molecular Diagnostics and Companion Diagnostics and Personalized Medicine 198
15.11.2 Diagnostics vs. Pharmaceuticals 199
15.11.3 Molecular Diagnostic Market 200
15.11.4 Molecular Diagnostics Technology Platforms and their Impact on Personalized Medicine 202
15.12 Snapshot of Companion Diagnostics Industry Structure 204
15.13 The Case for Theranostics (Therapeutic/Companion Diagnostic) 205
15.14 Personalized Medicine Market Analysis-Market Survey Data Characterizing the Qualitative and Quantitative Industry Parameters 206
15.15 How the Market Segregates Today 207
15.16 Timeline for Impact of Various Segments in Personalized Medicine 208
15.17 Challenges for Personalized Therapeutics and Companion Diagnostics Development 210
15.18 Macro Trends in Personalized Medicine 210
15.19 Personalized Medicine and Companion Diagnostics: Industry SWOT Analysis 214

16. Cancer Biomarker Testing Sector and Company Analysis 216
16.1 Abbott Molecular, Inc. (Formerly Vysis, Inc.) 216
16.2 Agendia 218
16.3 AMDL, Inc. 218
16.4 Aureon Laboratories, Inc. 218
16.5 BioCurex 218
16.6 Biomarker Technologies 218
16.7 Biomedical Diagnostics LLC 218
16.8 Biomerica 219
16.9 Biomira, Inc. 219
16.10 Biomoda 219
16.11 Byk Gulden 219
16.12 Clarient 220
16.13 Correlogic Systems, Inc. 221
16.14 Cytogen Corporation 221
16.15 Dako (Formerly Dako Cytomation) 222
16.16 diaDexus 223
16.17 Diagnocure, Inc. (ImmunoCyt™/uCyt+™) 223
16.18 DxS Ltd. 224
16.19 Epigenomics 225
16.20 Exagen Diagnostics, Inc. 226
16.21 Genesis Genomics 227
16.22 Health Discovery Corporation 227
16.23 Immunicon 227
16.24 Ipsogen 228
16.25 InterGenetics 229
16.26 Miraculins, Inc. 230
16.27 Molecular Devices Inc. (Formerly Arcturus Bioscience, Inc.) 230
16.28 Myriad Genetics, Inc. 230
16.29 Orion Genomics 231
16.30 Power3 Medical Products 231
16.31 Qiagen N.V. 232
16.32 SuperArray Bioscience Corporation 232
16.33 Upstream Biosciences, Inc. 232
16.34 Ventana Medical Systems, Inc. 233
16.35 Veridex 233
16.36 Vermillion 234

17. Business Trends in the Industry 238
17.1 Industry Consolidation 238
17.2 Breath of Product Offering and Pricing 239
17.3 Government Regulation of Medical Devices 239
17.3.1 FDA Guidance on Drug Test Co-development 241
17.4 Strategic Business and Marketing Considerations 241
17.5 Commercial Opportunities in Cancer Markers 241
17.5.1 Licensing and Intellectual Property (IP) Constraints and how they will Impact New Product Development 242
17.6 Moderators of Growth 242
17.6.1 Roadblocks to Integrating Cancer Biomarkers into Clinical Practice 243
17.7 Biotechnology Industry Trends 243
17.8 Pharmaceutical Industry Trends 244
17.9 Acquisition, License Agreement, Partnerships 245
17.10 Legal Developments 248
17.11 Sales and Marketing Strategies for Tumor Marker Tests 249
17.11.1 North American Market 250
17.11.2 International Markets 251
17.11.2.1 Europe 251
17.11.2.2 Central and South America 252
17.11.2.3 Asia/Pacific 252
17.12 Product Commercialization 252
17.13 Reimbursement 253
17.14 Self Referral Rules 254
17.15 Health Insurance Portability and Accountability Act 255
17.16 Clinical Laboratory Improvement Amendments (CLIA) 255
17.17 In-Vitro Diagnostic Directive (IVDD) and Medical Device Regulations 256
17.18 FDA’s Quality System Regulation (QSR) 257
17.19 FDA’s OIVD on IVDMIAs 257
17.20 FDA’s Qualification of Cancer Biomarkers 258
17.20.1 Regulatory Perspectives of Biomarker Validation 258
17.21 Genetic Tests and Medical Records 258
17.21.1 Laws against Genetic Discrimination 259
17.22 Medicare Reimbursement 260
17.22.1 Medicare Part B Spending Trends 260
17.23 Global Drivers of Clinical Laboratory Testing 262
17.24 Global Outlook for Cancer Biomarkers 262
17.24.1 Which Companies are Utilizing Cutting-Edge Technologies to Develop, Validate and Implement Cancer Biomarkers for Clinical Use? 263
17.24.2 What Impediments Still Exist to Incorporating Promising Research into Clinical Practice? 263
17.24.3 Which Biomarkers Show the Most Promise for Approval? 264
17.24.4 How can Regulatory Oversight Drive Approval and Adoption of New Technologies? 264
17.24.5 Which Alliances Show the Greatest Synergy in Bringing Valid Biomarkers to Market? 264
17.24.6 Which Shared Technologies are Driving the Most Encouraging Development? 264
17.24.7 How Strategic Alliances and Interdisciplinary Involvement Drive Development and Implementation of Emerging Biomarker Technologies 265
17.25 Oncology Biomarker Qualification Initiative 265
17.26 FDA Critical Path 266
17.27 FDA Criteria for a Valid Biomarker 266

18. Companies Entering the Cancer Diagnostics Market with Novel Technology Platforms 267
18.1 Abbott Diagnostics 267
18.2 Affymetrix, Inc. 269
18.3 Agendia BV 271
18.4 Agensys, Inc. 272
18.5 Almac Group 272
18.6 AMDL, Inc. 272
18.7 Aureon Laboratories, Inc. 274
18.8 Bayer Diagnostics Corporation 275
18.9 Beckman Coulter, Inc. 275
18.10 Biocode S.A. 276
18.11 BioCurex, Inc. 277
18.12 Biomarker Technologies LLC 277
18.13 Biomedical Diagnostics LLC 277
18.14 Biomerica 277
18.15 bioMérieux 278
18.16 Biomira, Inc. 278
18.17 Biomoda, Inc. 279
18.18 Bruker Daltonics, Inc. 280
18.19 Byk Gulden 280
18.20 Cangen Biotechnologies, Inc. 280
18.21 Caprion Proteomics 282
18.22 Celera Diagnostics 282
18.23 Cepheid 283
18.24 Clarient, Inc. 284
18.25 Claros Diagnostics, Inc. 285
18.26 Clinical Data, Inc.: PGxHealth and Cogenics 285
18.27 Correlogic Systems, Inc. 286
18.28 CytoCore (Formerly Molecular Diagnostics, Inc.) 287
18.29 Cytogen Corporation 287
18.30 Dako (Formerly Dako Cytomation) 290
18.31 diaDexus LLC 291
18.32 DiagnoCure, Inc. 292
18.33 Diagnostic Products Corporation 293
18.34 Diagnostic Systems Laboratories, Inc. 293
18.35 Digene Corporation 293
18.36 DRG International, Inc. 294
18.37 DxS Ltd. 294
18.38 EDP Biotech Corporation 295
18.39 Eisai Co., Ltd. 296
18.40 Epigenomics 296
18.41 Exact Sciences Corporation 297
18.42 Exagen Diagnostics, Inc. 297
18.43 Gene Logic, Inc. 298
18.44 Genesis Genomics, Inc. 299
18.45 Genomic Health, Inc. 299
18.46 Gen-Probe, Inc. 299
18.47 Health Discovery Corporation 300
18.48 Hologic, Inc. (Formerly Cytyc Corporation) 301
18.49 Ikonisys, Inc. 301
18.50 Immunicon Corporation 302
18.51 Immunomedics, Inc. 306
18.52 Incyte Pharmaceuticals, Inc. 307
18.53 InterGenetics® 307
18.54 Ipsogen 307
18.55 LabCorp® 308
18.56 Matritech, Inc. 309
18.57 Miraculins, Inc. 311
18.58 Mitsubishi Kagaku Medical 312
18.59 Molecular Devices (Formerly Arcturus Biosciences, Inc.) 312
18.60 Myriad Genetics, Inc. 312
18.61 NimbleGen Systems, Inc. 317
18.62 Northwest Biotherapeutics, Inc. 317
18.63 Oncotech, Inc. 318
18.64 Orion Genomics 319
18.65 Oxford Genome Sciences 319
18.66 Panacea Pharmaceuticals, Inc. 320
18.67 Phenomenone Discoveries 320
18.68 Polymedco, Inc. 320
18.69 Power3 Medical Products 321
18.70 Proteome Systems Ltd. 321
18.71 Qiagen N.V. 322
18.72 Sanko Junyaku Co., Ltd. 323
18.73 SensiGen LLC 323
18.74 SuperArray Bioscience Corporation 323
18.75 Third Wave Technologies, Inc. 323
18.76 Tosoh Medics, Inc. 324
18.77 TriPath Imaging, Inc. 324
18.78 Upstream Biosciences, Inc. 326
18.79 Ventana Medical Systems, Inc. 326
18.80 Veridex LLC 327
18.81 Vermillion, Inc. (Formerly Ciphergen) 328

Appendix 1: Cancer Biomarker Centers of Research 331
Appendix 2: Myriad Patents on Genes BRAC1 and BRAC2 332
Appendix 3: Common Laboratory Tests for Cancer 333
Appendix 4: Questions/Issues in the Cancer Biomarkers Space 340
Appendix 5: Cancer Markers Currently in Common Clinical Use 342
Appendix 6: International Federation of Gynecology and Obstetrics (FIGO) Staging System for Primary Carcinoma of the Ovary 343
Appendix 7: FDA Guidance for Industry: Pharmacogenomic Data Submission 344

A7.1 Introduction 344
A7.2 Background 344
A7.3 Submission Policy 345
A7.3.1 General Principles 345
A7.3.2 Specific Uses of Pharmacogenomic Data in Drug Development and Labeling 347
A7.3.3 Benefits of Voluntary Submissions to Sponsors and FDA 348
A7.4 Submission of Pharmacogenomic Data 349
A7.4.1 Submission of Pharmacogenomic Data During the IND Phase 349
A7.4.2 Submission of Pharmacogenomic Data to a New NDA, BLA, or Supplement 350
A7.4.3 Submission to a Previously Approved NDA or BLA 351
A7.4.4 Compliance with 21 CFR Part 58 351
A7.4.5 Submission of Voluntary Genomic Data from Application-Independent Research 352
A7.5 Format and Content of a VGDS 352
A7.6 Process for Submitting Pharmacogenomic Data 353
A7.7 Agency Review of VGDSs 353
Glossary 355

INDEX OF FIGURES
Figure 3.1: Potential Market for Cancer Biomarkers, 2006 49
Figure 3.2: Segmentation of the Cancer biomarkers Marketplace Based Upon Commercial Offerings-Products and Services 52
Figure 3.3: Geographical Distribution of Cancer Tumor Diagnostic Testing 56
Figure 3.4: Cancer Biomarkers Research Market, 2006-2011 61
Figure 3.5: Breast Cancer Biomarker Market Potential, 2005 67
Figure 3.6: Challenges in the Study or Utilization of Proteomic Cancer Biomarkers 68
Figure 3.7: Challenges in the Study or Utilization of Companion Diagnostic Cancer Biomarkers 68
Figure 3.8: Challenges in the Study or Utilization of Serum Cancer Markers 69
Figure 3.9: Top Unmet Needs in Commercial Products in the Cancer Biomarkers Space 70
Figure 5.1: Hybridization Process 87
Figure 5.2: FISH Test Procedure 88
Figure 5.3: Gene Expression Profiling 98
Figure 15.1: Phase I and II Processes of Drug Metabolism 180
Figure 15.2: Human Phase I Enzymes 181
Figure 15.3: Human Phase II Enzymes 181
Figure 15.4: Hepatic Distribution of Human CYP450 182
Figure 15.5: Relative Contribution of CYP450 Enzymes to Drug Metabolism 182
Figure 15.6: Genetic Components Determine Drug Metabolism 183
Figure 15.7: From Genetic Content to Personalized Medicine 199
Figure 15.8: Remuneration for Diagnostics 199
Figure 15.9: Breakout of the Molecular Diagnostics Marketplace 200
Figure 15.10: Molecular Diagnostics Market Segmentation 201
Figure 15.11: Molecular Diagnostics Market Segmentation by Technology 202
Figure 15.12: Market Survey Respondent Demographics 206
Figure 15.13: Breakout of the Respondent Pool by Affiliation 207
Figure 15.14: Segmentation of the Personalized Medicine Market 207
Figure 15.15: Personalized Medicine Market Drivers 211
Figure 15.16: Challenges in the Personalized Medicine Space 212
Figure 16.1: Epigenomics Product Development Pipeline 226
Figure 17.1: Medicare Part B Spending on Clinical Laboratory Services, 1991-2005 260

INDEX OF TABLES
Table 2.1: Cancer Biomarkers at the Nexus Point 19
Table 2.2: Drug Development by Type of Cancer 22
Table 2.3: Organ Specific Medicines in Development for Cancer, 2006 23
Table 2.4: Estimates for the Leading Sites of New Cancer Cases and Deaths in the U.S. by Sex, 2007 24
Table 2.5: Estimated Worldwide Number of New Cancer Cases and Deaths by Type of Cancer 24
Table 2.6: Estimated Number of New Cancer Cases and Deaths by Region 25
Table 2.7: Cancer Death Rates per 100,000 Population (and Rank) for All Cancer Sites by Country 26
Table 2.8: Cancer Associated Genes 27
Table 2.9: Carcinogens in the Workplace 27
Table 2.10: Cancer Biomarker Markets 28
Table 2.11: Private Funding Levels for the Biotechnology Segment, 1995-2006 29
Table 2.12: Global Pharmaceutical Industry R&D Spending, 1995-2006 31
Table 2.13: U.S. Government NIH Research Budget, 1995-2007 31
Table 2.14: Tumor Markers Currently in Common Use 33
Table 2.15: Herceptin Worldwide Sales, 1999-2006 34
Table 2.16: Classes of Drugs Used to Treat Breast Cancer 34
Table 2.17: Solutions to Biomarker Developments 36
Table 2.18: Vermillion Collaborations 39
Table 2.19: Uses of Molecular Diagnostics in Detection and Management of Cancer 41
Table 2.20: U.S. Cancer Diagnostic Testing Market Size, 2005-2012 43
Table 2.21: Breath of Cancer Biomarker Market by Stage of Test 43
Table 2.22: Market Opportunities for Cancer Biomarker Technology Platforms 44
Table 3.1: Characteristics of Different Cancer Biomarker Types and Associated Market Opportunities 51
Table 3.2: Segmentation of the Cancer Biomarker Market by Type/Lineage of Cancer Biomarkers and Market Size 51
Table 3.3: In Vitro Cancer Marker Market Segments Worldwide, 2001 and 2007 53
Table 3.4: Worldwide Market Size in Dollar Volume for Tumor Marker Assays Product Market, 2001-2010 53
Table 3.5: U.S. Market Size in Dollar Volume for Tumor Marker Assays Product Market, 2001-2010 54
Table 3.6: Worldwide In Vitro Cancer Tumor Marker Diagnostics Market Size, 2001-2010 54
Table 3.7: U.S. In Vitro Cancer Tumor Marker Diagnostics Market Size, 2001-2010 54
Table 3.8: Japanese In Vitro Cancer Tumor Marker Diagnostics Market Size, 2001-2010 55
Table 3.9: European In Vitro Cancer Tumor Marker Diagnostics Market Size, 2001-2010 55
Table 3.10: Global Distribution of IVD Cancer Tumor Marker Diagnostic Testing, 2005 55
Table 3.11: Estimated Market Share of Major Competitors in U.S. Cancer Tumor Marker Diagnostics Market 56
Table 3.12: Major Presence in Cancer Tumor Marker Diagnostics Markets 56
Table 3.13: Worldwide CEA Sales, 2001-2010 57
Table 3.14: U.S. CEA Sales, 2001-2010 58
Table 3.15: Cancer Genomic Biomarker Markets, 2002-2012 58
Table 3.16: Cancer Biomarkers Research Market Forecast, 2006-2011 61
Table 3.17: Cancer Biomarker Market Estimates by Tissue of Origin 65
Table 3.18: Companies Developing New Proteomic Cancer Biomarker Technology Platforms 73
Table 4.1: Cancer Biomarkers Used to Maximize Likelihood of Response 75
Table 4.2: Biomarkers for Monitoring Therapeutic Effectiveness and Resistance 75
Table 4.3: Biomarkers for Dose Response of Therapy 75
Table 4.4: Decision on Optimal Duration of Therapy 75
Table 5.1: U.S. Breast Cancer Rate Decline, 2002-2006 78
Table 5.2: BRCA Development Model 80
Table 5.3: BRCA Test Development and Commercialization 81
Table 5.4: BRAC Analysis 81
Table 5.5: Revenue for BRACAnalysis® Risk Assessment Test, 2002-2006 81
Table 5.6: GEArray DNA Microarrays and RT2 Profiler PCR Arrays 98
Table 5.7: Product Development Opportunities in Breast Cancer 105
Table 5.8: Concentration of Some Abundant Proteins, New Cancer Biomarkers Identified by SELDI-TOF, and Classical Cancer Biomarkers in Serum 112
Table 5.9: Questions Related to Diagnostic SELDI-TOF Technology 114
Table 6.1: Worldwide CA-125 Sales, 2001-2010 118
Table 6.2: U.S. CA-125 Sales, 2001-2010 119
Table 6.3: Some Clinically Established Cancer Serum Markers Currently in Use for Cancer 120
Table 6.4: Pathophysiology of Ovarian Cancer and Characterization of Ovarian Epithelial Tumors 126
Table 7.1: Worldwide PSA Sales, 2000-2010 128
Table 7.2: U.S. PSA Sales, 2000-2010 128
Table 7.3: Molecular Gene Markers for Prostate Cancer 130
Table 8.1: Worldwide Bladder Cancer Marker Sales, 2001-2010 142
Table 8.2: U.S. Bladder Cancer Marker Sales, 2001-2010 142
Table 8.3: Worldwide NMP22 Sales, 2001-2010 143
Table 8.4: Summary of Matritech’s Product Development Programs 144
Table 8.5: Opportunities for Bladder Cancer Biomarkers 145
Table 9.1: TNM Staging for Colorectal Cancer 148
Table 10.1: Genetic Diagnostics Market, 2004-2012 154
Table 13.1: Genomic and Proteomic Technologies 166
Table 14.1: Potential Benefits of Biomarkers as Companion Diagnostics 172
Table 14.2: Utility of Biomarker as Companion Diagnostics to Drug Development 172
Table 14.3: Device Submission Elements for the FDA 174
Table 14.4: Summary of Biomarker Use in the Commercialization of Novel Oncology Pharmacotherapeutics 176
Table 14.5: Pharmacoeconomic Challenges to the Implementation of Biomarkers as Companion Diagnostic Tests 176
Table 15.1: Percentage of Non-Responders in Various Drug Classes 179
Table 15.2: High Profile Drug Withdrawals from the Marketplace 179
Table 15.3: Drug Metabolism Drives Drug Efficacy/Toxicity 184
Table 15.4: Population Frequency of the Various Cytochromes 184
Table 15.5: Selected List of Personalized Medicine Tests 185
Table 15.6: Personalized Medicine and Companion Diagnostics Product Pipeline 186
Table 15.7: Marketed Personalized Therapies, 2006 187
Table 15.8: Various Molecular Diagnostics Technologies: Timeline for Impact 202
Table 15.9: Various Molecular Diagnostics Technologies: Impact on Different Therapeutic Areas in Personalized Medicine 203
Table 15.10: Various Molecular Diagnostics Technologies: Technical Challenges in the Deployment for Personalized Medicine 203
Table 15.11: Classification of Diagnostics by Risk 205
Table 15.12: Areas in Personalized Medicine-Timeline of Impact 208
Table 15.13: Impact of Personalized Medicine on Various Therapeutic Areas 209
Table 15.14: Hurdles in Personalized Medicine and Companion Diagnostics Development in Various Therapeutic Areas 210
Table 15.15: Market Opportunities in Personalized Medicine 213
Table 15.16: Challenges for Market Adoption of the Various Personalized Medicine Tests 214
Table 15.17: Personalized Medicine Industry SWOT 215
Table 16.2: Clarient Revenue, 2002-2006 220
Table 16.3: Clarient Percentage of Revenue, 2004-2006 220
Table 16.1: Opportunities for Biomarkers in Cancer Diagnosis and Treatment 221
Table 16.4: Myriad Biomarker Revenue, 2002-2006 231
Table 17.1: List and Discounted Prices for Abbott Tumor Marker Tests 239
Table 17.2: Hospital Laboratory Share of Part B Medicare Spending, 1996-2005 260
Table 17.3: Medicare Spending on Clinical Lab Services, 1991-2005 261
Table 17.4: Medicare Part B Spending Per Medicare Enrollee, 1998-2005 261
Table 18.1: Tumor Diagnosis Immunoassay 294
Table 18.2: Tumor Diagnosis Radioimmunoassay 294
Table 18.3: Summary of Matritech’s Product Development Programs 311
Table A1: Team Descriptions 331
Table A5: Cancer Markers in Use 342