Biomarker Technology Platforms for Cancer Diagnoses and Therapies - Market Research Reports

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) 46
2.9.9 Predictive Expression Profiles 47

3. Market Analysis of the Cancer Biomarkers Space 48
3.1 Scope of this Chapter 48
3.2 The Overall Market Opportunity and Segmentation of the Total Cancer Biomarkers Marketplace 48
3.3 Potential Cancer Biomarker Commercial Applications 51
3.3.1 Market for Routine Tumor Markers 52
3.3.2 Market for Genomic Cancer Biomarkers 57
3.3.3 Market Size and Forecasts for Companion Diagnostic Tests for Cancer Therapeutics 59
3.3.4 SWOT Analysis of the Major Cancer Biomarker Market Segments 61
3.3.4.1 Traditional Serum Cancer Biomarkers 61
3.3.4.2 Proteomic Cancer Biomarkers 62
3.3.4.3 Companion Diagnostic Cancer Biomarkers 63
3.4 Cancer Biomarker Market Estimates by Tissue of Origin 64
3.4.1 Colorectal 64
3.4.2 Prostate 65
3.4.3 Lung 65
3.4.4 Breast 65
3.4.5 Ovarian 66
3.5 Challenges Facing Cancer Biomarker Developers 66
3.6 Unmet Product Needs in the Cancer Biomarkers Space 68
3.7 Competitive Landscape of the Cancer Biomarkers Marketplace 70

4. Major Clinical Applications of Cancer Biomarkers 73
4.1 Launched Products and Pipeline 73
4.2 CYP2C9 Pharmacogenetics and Role in Personalized Medicine 75
4.3 Personalized Breast Cancer Therapy 75
4.4 Personalized NSCLC Therapy 76
4.5 AmpliChip®-based Personalized Medicine 76

5. Breast Cancer 77
5.1 Overview of Breast Cancer Disease 77
5.2 BRCA1 and BRCA2 Genes 78
5.2.1 Types of Genetic Testing Available for Breast Cancer 80
5.2.1.1 DNA Sequencing 80
5.2.1.2 Multi-Site Analysis 81
5.2.1.3 Single-Site Analysis 81
5.2.2 BRCA Test Results 81
5.2.2.1 What Does a Positive BRCA1 or BRCA2 Test Result Mean? 81
5.2.2.2 What Does a Negative BRCA1 or BRCA2 Test Result Mean? 81
5.2.2.3 What Does an Ambiguous BRCA1 or BRCA2 Test Result Mean? 82
5.2.2.4 What are the Options for a Person Who Tests Positive? 82
5.2.3 What are Some of the Benefits of Genetic Testing for Breast Cancer Risk? 83
5.2.4 What Are Some of the Risks of Genetic Testing for Breast and Ovarian Cancer Risk? 83
5.3 Estrogen Receptors and Breast Cancer 83
5.3.1 Expression and Prognostic Value of ER 83
5.3.2 Progesterone Receptors and Breast Cancer 84
5.3.3 ER and PR Predict Response to Endocrine Therapy 84
5.4 HER2 Gene and Protein 85
5.4.1 HER2 Tests 85
5.4.1.1 IHC Test 85
5.4.1.2 FISH Test 86
5.4.1.3 Questions About Testing 88
5.4.1.4 HER2 Tumor Status 89
5.5 Herceptin® Treatment 89
5.6 Tumor Assays for Adjuvant Chemotherapy 91
5.7 Use of Genomics to Understand Breast Cancer 92
5.8 Genetic Analysis Solution 93
5.8.1 The Use of Proteomics in Breast Cancer 94
5.8.2 Tissue Microarrays 95
5.8.3 Protein Microarrays 97
5.9 Gene Expression Microarrays and Recurrence Prediction 98
5.9.1 Oncotype DX 99
5.9.2 Oncotype DX for Breast Cancer 100
5.9.3 Risk Assessment 100
5.9.4 Use of Chemotherapy 100
5.9.5 Utility of the Oncotype Test 100
5.9.6 Clinical Development and Validation of Oncotype DX 101
5.9.6.1 Clinical Development of the Oncotype DX Recurrence Score 101
5.9.6.2 Clinical Validation of Prediction of Recurrence and Survival in N-, ER+ Patients Treated with Tamoxifen 101
5.9.6.3 Oncotype DX Predicts the Likelihood of Recurrence 102
5.9.6.4 Oncotype DX Predicts the Likelihood of Breast Cancer Survival in a Community Hospital Setting 102
5.9.6.5 Oncotype DX Predicts both Prognosis and Tamoxifen Benefit 103
5.10 Economic Benefits of Oncotype DX 103
5.11 Increased Clinical Utility of Oncotype DX 104
5.12 Second Generation Oncotype DX 105
5.12.1 Recurrence and Benefit Test for N-, ER- Breast Cancer 105
5.12.2 Taxane Benefit Test 105
5.13 MammaPrint 105
5.14 Rotterdam Signature 76-Panel 106
5.15 Summary of Microarray Technologies 106
5.16 Mass Spectrometry-based Approaches 107
5.16.1 Gel-based Approaches 107
5.16.2 Non-Gel-based Approaches 108
5.16.2.1 SELDI-TOF MS 108
5.16.2.2 SELDI and Prognosis 109
5.16.2.3 SELDI and Treatment Monitoring 110
5.16.3 Limitations of Mass Spectroscopy 110
5.17 Outlook 111
5.18 Future Perspectives 113
5.19 Breast Cancer Program (NMP66) 114
5.20 Myriad Genetics 114
5.21 Veridex GeneSearch™ Breast Lymph Node 115
5.22 OncoVue Cancer Risk Test 115
5.23 Research Biomarkers for Breast Cancer 115
5.24 Protein Biomarkers for Breast Cancer Prevention 116
5.25 Biomarker Prognosis of Breast Cancer Treated with Doxorubicin 116

6. Ovarian Cancer 117
6.1 Serum Markers 119
6.2 Biomarkers 120
6.2.1 Strategies for Discovering New Cancer Biomarkers 121
6.3 Serum Protein Biomarkers for Ovarian Cancer 121
6.3.1 Clinical Proteomics 122
6.4 Ovarian Cancer Triage Testing 123
6.4.1 Vermillion's Ovarian Cancer Triage Diagnostic Program 124

7. Prostate Cancer 126
7.1 Overview 126
7.1.1 Prevalence 126
7.1.2 Prostate Cancer Progression and Recurrence Test 126
7.1.3 Current Market Size 126
7.2 Genes Involved in Prostate Cancer 127
7.3 Androgen Independence 128
7.4 Gene Markers in Prostate Cancer 129
7.5 Microarray Gene Identification of Prostate Biomarkers 129
7.6 GEArray DNA Microarrays 131
7.7 Vermillion's Cancer Diagnostic Program 132
7.8 Hepsin 132
7.9 Matritech's Prostate Cancer Program (NMP48) 132
7.10 Gen-Probe's PCA3 Assay 133
7.11 Early Prostate Cancer Antigen-2 (EPCA-2) 133
7.12 Mass Spectrometry 134
7.13 Summary 136

8. Bladder Cancer 137
8.1 Overview 137
8.1.1 Prevalence 137
8.1.2 Progression and Recurrence 137
8.1.3 Bladder Cancer Risk Factors 137
8.1.4 Bladder Cancer Symptoms 137
8.2 Bladder Cancer Tests 137
8.3 UroVysion Bladder Cancer Kit 138
8.4 Ikoniscope® Robotic Digital Microscopy Platform 139
8.4.1 The CellOptics Platform 139
8.4.2 Cell Staining and Genetic Characterization 139
8.4.3 Ikoniscope/IkoniLAN Automated Microscopy 139
8.5 Nuclear Matrix Protein Markers 140
8.6 ImmunoCyt™/uCyt+™ 142
8.7 Cangen Microsatellite DNA 144
8.8 Bladder Cancer Market 144
8.8.1 Urologist Market 144
8.8.2 Clinical Lab Market 144
8.8.3 Primary Care Market 144
8.8.4 Private and Public Sector Markets 145
8.8.5 POC Market 145
8.8.6 Market Distribution 145
8.8.7 Reimbursement 145

9. Colorectal Cancer 146
9.1 Overview 146
9.1.1 Prevalence 146
9.1.2 Progression and Recurrence 146
9.2 Screening for CRC 148
9.2.1 Stool-based DNA (sDNA) Screening 149
9.3 Almac Diagnostics DSA 150
9.4 Colon Cancer Program (NMP35) 151
9.5 Myriad Genetics Colaris AP Risk Assessment 151
9.6 Summary 152

10. Genetic Diagnostics Set to Revolutionize Cancer Diagnostic Testing 153
10.1 Overview 153
10.1.1 Clinicians Need for More Information with Regard to Therapeutic Treatment Drives Demand for Pharmacogenomic Testing 153
10.1.2 Predictive Medicine Shows Potential for Genetic Diagnostics 153
10.1.3 Different Rates of Growth 154
10.1.4 Effective Competitive Strategies 154
10.1.5 Improvements in Marketing Effectiveness 154
10.1.6 Emerging Technologies Imply Start of a New Era and Offer Tremendous Growth Opportunities 154
10.1.7 Increased Market Share 154
10.1.8 Technologies Used in Genetic Testing 154
10.2 AMAS Test 155
10.3 Corixa Antibodies as Tumor Markers 155
10.4 Cytovision 156
10.5 Ariol System 156
10.6 Mammaglobin Protein Expression 156
10.7 L523S or KOC RNA Binding Protein 156
10.8 CA1-18 from EDP Biotech 157

11. Leukemia Biomarkers 158
11.1 Overview 158
11.1.1 Prevalence 158
11.1.1.1 Progression and Recurrence 158

12. Lung Cancer 159

13. Enabling Technologies for Oncology Biomarker Discovery 160
13.1 Automated Cellular Imaging System (ACIS®) 160
13.1.1 ACIS for HER2 Protein Expression Testing 161
13.1.2 ACIS for ER Protein Expression Testing 161
13.1.3 ACIS for PR Protein Expression Testing 161
13.1.4 ACIS for Cell Proliferation Expression 162
13.1.5 ACIS for Protein Expression 162
13.1.6 ACIS for Protein Micrometastases in Bone Marrow 162
13.1.7 ACIS for Protein Micrometastases in Tissue 162
13.1.8 ACIS for Tissue Microarray 162
13.1.9 ACIS for DNA Ploidy 162
13.1.10 ACIS for HPV 162
13.2 DNA Methylation 163
13.2.1 Differential Methylation Hybridization (DMH) 163
13.2.2 MIRA-Assisted Microarrays for DNA Methylation Analysis and Cancer Diagnosis 163
13.3 Proteomics 164
13.3.1 Proteomics Technologies for Cancer Marker Discovery 164
13.3.2 Validation of Candidate Biomarkers 165
13.3.3 Requirements Bringing a New Marker into the Market 165
13.3.4 Value Chain in the Development of New Cancer Biomarkers 166
13.4 Secreted Proteins as Cancer Biomarkers 166
13.4.1 Markers of Known Tissue Origin 166
13.4.2 Secreted Proteins as Low Abundance Markers 166
13.4.3 Secreted Proteins in Tissue and Blood 166
13.5 Noncodings RNA as Potential Tumor Markers 166
13.5.1 miRNA Meets Microarray 167
13.5.2 Mimetics and Inhibitors 167
13.5.3 Clinical Patterns in Cancer 167
13.6 Architect TIMP-1 (Tissue Inhibitor of Metalloproteinases-1) Immunoassay for Colorectal Cancer Detection 167
13.7 Companies Developing Automated Microscope-based Analysis Systems 167
13.8 Companies Developing Research Products for Tumor Cell Isolation 168
13.9 Companies Supplying Fluorescently Labeled Antibodies to Characterize Tumor Cells 168
13.10 PerkinElmer High Throughput Platforms: AlphaScreen®, AequoScreen®, DELFIA® and LANCE® Technologies 168

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

15. Companion Diagnostics and Personalized Medicine: Biology, Approaches, Pipeline and Regulatory Trends 176
15.1 Scope of this Chapter 176
15.2 Introduction to Companion Diagnostics and Personalized Medicine 176
15.3 The Compelling Case for Personalized Medicine 178
15.4 Drug Metabolism and Implications for Companion Diagnostics and Personalized Medicine 179
15.5 Examples of Personalized Medicine 183
15.6 Personalized Medicine and Companion Diagnostics Testing Product Pipeline 185
15.7 The Personalized Medicine Coalition 187
15.8 Regulatory Trends and Guidelines in the Personalized Medicine Space 189
15.8.1 The Changing Regulatory Landscape for Personalized Medicine 191
15.9 Patenting Personalized Medicine 192
15.10 The Leading Edge of Personalized Medicine: Specific Examples of Clinical Situations Where Personalized Medicine and Companion Diagnostics is Appropriate and Being Deployed 194
15.10.1 EGFR Assay 195
15.10.2 Individualized Warfarin Therapy 195
15.10.3 UGT1A1 Molecular Assay for Camptosar 196
15.10.4 Response to Gleevec in Gastrointestinal Stromal Tumors 196
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 197
15.11 Companion Diagnostics and Personalized Medicine: Qualitative and Quantitative Market Analysis 197
15.11.1 Market Analysis of Molecular Diagnostics and Companion Diagnostics and Personalized Medicine 197
15.11.2 Diagnostics vs. Pharmaceuticals 198
15.11.3 Molecular Diagnostic Market 199
15.11.4 Molecular Diagnostics Technology Platforms and their Impact on Personalized Medicine 201
15.12 Snapshot of Companion Diagnostics Industry Structure 203
15.13 The Case for Theranostics (Therapeutic/Companion Diagnostic) 204
15.14 Personalized Medicine Market Analysis-Market Survey Data Characterizing the Qualitative and Quantitative Industry Parameters 205
15.15 How the Market Segregates Today 206
15.16 Timeline for Impact of Various Segments in Personalized Medicine 207
15.17 Challenges for Personalized Therapeutics and Companion Diagnostics Development 209
15.18 Macro Trends in Personalized Medicine 209
15.19 Personalized Medicine and Companion Diagnostics: Industry SWOT Analysis 213

16. Cancer Biomarker Testing Sector and Company Analysis 215
16.1 Abbott Molecular, Inc. (Formerly Vysis, Inc.) 215
16.2 Agendia 217
16.3 AMDL, Inc. 217
16.4 Aureon Laboratories, Inc. 217
16.5 BioCurex 217
16.6 Biomarker Technologies 217
16.7 Biomedical Diagnostics LLC 217
16.8 Biomerica 218
16.9 Biomira, Inc. 218
16.10 Biomoda 218
16.11 Byk Gulden 218
16.12 Clarient 219
16.13 Correlogic Systems, Inc. 220
16.14 Cytogen Corporation 220
16.15 Dako (Formerly Dako Cytomation) 221
16.16 diaDexus 222
16.17 Diagnocure, Inc. (ImmunoCyt™/uCyt+™) 222
16.18 DxS Ltd. 223
16.19 Epigenomics 224
16.20 Exagen Diagnostics, Inc. 225
16.21 Genesis Genomics 226
16.22 Health Discovery Corporation 226
16.23 Immunicon 226
16.24 Ipsogen 227
16.25 InterGenetics 228
16.26 Miraculins, Inc. 229
16.27 Molecular Devices Inc. (Formerly Arcturus Bioscience, Inc.) 229
16.28 Myriad Genetics, Inc. 229
16.29 Orion Genomics 230
16.30 Power3 Medical Products 230
16.31 Qiagen N.V. 231
16.32 SuperArray Bioscience Corporation 231
16.33 Upstream Biosciences, Inc. 231
16.34 Ventana Medical Systems, Inc. 232
16.35 Veridex 232
16.36 Vermillion 233

17. Business Trends in the Industry 237
17.1 Industry Consolidation 237
17.2 Breadth of Product Offering and Pricing 238
17.3 Government Regulation of Medical Devices 238
17.3.1 FDA Guidance on Drug Test Co-development 240
17.4 Strategic Business and Marketing Considerations 240
17.5 Commercial Opportunities in Cancer Markers 240
17.5.1 Licensing and Intellectual Property (IP) Constraints and how they will Impact New Product Development 241
17.6 Moderators of Growth 241
17.6.1 Roadblocks to Integrating Cancer Biomarkers into Clinical Practice 242
17.7 Biotechnology Industry Trends 242
17.8 Pharmaceutical Industry Trends 243
17.9 Acquisition, License Agreement, Partnerships 244
17.10 Legal Developments 247
17.11 Sales and Marketing Strategies for Tumor Marker Tests 248
17.11.1 North American Market 249
17.11.2 International Markets 250
17.11.2.1 Europe 250
17.11.2.2 Central and South America 251
17.11.2.3 Asia/Pacific 251
17.12 Product Commercialization 251
17.13 Reimbursement 252
17.14 Self Referral Rules 253
17.15 Health Insurance Portability and Accountability Act 254
17.16 Clinical Laboratory Improvement Amendments (CLIA) 254
17.17 In-Vitro Diagnostic Directive (IVDD) and Medical Device Regulations 255
17.18 FDA's Quality System Regulation (QSR) 256
17.19 FDA's OIVD on IVDMIAs 256
17.20 FDA's Qualification of Cancer Biomarkers 257
17.20.1 Regulatory Perspectives of Biomarker Validation 257
17.21 Genetic Tests and Medical Records 257
17.21.1 Laws against Genetic Discrimination 258
17.22 Medicare Reimbursement 259
17.22.1 Medicare Part B Spending Trends 259
17.23 Global Drivers of Clinical Laboratory Testing 261
17.24 Global Outlook for Cancer Biomarkers 261
17.24.1 Which Companies are Utilizing Cutting-Edge Technologies to Develop, Validate and Implement Cancer Biomarkers for Clinical Use? 262
17.24.2 What Impediments Still Exist to Incorporating Promising Research into Clinical Practice? 262
17.24.3 Which Biomarkers Show the Most Promise for Approval? 263
17.24.4 How can Regulatory Oversight Drive Approval and Adoption of New Technologies? 263
17.24.5 Which Alliances Show the Greatest Synergy in Bringing Valid Biomarkers to Market? 263
17.24.6 Which Shared Technologies are Driving the Most Encouraging Development? 263
17.24.7 How Strategic Alliances and Interdisciplinary Involvement Drive Development and Implementation of Emerging Biomarker Technologies 264
17.25 Oncology Biomarker Qualification Initiative 264
17.26 FDA Critical Path 265
17.27 FDA Criteria for a Valid Biomarker 265

18. Companies Entering the Cancer Diagnostics Market with Novel Technology Platforms 266
18.1 Abbott Diagnostics 266
18.2 Affymetrix, Inc. 268
18.3 Agendia BV 270
18.4 Agensys, Inc. 271
18.5 Almac Group 271
18.6 AMDL, Inc. 271
18.7 Aureon Laboratories, Inc. 273
18.8 Bayer Diagnostics Corporation 274
18.9 Beckman Coulter, Inc. 274
18.10 Biocode S.A. 275
18.11 BioCurex, Inc. 276
18.12 Biomarker Technologies LLC 276
18.13 Biomedical Diagnostics LLC 276
18.14 Biomerica 276
18.15 bioMérieux 277
18.16 Biomira, Inc. 277
18.17 Biomoda, Inc. 278
18.18 Bruker Daltonics, Inc. 279
18.19 Byk Gulden 279
18.20 Cangen Biotechnologies, Inc. 279
18.21 Caprion Proteomics 281
18.22 Celera Diagnostics 281
18.23 Cepheid 282
18.24 Clarient, Inc. 283
18.25 Claros Diagnostics, Inc. 284
18.26 Clinical Data, Inc.: PGxHealth and Cogenics 284
18.27 Correlogic Systems, Inc. 285
18.28 CytoCore (Formerly Molecular Diagnostics, Inc.) 286
18.29 Cytogen Corporation 286
18.30 Dako (Formerly Dako Cytomation) 289
18.31 diaDexus LLC 290
18.32 DiagnoCure, Inc. 291
18.33 Diagnostic Products Corporation 292
18.34 Diagnostic Systems Laboratories, Inc. 292
18.35 Digene Corporation 292
18.36 DRG International, Inc. 293
18.37 DxS Ltd. 293
18.38 EDP Biotech Corporation 294
18.39 Eisai Co., Ltd. 295
18.40 Epigenomics 295
18.41 Exact Sciences Corporation 296
18.42 Exagen Diagnostics, Inc. 296
18.43 Gene Logic, Inc. 297
18.44 Genesis Genomics, Inc. 298
18.45 Genomic Health, Inc. 298
18.46 Gen-Probe, Inc. 298
18.47 Health Discovery Corporation 299
18.48 Hologic, Inc. (Formerly Cytyc Corporation) 300
18.49 Ikonisys, Inc. 300
18.50 Immunicon Corporation 301
18.51 Immunomedics, Inc. 305
18.52 Incyte Pharmaceuticals, Inc. 306
18.53 InterGenetics® 306
18.54 Ipsogen 306
18.55 LabCorp® 307
18.56 Matritech, Inc. 308
18.57 Miraculins, Inc. 310
18.58 Mitsubishi Kagaku Medical 311
18.59 Molecular Devices (Formerly Arcturus Biosciences, Inc.) 311
18.60 Myriad Genetics, Inc. 311
18.61 NimbleGen Systems, Inc. 316
18.62 Northwest Biotherapeutics, Inc. 316
18.63 Oncotech, Inc. 317
18.64 Orion Genomics 318
18.65 Oxford Genome Sciences 318
18.66 Panacea Pharmaceuticals, Inc. 319
18.67 Phenomenone Discoveries 319
18.68 Polymedco, Inc. 319
18.69 Power3 Medical Products 320
18.70 Proteome Systems Ltd. 320
18.71 Qiagen N.V. 321
18.72 Sanko Junyaku Co., Ltd. 322
18.73 SensiGen LLC 322
18.74 SuperArray Bioscience Corporation 322
18.75 Third Wave Technologies, Inc. 322
18.76 Tosoh Medics, Inc. 323
18.77 TriPath Imaging, Inc. 323
18.78 Upstream Biosciences, Inc. 325
18.79 Ventana Medical Systems, Inc. 325
18.80 Veridex LLC 326
18.81 Vermillion, Inc. (Formerly Ciphergen) 327

Appendix 1: Cancer Biomarker Centers of Research 330

Appendix 2: Myriad Patents on Genes BRAC1 and BRAC2 331

Appendix 3: Common Laboratory Tests for Cancer 332

Appendix 4: Questions/Issues in the Cancer Biomarkers Space 339

Appendix 5: Cancer Markers Currently in Common Clinical Use 341

Appendix 6: International Federation of Gynecology and Obstetrics (FIGO) Staging System for Primary Carcinoma of the Ovary 342

Appendix 7: FDA Guidance for Industry: Pharmacogenomic Data Submission 343
A7.1 Introduction 343
A7.2 Background 343
A7.3 Submission Policy 344
A7.3.1 General Principles 344
A7.3.2 Specific Uses of Pharmacogenomic Data in Drug Development and Labeling 346
A7.3.3 Benefits of Voluntary Submissions to Sponsors and FDA 347
A7.4 Submission of Pharmacogenomic Data 348
A7.4.1 Submission of Pharmacogenomic Data During the IND Phase 348
A7.4.2 Submission of Pharmacogenomic Data to a New NDA, BLA, or Supplement 349
A7.4.3 Submission to a Previously Approved NDA or BLA 350
A7.4.4 Compliance with 21 CFR Part 58 350
A7.4.5 Submission of Voluntary Genomic Data from Application-Independent Research 351
A7.5 Format and Content of a VGDS 351
A7.6 Process for Submitting Pharmacogenomic Data 352
A7.7 Agency Review of VGDSs 352

Glossary 354

INDEX OF FIGURES

Figure 3.1: Potential Market for Cancer Biomarkers, 2006 48
Figure 3.2: Segmentation of the Cancer biomarkers Marketplace Based Upon Commercial Offerings-Products and Services 51
Figure 3.3: Geographical Distribution of Cancer Tumor Diagnostic Testing 55
Figure 3.4: Cancer Biomarkers Research Market, 2006-2011 60
Figure 3.5: Breast Cancer Biomarker Market Potential, 2005 66
Figure 3.6: Challenges in the Study or Utilization of Proteomic Cancer Biomarkers 67
Figure 3.7: Challenges in the Study or Utilization of Companion Diagnostic Cancer Biomarkers 67
Figure 3.8: Challenges in the Study or Utilization of Serum Cancer Markers 68
Figure 3.9: Top Unmet Needs in Commercial Products in the Cancer Biomarkers Space 69
Figure 5.1: Hybridization Process 86
Figure 5.2: FISH Test Procedure 87
Figure 5.3: Gene Expression Profiling 97
Figure 15.1: Phase I and II Processes of Drug Metabolism 179
Figure 15.2: Human Phase I Enzymes 180
Figure 15.3: Human Phase II Enzymes 180
Figure 15.4: Hepatic Distribution of Human CYP450 181
Figure 15.5: Relative Contribution of CYP450 Enzymes to Drug Metabolism 181
Figure 15.6: Genetic Components Determine Drug Metabolism 182
Figure 15.7: From Genetic Content to Personalized Medicine 198
Figure 15.8: Remuneration for Diagnostics 198
Figure 15.9: Breakout of the Molecular Diagnostics Marketplace 199
Figure 15.10: Molecular Diagnostics Market Segmentation 200
Figure 15.11: Molecular Diagnostics Market Segmentation by Technology 201
Figure 15.12: Market Survey Respondent Demographics 205
Figure 15.13: Breakout of the Respondent Pool by Affiliation 206
Figure 15.14: Segmentation of the Personalized Medicine Market 206
Figure 15.15: Personalized Medicine Market Drivers 210
Figure 15.16: Challenges in the Personalized Medicine Space 211
Figure 16.1: Epigenomics Product Development Pipeline 225
Figure 17.1: Medicare Part B Spending on Clinical Laboratory Services, 1991-2005 259

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, 1999-2007 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: Market Opportunities for Cancer Biomarker Technology Platforms 44
Table 3.1: Characteristics of Different Cancer Biomarker Types and Associated Market Opportunities 50
Table 3.2: Segmentation of the Cancer Biomarker Market by Type/Lineage of Cancer Biomarkers and Market Size 50
Table 3.3: In Vitro Cancer Marker Market Segments Worldwide, 2001 and 2007 52
Table 3.4: Worldwide Market Size in Dollar Volume for Tumor Marker Assays Product Market, 2001-2010 52
Table 3.5: U.S. Market Size in Dollar Volume for Tumor Marker Assays Product Market, 2001-2010 53
Table 3.6: Worldwide In Vitro Cancer Tumor Marker Diagnostics Market Size, 2001-2010 53
Table 3.7: U.S. In Vitro Cancer Tumor Marker Diagnostics Market Size, 2001-2010 53
Table 3.8: Japanese In Vitro Cancer Tumor Marker Diagnostics Market Size, 2001-2010 54
Table 3.9: European In Vitro Cancer Tumor Marker Diagnostics Market Size, 2001-2010 54
Table 3.10: Global Distribution of IVD Cancer Tumor Marker Diagnostic Testing, 2005 54
Table 3.11: Estimated Market Share of Major Competitors in U.S. Cancer Tumor Marker Diagnostics Market 55
Table 3.12: Major Presence in Cancer Tumor Marker Diagnostics Markets 55
Table 3.13: Worldwide CEA Sales, 2001-2010 56
Table 3.14: U.S. CEA Sales, 2001-2010 57
Table 3.15: Cancer Genomic Biomarker Markets, 2002-2012 57
Table 3.16: Cancer Biomarkers Research Market Forecast, 2006-2011 60
Table 3.17: Cancer Biomarker Market Estimates by Tissue of Origin 64
Table 3.18: Companies Developing New Proteomic Cancer Biomarker Technology Platforms 72
Table 4.1: Cancer Biomarkers Used to Maximize Likelihood of Response 74
Table 4.2: Biomarkers for Monitoring Therapeutic Effectiveness and Resistance 74
Table 4.3: Biomarkers for Dose Response of Therapy 74
Table 4.4: Decision on Optimal Duration of Therapy 74
Table 5.1: U.S. Breast Cancer Rate Decline, 2002-2006 77
Table 5.2: BRCA Development Model 79
Table 5.3: BRCA Test Development and Commercialization 80
Table 5.4: BRAC Analysis 80
Table 5.5: Revenue for BRACAnalysis® Risk Assessment Test, 2002-2006 80
Table 5.6: GEArray DNA Microarrays and RT2 Profiler PCR Arrays 97
Table 5.7: Product Development Opportunities in Breast Cancer 104
Table 5.8: Concentration of Some Abundant Proteins, New Cancer Biomarkers Identified by SELDI-TOF, and Classical Cancer Biomarkers in Serum 111
Table 5.9: Questions Related to Diagnostic SELDI-TOF Technology 113
Table 6.1: Worldwide CA-125 Sales, 2001-2010 117
Table 6.2: U.S. CA-125 Sales, 2001-2010 118
Table 6.3: Some Clinically Established Cancer Serum Markers Currently in Use for Cancer 119
Table 6.4: Pathophysiology of Ovarian Cancer and Characterization of Ovarian Epithelial Tumors 125
Table 7.1: Worldwide PSA Sales, 2000-2010 127
Table 7.2: U.S. PSA Sales, 2000-2010 127
Table 7.3: Molecular Gene Markers for Prostate Cancer 129
Table 8.1: Worldwide Bladder Cancer Marker Sales, 2001-2010 141
Table 8.2: U.S. Bladder Cancer Marker Sales, 2001-2010 141
Table 8.3: Worldwide NMP22 Sales, 2001-2010 142
Table 8.4: Summary of Matritech's Product Development Programs 143
Table 8.5: Opportunities for Bladder Cancer Biomarkers 144
Table 9.1: TNM Staging for Colorectal Cancer 147
Table 10.1: Genetic Diagnostics Market, 2004-2012 153
Table 13.1: Genomic and Proteomic Technologies 165
Table 14.1: Potential Benefits of Biomarkers as Companion Diagnostics 171
Table 14.2: Utility of Biomarker as Companion Diagnostics to Drug Development 171
Table 14.3: Device Submission Elements for the FDA 174
Table 14.4: Summary of Biomarker Use in the Commercialization of Novel Oncology Pharmacotherapeutics 175
Table 14.5: Pharmacoeconomic Challenges to the Implementation of Biomarkers as Companion Diagnostic Tests 175
Table 15.1: Percentage of Non-Responders in Various Drug Classes 178
Table 15.2: High Profile Drug Withdrawals from the Marketplace 178
Table 15.3: Drug Metabolism Drives Drug Efficacy/Toxicity 183
Table 15.4: Population Frequency of the Various Cytochromes 183
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 201
Table 15.9: Various Molecular Diagnostics Technologies: Impact on Different Therapeutic Areas in Personalized Medicine 202
Table 15.10: Various Molecular Diagnostics Technologies: Technical Challenges in the Deployment for Personalized Medicine 202
Table 15.11: Classification of Diagnostics by Risk 204
Table 15.12: Areas in Personalized Medicine-Timeline of Impact 207
Table 15.13: Impact of Personalized Medicine on Various Therapeutic Areas 208
Table 15.14: Hurdles in Personalized Medicine and Companion Diagnostics Development in Various Therapeutic Areas 209
Table 15.15: Market Opportunities in Personalized Medicine 212
Table 15.16: Challenges for Market Adoption of the Various Personalized Medicine Tests 213
Table 15.17: Personalized Medicine Industry SWOT 214
Table 16.2: Clarient Revenue, 2002-2006 219
Table 16.3: Clarient Percentage of Revenue, 2004-2006 219
Table 16.4: Opportunities for Biomarkers in Cancer Diagnosis and Treatment 220
Table 16.5: Myriad Biomarker Revenue, 2002-2006 230
Table 17.1: List and Discounted Prices for Abbott Tumor Marker Tests 238
Table 17.2: Hospital Laboratory Share of Part B Medicare Spending, 1996-2005 259
Table 17.3: Medicare Spending on Clinical Lab Services, 1991-2005 260
Table 17.4: Medicare Part B Spending Per Medicare Enrollee, 1998-2005 260
Table 18.1: Tumor Diagnosis Immunoassay 293
Table 18.2: Tumor Diagnosis Radioimmunoassay 293
Table 18.3: Summary of Matritech's Product Development Programs 310
Table A1: Team Descriptions 330
Table A5: Cancer Markers in Use 341