Biomarker Technology Platforms for Cancer Diagnoses and Therapies

SUMMARY

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

• 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. Introduction to Cancer Biology and the Diagnostic Industry

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

3. Market Analysis of the Cancer Biomarkers Space

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

4. Major Clinical Applications of Cancer Biomarkers

• 4.1 Launched Products and Pipeline
• 4.2 CYP2C9 Pharmacogenetics and Role in Personalized Medicine
• 4.3 Personalized Breast Cancer Therapy
• 4.4 Personalized NSCLC Therapy
• 4.5 AmpliChip®-based Personalized Medicine

5. Breast Cancer

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

6. Ovarian Cancer

• 6.1 Serum Markers
• 6.2 Biomarkers
  • 6.2.1 Strategies for Discovering New Cancer Biomarkers
• 6.3 Serum Protein Biomarkers for Ovarian Cancer
  • 6.3.1 Clinical Proteomics
• 6.4 Ovarian Cancer Triage Testing
  • 6.4.1 Vermillion's Ovarian Cancer Triage Diagnostic Program

7. Prostate Cancer

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

8. Bladder Cancer

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

9. Colorectal Cancer

• 9.1 Overview
  • 9.1.1 Prevalence
  • 9.1.2 Progression and Recurrence
• 9.2 Screening for CRC
  • 9.2.1 Stool-based DNA (sDNA) Screening
• 9.3 Almac Diagnostics DSA
• 9.4 Colon Cancer Program (NMP35)
• 9.5 Myriad Genetics Colaris AP Risk Assessment
• 9.6 Summary

10. Genetic Diagnostics Set to Revolutionize Cancer Diagnostic Testing

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

11. Leukemia Biomarkers

• 11.1 Overview
  • 11.1.1 Prevalence
    • 11.1.1.1 Progression and Recurrence

12. Lung Cancer

13. Enabling Technologies for Oncology Biomarker Discovery

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

14. Biomarker Tests Co-developed with Cancer Therapeutics as Companion Diagnostics

• 14.1 Sector Overview
• 14.2 Companion Diagnostics
• 14.3 EGFR for Colorectal Cancer and Camptostar (Irinotecan)
• 14.4 EGFR Express and Erbitux (Cetuximab)
• 14.5 HER2 and Heceptin
• 14.6 Myriad's TheraGuide 5-FU
• 14.7 TheraScreen: EGFR29
• 14.8 Drivers and Barriers to Companion Diagnostics
• 14.9 Partnerships with Pharma Companies to Identify Therapeutic Targets
• 14.10 Future Developments for Companion Diagnostics

15. Companion Diagnostics and Personalized Medicine: Biology, Approaches, Pipeline and Regulatory Trends

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

16. Cancer Biomarker Testing Sector and Company Analysis

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

17. Business Trends in the Industry

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

18. Companies Entering the Cancer Diagnostics Market with Novel Technology Platforms

• 18.1 Abbott Diagnostics
• 18.2 Affymetrix, Inc.
• 18.3 Agendia BV
• 18.4 Agensys, Inc.
• 18.5 Almac Group
• 18.6 AMDL, Inc.
• 18.7 Aureon Laboratories, Inc.
• 18.8 Bayer Diagnostics Corporation
• 18.9 Beckman Coulter, Inc.
• 18.10 Biocode S.A.
• 18.11 BioCurex, Inc.
• 18.12 Biomarker Technologies LLC
• 18.13 Biomedical Diagnostics LLC
• 18.14 Biomerica
• 18.15 bioMérieux
• 18.16 Biomira, Inc.
• 18.17 Biomoda, Inc.
• 18.18 Bruker Daltonics, Inc.
• 18.19 Byk Gulden
• 18.20 Cangen Biotechnologies, Inc.
• 18.21 Caprion Proteomics
• 18.22 Celera Diagnostics
• 18.23 Cepheid
• 18.24 Clarient, Inc.
• 18.25 Claros Diagnostics, Inc.
• 18.26 Clinical Data, Inc.: PGxHealth and Cogenics
• 18.27 Correlogic Systems, Inc.
• 18.28 CytoCore (Formerly Molecular Diagnostics, Inc.)
• 18.29 Cytogen Corporation
• 18.30 Dako (Formerly Dako Cytomation)
• 18.31 diaDexus LLC
• 18.32 DiagnoCure, Inc.
• 18.33 Diagnostic Products Corporation
• 18.34 Diagnostic Systems Laboratories, Inc.
• 18.35 Digene Corporation
• 18.36 DRG International, Inc.
• 18.37 DxS Ltd.
• 18.38 EDP Biotech Corporation
• 18.39 Eisai Co., Ltd.
• 18.40 Epigenomics
• 18.41 Exact Sciences Corporation
• 18.42 Exagen Diagnostics, Inc.
• 18.43 Gene Logic, Inc.
• 18.44 Genesis Genomics, Inc.
• 18.45 Genomic Health, Inc.
• 18.46 Gen-Probe, Inc.
• 18.47 Health Discovery Corporation
• 18.48 Hologic, Inc. (Formerly Cytyc Corporation)
• 18.49 Ikonisys, Inc.
• 18.50 Immunicon Corporation
• 18.51 Immunomedics, Inc.
• 18.52 Incyte Pharmaceuticals, Inc.
• 18.53 InterGenetics®
• 18.54 Ipsogen
• 18.55 LabCorp®
• 18.56 Matritech, Inc.
• 18.57 Miraculins, Inc.
• 18.58 Mitsubishi Kagaku Medical
• 18.59 Molecular Devices (Formerly Arcturus Biosciences, Inc.)
• 18.60 Myriad Genetics, Inc.
• 18.61 NimbleGen Systems, Inc.
• 18.62 Northwest Biotherapeutics, Inc.
• 18.63 Oncotech, Inc.
• 18.64 Orion Genomics
• 18.65 Oxford Genome Sciences
• 18.66 Panacea Pharmaceuticals, Inc.
• 18.67 Phenomenone Discoveries
• 18.68 Polymedco, Inc.
• 18.69 Power3 Medical Products
• 18.70 Proteome Systems Ltd.
• 18.71 Qiagen N.V.
• 18.72 Sanko Junyaku Co., Ltd.
• 18.73 SensiGen LLC
• 18.74 SuperArray Bioscience Corporation
• 18.75 Third Wave Technologies, Inc.
• 18.76 Tosoh Medics, Inc.
• 18.77 TriPath Imaging, Inc.
• 18.78 Upstream Biosciences, Inc.
• 18.79 Ventana Medical Systems, Inc.
• 18.80 Veridex LLC
• 18.81 Vermillion, Inc. (Formerly Ciphergen)

Appendix 1: Cancer Biomarker Centers of Research

Appendix 2: Myriad Patents on Genes BRAC1 and BRAC2

Appendix 3: Common Laboratory Tests for Cancer

Appendix 4: Questions/Issues in the Cancer Biomarkers Space

Appendix 5: Cancer Markers Currently in Common Clinical Use

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

Appendix 7: FDA Guidance for Industry: Pharmacogenomic Data Submission

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

Glossary

INDEX OF FIGURES

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

INDEX OF TABLES

• Table 2.1: Cancer Biomarkers at the Nexus Point
• Table 2.2: Drug Development by Type of Cancer
• Table 2.3: Organ Specific Medicines in Development for Cancer, 2006
• Table 2.4: Estimates for the Leading Sites of New Cancer Cases and Deaths in the U.S. by Sex, 2007
• Table 2.5: Estimated Worldwide Number of New Cancer Cases and Deaths by Type of Cancer
• Table 2.6: Estimated Number of New Cancer Cases and Deaths by Region
• Table 2.7: Cancer Death Rates per 100,000 Population (and Rank) for All Cancer Sites by Country
• Table 2.8: Cancer Associated Genes
• Table 2.9: Carcinogens in the Workplace
• Table 2.10: Cancer Biomarker Markets
• Table 2.11: Private Funding Levels for the Biotechnology Segment, 1995-2006
• Table 2.12: Global Pharmaceutical Industry R&D Spending, 1995-2006
• Table 2.13: U.S. Government NIH Research Budget, 1995-2007
• Table 2.14: Tumor Markers Currently in Common Use
• Table 2.15: Herceptin Worldwide Sales, 1999-2007
• Table 2.16: Classes of Drugs Used to Treat Breast Cancer
• Table 2.17: Solutions to Biomarker Developments
• Table 2.18: Vermillion Collaborations
• Table 2.19: Uses of Molecular Diagnostics in Detection and Management of Cancer
• Table 2.20: U.S. Cancer Diagnostic Testing Market Size, 2005-2012
• Table 2.21: Market Opportunities for Cancer Biomarker Technology Platforms
• Table 3.1: Characteristics of Different Cancer Biomarker Types and Associated Market Opportunities
• Table 3.2: Segmentation of the Cancer Biomarker Market by Type/Lineage of Cancer Biomarkers and Market Size
• Table 3.3: In Vitro Cancer Marker Market Segments Worldwide, 2001 and 2007
• Table 3.4: Worldwide Market Size in Dollar Volume for Tumor Marker Assays Product Market, 2001-2010
• Table 3.5: U.S. Market Size in Dollar Volume for Tumor Marker Assays Product Market, 2001-2010
• Table 3.6: Worldwide In Vitro Cancer Tumor Marker Diagnostics Market Size, 2001-2010
• Table 3.7: U.S. In Vitro Cancer Tumor Marker Diagnostics Market Size, 2001-2010
• Table 3.8: Japanese In Vitro Cancer Tumor Marker Diagnostics Market Size, 2001-2010
• Table 3.9: European In Vitro Cancer Tumor Marker Diagnostics Market Size, 2001-2010
• Table 3.10: Global Distribution of IVD Cancer Tumor Marker Diagnostic Testing, 2005
• Table 3.11: Estimated Market Share of Major Competitors in U.S. Cancer Tumor Marker Diagnostics Market
• Table 3.12: Major Presence in Cancer Tumor Marker Diagnostics Markets
• Table 3.13: Worldwide CEA Sales, 2001-2010
• Table 3.14: U.S. CEA Sales, 2001-2010
• Table 3.15: Cancer Genomic Biomarker Markets, 2002-2012
• Table 3.16: Cancer Biomarkers Research Market Forecast, 2006-2011
• Table 3.17: Cancer Biomarker Market Estimates by Tissue of Origin
• Table 3.18: Companies Developing New Proteomic Cancer Biomarker Technology Platforms
• Table 4.1: Cancer Biomarkers Used to Maximize Likelihood of Response
• Table 4.2: Biomarkers for Monitoring Therapeutic Effectiveness and Resistance
• Table 4.3: Biomarkers for Dose Response of Therapy
• Table 4.4: Decision on Optimal Duration of Therapy
• Table 5.1: U.S. Breast Cancer Rate Decline, 2002-2006
• Table 5.2: BRCA Development Model
• Table 5.3: BRCA Test Development and Commercialization
• Table 5.4: BRAC Analysis
• Table 5.5: Revenue for BRACAnalysis® Risk Assessment Test, 2002-2006
• Table 5.6: GEArray DNA Microarrays and RT2 Profiler PCR Arrays
• Table 5.7: Product Development Opportunities in Breast Cancer
• Table 5.8: Concentration of Some Abundant Proteins, New Cancer Biomarkers Identified by SELDI-TOF, and Classical Cancer Biomarkers in Serum
• Table 5.9: Questions Related to Diagnostic SELDI-TOF Technology
• Table 6.1: Worldwide CA-125 Sales, 2001-2010
• Table 6.2: U.S. CA-125 Sales, 2001-2010
• Table 6.3: Some Clinically Established Cancer Serum Markers Currently in Use for Cancer
• Table 6.4: Pathophysiology of Ovarian Cancer and Characterization of Ovarian Epithelial Tumors
• Table 7.1: Worldwide PSA Sales, 2000-2010
• Table 7.2: U.S. PSA Sales, 2000-2010
• Table 7.3: Molecular Gene Markers for Prostate Cancer
• Table 8.1: Worldwide Bladder Cancer Marker Sales, 2001-2010
• Table 8.2: U.S. Bladder Cancer Marker Sales, 2001-2010
• Table 8.3: Worldwide NMP22 Sales, 2001-2010
• Table 8.4: Summary of Matritech's Product Development Programs
• Table 8.5: Opportunities for Bladder Cancer Biomarkers
• Table 9.1: TNM Staging for Colorectal Cancer
• Table 10.1: Genetic Diagnostics Market, 2004-2012
• Table 13.1: Genomic and Proteomic Technologies
• Table 14.1: Potential Benefits of Biomarkers as Companion Diagnostics
• Table 14.2: Utility of Biomarker as Companion Diagnostics to Drug Development
• Table 14.3: Device Submission Elements for the FDA
• Table 14.4: Summary of Biomarker Use in the Commercialization of Novel Oncology Pharmacotherapeutics
• Table 14.5: Pharmacoeconomic Challenges to the Implementation of Biomarkers as Companion Diagnostic Tests
• Table 15.1: Percentage of Non-Responders in Various Drug Classes
• Table 15.2: High Profile Drug Withdrawals from the Marketplace
• Table 15.3: Drug Metabolism Drives Drug Efficacy/Toxicity
• Table 15.4: Population Frequency of the Various Cytochromes
• Table 15.5: Selected List of Personalized Medicine Tests
• Table 15.6: Personalized Medicine and Companion Diagnostics Product Pipeline
• Table 15.7: Marketed Personalized Therapies, 2006
• Table 15.8: Various Molecular Diagnostics Technologies: Timeline for Impact
• Table 15.9: Various Molecular Diagnostics Technologies: Impact on Different Therapeutic Areas in Personalized Medicine
• Table 15.10: Various Molecular Diagnostics Technologies: Technical Challenges in the Deployment for Personalized Medicine
• Table 15.11: Classification of Diagnostics by Risk
• Table 15.12: Areas in Personalized Medicine-Timeline of Impact
• Table 15.13: Impact of Personalized Medicine on Various Therapeutic Areas
• Table 15.14: Hurdles in Personalized Medicine and Companion Diagnostics Development in Various Therapeutic Areas
• Table 15.15: Market Opportunities in Personalized Medicine
• Table 15.16: Challenges for Market Adoption of the Various Personalized Medicine Tests
• Table 15.17: Personalized Medicine Industry SWOT
• Table 16.2: Clarient Revenue, 2002-2006
• Table 16.3: Clarient Percentage of Revenue, 2004-2006
• Table 16.4: Opportunities for Biomarkers in Cancer Diagnosis and Treatment
• Table 16.5: Myriad Biomarker Revenue, 2002-2006
• Table 17.1: List and Discounted Prices for Abbott Tumor Marker Tests
• Table 17.2: Hospital Laboratory Share of Part B Medicare Spending, 1996-2005
• Table 17.3: Medicare Spending on Clinical Lab Services, 1991-2005
• Table 17.4: Medicare Part B Spending Per Medicare Enrollee, 1998-2005
• Table 18.1: Tumor Diagnosis Immunoassay
• Table 18.2: Tumor Diagnosis Radioimmunoassay
• Table 18.3: Summary of Matritech's Product Development Programs
• Table A1: Team Descriptions
• Table A5: Cancer Markers in Use