個人化醫療與癌症治療上的搭配診斷

本報告，彙整搭配診斷試驗於個人化醫療上的使用動向，並加入定性以及定量市場分析、法規動向、業界參與企業，由下列摘要形式闡述。

第1章 報告書的概要

第2章 搭配診斷與個人化醫療

• 本章的範圍
• 搭配診斷與個人化醫療的簡介
• 藥劑代謝性與搭配診斷以及個人化醫療
• 搭配診斷與個人化醫療的事例
• 個人化醫療與搭配診斷試驗產品線
• 個人化醫療的結合
• 個人化醫療領域的法規動向與方針
• 搭配診斷在癌症治療上的角色日益吃重
• 搭配診斷上所發展的臨床事例
• 癌症治療效果分析的診斷試驗
• 價值鏈
• CDx/PM對藥劑臨床試驗的影響

第3章 搭配診斷：定量以及定性市場分析

• 分子診斷與搭配診斷市場分析
• 搭配診斷於醫療費用上的成本
• 分子診斷市場
• 分子診斷技術平台與對臨床的影響
• 搭配診斷業界結構
• 治療診斷科技事例
• 搭配診斷市場分析：以具定性以及定量的業界參數為特徵的市場調查資料

第4章 動向與概要

• 搭配診斷：SWOT分析
• 搭配診斷的宏觀動向
• 搭配診斷發展的課題
• 搭配診斷上各種區塊的影響
• 個人化試驗開發上蛋白質體學的利用
• 市場問題：個人化醫療上的診斷價值創造

第5章 做為搭配診斷而與癌症治療所共同開發的生物標記試驗

• 概要
• 市場的搭配診斷
• 表皮增殖因子受體搭配
• 以Myriad的IVDMIA技術為基礎的搭配
• 酪胺酸酶抑制劑的搭配
• 抗癌妥與UGT1A1
• Gllevec搭配　其他

第6章 搭配生物標記試驗領域的商業以及法規動向

• 業界整合
• 產品提供與價格
• 政府的醫療機器規範
• 策略性商業・市場行銷考察
• 搭配標記的商業機會
• 增殖調節因子
• 整合搭配生物標記於臨床上的障礙
• 第三方的標的療法管理
• 生物科技業界動向
• 醫藥品業界動向
• 收購、專利契約、合作
• 法規發展
• 腫瘤檢查的業務・市場行銷策略
• 產品化
• 醫療報銷
• 自我介紹規定　其他

第7章 搭配診斷市場的參與企業

附錄

Abstract

A near-term market opportunity for cancer companion diagnostic tests exists in drug selection for cancer therapy. Co-development of molecular diagnostics and targeted therapeutics has already been proven to be a successful strategy in the development of novel anti-cancer drugs. Adoption of biomarker development in clinical research provides great opportunities to identify patient subpopulations with differential drug responses and to uncover the underlying mechanisms. These data could help to explain if clinical trials of new drugs are adequate, and offer the possibility of creating a clear prescription path based on predictive biomarkers. The purpose of this TriMark Publications report is to describe the specific segment of the diagnostics market that develops new technology platforms for evaluating the metabolism of therapeutic agents, or for evaluating which therapeutic regimes are most effective for a particular type of disease. The term companion diagnostic means that the particular diagnostic test under evaluation is specifically linked to a known therapeutic drug. This linkage could be important in the therapeutic application and clinical outcome of a drug (personalized medicine), or an important component of the drug development process. This report focuses on the former linkage, i.e., the use of companion diagnostic tests in personalized medicine.

Table of Contents

1. Overview

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

2. Companion Diagnostics and Personalized Medicine

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

3. Companion Diagnostics: Qualitative and Quantitative Market Analysis

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

4. Trends and Overview

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

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

• 5.1 Sector Overview
  • 5.1.1 Impact of New Technology Platforms
  • 5.1.2 Impact on Drug Discovery
  • 5.1.3 Biomarkers as Endpoints in Drug Discovery
  • 5.1.4 Targeted Therapy
• 5.2 Companion Diagnostics on the Market
• 5.3 Epidermal Growth Factor Receptor Companions
  • 5.3.1 Bevacizamab (Avastin)
  • 5.3.2 EGFR for Colorectal Cancer and Camptosar (Irinotecan)
    • 5.3.2.1 Companion Diagnostic Test Developed for UGT1A1 for Irinotecan
    • 5.3.2.2 Companion Diagnostic Test Developed for Bristol-Myers' s SPRYCEL
  • 5.3.3 EGFR Express and Erbitux (Cetuximab)
  • 5.3.4 HER2 and Heceptin (Trastuzumab)
    • 5.3.4.1 Bayer' s Advia Centaur HER2/neu Assay
    • 5.3.4.2 Companies Marketing HER2/neu Assays
  • 5.3.5 Iressa and Tarceva Companion Test
  • 5.3.6 Tykerb (GSK), and Vectibix (Amgen) Companion Tests
  • 5.3.7 EGFRx Assay
  • 5.3.8 Monogram eTag
  • 5.3.9 Veripath OncoDiagnostics EGFR PharmDX
  • 5.3.10 NSCL Patients with EGFR Mutation
  • 5.3.11 A Personalized Medicine Program for Chronic Myeloid Leukemia
• 5.4 Companions Based on Myriad' s IVDMIA Technology
  • 5.4.1 Myriad' s TheraGuide 5-FU
  • 5.4.2 Myriad' s BRCA Companion Dx Testing for BioMarin' s PARP Inhibitor BMN 673
• 5.5 Companions for Tyrosine Kinase Inhibitors: Erlotinib and Gefitinib
  • 5.5.1 TheraScreen: EGFR29
  • 5.5.2 The K-RAS Mutation Detection Kit
• 5.6 Irinotecan and UGT1A1
• 5.7 Gleevec (Imatinib) Companions
  • 5.7.1 DakoCytomation' s c-Kit (9.7) pharmDx
• 5.8 Companion Diagnostics Involving Metabolizing Enzymes
  • 5.8.1 Companions for TMPT, CYP2C9 and UGT1A1 Enzymes
  • 5.8.2 Companions for Aromatase Inhibitors
  • 5.8.3 Companions for Actos and Avandia
• 5.9 Drivers and Barriers to Companion Diagnostics
• 5.10 Partnerships with Pharma Companies to Identify Therapeutic Targets
• 5.11 Circulating Tumor Cell Assay: Prognostic and Predictive Factors for Breast Cancer
• 5.12 Companion Diagnostics Used by Clinical Service Laboratories
• 5.13 New Technologies and Products under Development
  • 5.13.1 OncoMethylome
• 5.14 Pharmacogenomics Tests
  • 5.14.1 MGMT Methylation Assay
  • 5.14.2 Other Pharmacogenomic Opportunities
• 5.15 Recurrence Prediction Tests
• 5.16 Blood-based Technologies
  • 5.16.1 Oncotech
• 5.17 Monogram Biosciences HIV Personalized Platform
• 5.18 Wako LBA¥AFP Test for Liver Cancer
• 5.19 Future Developments for Companion Diagnostics
• 5.20 Drug Response Predictors

6. Business and Regulatory Trends in the Companion Biomarker Testing Sector

• 6.1 Industry Consolidation
• 6.2 Breath of Product Offering and Pricing
• 6.3 Government Regulation of Medical Devices
  • 6.3.1 FDA Guidance on Drug Test Co-development
  • 6.3.2 Device Classes
  • 6.3.3 Investigational Use of IVDM Assays
  • 6.3.4 Post-market Requirements
  • 6.3.5 Voluntary versus Required Submissions
  • 6.3.6 Examples of Recent Voluntary Genomic Data Submissions
  • 6.3.7 FDA Labeling Implications and Rules
  • 6.3.8 Regulatory Activities in Companion Diagnostic Testing-Translation of Diagnostic Testing Results into Clinical Practice
• 6.4 Strategic Business and Marketing Considerations
• 6.5 Commercial Opportunities in Companion Markers
• 6.6 Moderators of Growth
  • 6.6.1 Roadblocks to Integrating Companion Biomarkers into Clinical Practice
  • 6.6.2 Management of Targeted Therapeutics by Third-Party Payers
• 6.7 Biotechnology Industry Trends
• 6.8 Pharmaceutical Industry Trends
• 6.9 Acquisition, License Agreement, Partnerships
• 6.10 Legal Developments
• 6.11 Sales and Marketing Strategies for Tumor Marker Tests
  • 6.11.1 International Markets
  • 6.11.2 Europe
  • 6.11.3 Central and South America
  • 6.11.4 Asia-Pacific
• 6.12 Product Commercialization
• 6.13 Reimbursement
• 6.14 Self-Referral Rules
• 6.15 Health Insurance Portability and Accountability Act
• 6.16 Clinical Laboratory Improvement Amendments (CLIA)
• 6.17 In Vitro Diagnostic Directive (IVDD) and Medical Device Regulations
• 6.18 FDA' s Quality System Regulation (QSR)
• 6.19 FDA' S OIVD on IVDMIAs
• 6.20 FDA' s Qualification of Cancer Biomarkers
  • 6.20.1 Regulatory Perspectives of Biomarker Validation
• 6.21 Genetic Tests and Medical Records
  • 6.21.1 Laws against Genetic Discrimination
• 6.22 Global Drivers of Clinical Laboratory Testing
• 6.23 Global Outlook
• 6.24 Oncology Biomarker Qualification Initiative
• 6.25 FDA Critical Path
  • 6.25.1 Examples of Drugs being held up due to lack of Compliance with FDA Directives
• 6.26 Biomarkers and FDA' s Voluntary Genomic Data Submission
• 6.27 From Personalized to Predictive Medicine
• 6.28 Analysis of Cost-Effectiveness at the Individual Level
• 6.29 The Patient and Advocate Perspective: An Evolution of Influence
• 6.30 Real-World Experiences Translating the Vision of Personalized Medicine into Practice
  • 6.30.1 Evolving Business Models in Companion Dx and Personalized Medicine
  • 6.30.2 Current Pharm/Dx Business Model Examples
• 6.31 Reimbursement and Value Creation
• 6.32 What is the Role of Governmental Agencies in Driving the Adoption of CDx?
• 6.33 What is the Role of the Insurance Industry in Driving the Adoption PGx?
• 6.34 What is the Role of the Pharma Industry in Driving the Adoption of PGx?
• 6.35 FDA Guidance Document on Co-development
• 6.36 What is the Role of the Diagnostic Industry in Driving the Adoption of PGx?
• 6.37 What is the Future Role of PBM' s in Laboratory Services?

7. Companies Entering the Companion Diagnostics Market

• 7.1 Industry Overview
  • 7.1.1 20/20 GeneSystems, Inc.
  • 7.1.2 Abbott Diagnostics
  • 7.1.3 Affymetrix
  • 7.1.4 Agendia BV
  • 7.1.5 Agensys, Inc.
  • 7.1.6 Almac Group
  • 7.1.7 Almac Diagnostics
  • 7.1.8 AMDL, Inc.
  • 7.1.9 Arcturus Bioscience, Inc. (Acquired by Molecular Devices)
  • 7.1.10 Aureon Laboratories Corporation
  • 7.1.11 Becton, Dickinson and Company
  • 7.1.12 Beckman Coulter, Inc.
  • 7.1.13 Biocode Hycel
  • 7.1.14 BioCurex, Inc.
  • 7.1.15 Biodesix
  • 7.1.16 Biomarker Technologies, LLC
  • 7.1.17 Biomedical Diagnostics, LLC
  • 7.1.18 Biomerica
  • 7.1.19 bioMerieux
  • 7.1.20 BioModa, Inc.
  • 7.1.21 Bruker Daltonics
  • 7.1.22 Cangen Biotechnologies, Inc.
  • 7.1.23 Caprion Proteomics
  • 7.1.24 Celera Diagnostics
  • 7.1.25 Cepheid
  • 7.1.26 Claros Diagnostics
  • 7.1.27 Clinical Data, Inc.
  • 7.1.28 Ciphergen Biosystems, Inc. (Renamed Vermillion, Inc.)
  • 7.1.29 Clarient, Inc.
  • 7.1.30 Correlogic Systems, Inc.
  • 7.1.31 CytoCore, Inc.
  • 7.1.32 Cytogen Corporation
  • 7.1.33 Cytyc Corporation
  • 7.1.34 Dako (Formerly DakoCytomation)
  • 7.1.35 DiaDexus
  • 7.1.36 Digene (Acquired by Qiagen)
  • 7.1.37 DiagnoCure
  • 7.1.38 Diagnostic Systems Laboratories, Inc. (Acquired by Beckman Coulter)
  • 7.1.39 DRG International
  • 7.1.40 DxS (Acquired by Qiagen)
  • 7.1.41 EDP Biotech Corporation
  • 7.1.42 Epigenomics
  • 7.1.43 EXACT Sciences Corporation
  • 7.1.44 Exagen Diagnostics
  • 7.1.45 Gene Logic, Inc.
  • 7.1.46 Genesis Genomics, Inc.
  • 7.1.47 Genomic Health
  • 7.1.48 Gen-Probe, Inc.
  • 7.1.49 Health Discovery Corporation
  • 7.1.50 Ikonisys, Inc.
  • 7.1.51 Immunicon Corporation
  • 7.1.52 Immunomedics
  • 7.1.53 Incyte
  • 7.1.54 InterGenetics
  • 7.1.55 Ipsogen
  • 7.1.56 Johnson & Johnson
  • 7.1.57 LabCorp
  • 7.1.58 Matritech, Inc.
  • 7.1.59 Miraculins
  • 7.1.60 Mitsubishi Kagaku latron
  • 7.1.61 Monogram Biosciences
  • 7.1.62 Myriad Genetics, Inc.
  • 7.1.63 NimbleGen Systems
  • 7.1.64 Northwest Biotherapeutics, Inc.
  • 7.1.65 Nycomed
  • 7.1.66 Oncotech, Inc.
  • 7.1.67 Oncothyreon (Formerly known as Biomira)
  • 7.1.68 Orion Genomics
  • 7.1.69 Oxford Genome Sciences
  • 7.1.70 Panacea Pharmaceuticals, Inc.
  • 7.1.71 Perlegen Sciences, Inc.
  • 7.1.72 Polymedco, Inc.
  • 7.1.73 Power3 Medical Products
  • 7.1.74 Prometheus
  • 7.1.75 Proteome Systems Limited
  • 7.1.76 Qiagen N.V.
  • 7.1.77 Sanko Junyaku Co. Ltd.
  • 7.1.78 SensiGen, LLC
  • 7.1.79 SuperArray Bioscience Corporation
  • 7.1.80 Third Wave Technologies, Inc.
  • 7.1.81 Tosoh Biosciences
  • 7.1.82 TrimGen
  • 7.1.83 Upstream Biosciences, Inc.
  • 7.1.84 Ventana Medical Systems, Inc.
  • 7.1.85 Veridex, LLC

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

• I. Introduction
• II. Background
• III. Submission Policy
  • A. General Principles
  • B. Specific Uses of Pharmacogenomic Data in Drug Development and Labeling
  • C. Benefits of Voluntary Submissions to Sponsors and FDA
• IV. Submission of Pharmacogenomic Data
  • A. Submission of Pharmacogenomic Data during the IND Phase
  • B. Submission of Pharmacogenomic Data to a New NDA, BLA, or Supplement
  • C. Submission to a Previously Approved NDA or BLA
  • D. Compliance with 21 CFR Part 58
  • E. Submission of Voluntary Genomic Data from Application-Independent Research
• V. Format and Content of a VGDS
• VI. Process for Submitting Pharmacogenomic Data
• VII. Agency Review of Voluntary Genomic Data Submissions

Glossary

Appendix 2: Histochemical Markers for Cancer

INDEX OF FIGURES

• Figure 2.1: Personalizing Drug Treatment
• Figure 2.2: Approaches to Personalized Medicine
• Figure 2.3: The Phase I and II Processes of Drug Metabolism
• Figure 2.4: Hepatic Distribution of Human CYP450
• Figure 2.5: Relative Contribution of CYP450 Enzymes to Drug Metabolism
• Figure 2.6: Genetic Components Determine Drug Metabolism
• Figure 2.7: Personalized Medicine Drugs in Development
• Figure 2.8: Healthcare Value Chain
• Figure 3.1: From Genetic Content to Personalized Medicine
• Figure 3.2: Impact of Diagnostic Testing on Healthcare Decision Making
• Figure 3.3: Impact of Diagnostic Testing on Healthcare Spending
• Figure 3.4: Breakout of the Molecular Diagnostics Marketplace by Country
• Figure 3.5: Breakout of the Molecular Diagnostics Marketplace by Vendor
• Figure 3.6: Molecular Diagnostics Market Segmentation
• Figure 3.7: Molecular Diagnostics Market Segmentation by Technology
• Figure 3.8: Market Survey Respondent Demographics
• Figure 3.9: Breakout of the Respondent Pool by Affiliation
• Figure 3.10: Segmentation of the Personalized Medicine Market
• Figure 4.1: Personalized Medicine Market Drivers
• Figure 4.2: Challenges in the Personalized Medicine Space
• Figure 5.1: Carcinogenesis is a Multi-Step Process
• Figure 5.2: ASCO-CAP Guidelines for HER2 Testing in Breast Cancer: Equivocal Results with IHC
• Figure 5.3: ASCO-CAP Guidelines for HER2 Testing in Breast Cancer: Results by FISH
• Figure 5.4: MGMT Methylation Status Correlates to Survival Rate

INDEX OF TABLES

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