1 Table of Contents
1 Table of Contents 5
1.1 List of Tables 8
1.2 List of Figures 9
2 Biomarkers in Drug Discovery - Introduction 10
2.1 Introduction 10
3 Biomarkers in Drug Discovery - Overview 11
3.1 History of Biomarkers 11
3.2 Biomarkers Cater to the Unmet Needs in Drug Discovery 13
3.2.1 High Attrition Rates 14
3.2.2 High Drug Discovery Cost 15
3.2.3 Time Consuming 15
3.2.4 Safety and Efficacy 15
3.2.5 Invasiveness, Selectivity and Sensitivity 15
3.3 Biomarker Discovery and the Validation Process 16
3.3.1 Discovery 16
3.3.2 Development 17
3.3.3 Launch 17
4 Biomarkers in Drug Discovery - Market Characterization 19
4.1 Market Size and Forecasts 19
4.2 Global Biomarkers Market – Geographic Landscape 20
4.2.1 Introduction 20
4.2.2 North America 20
4.2.3 Europe 20
4.2.4 Asia 21
4.2.5 Row 21
4.3 Drivers and Barriers 21
4.3.1 Drivers for the Global Biomarkers Market 22
4.3.2 Barriers for the Global Biomarkers Market 24
5 Biomarkers in Drug Discovery - Time Trends 25
5.1 Historic Trend 25
5.1.1 Predictions Based on Biomarkers 25
5.1.2 Validation Versus Qualification 25
5.1.3 Lack of Synergy between Mechanism and Pattern 25
5.1.4 Regulatory Approval of Biomarkers 26
5.1.5 Difference in Regulation of Single Biomarkers and Panel of Biomarkers 26
5.1.6 Measures of Success 26
5.2 Future Trend – Growing Demand for Personalized Medicine 27
5.2.1 Companion Diagnostics Market 27
5.2.2 Drivers and Barriers for Companion Diagnostics Market 28
5.2.3 Regulations of Companion Diagnostics – EU 28
5.2.4 Regulations of Companion Diagnostics – US 29
6 Biomarkers in Drug Discovery - Technologies Used for Biomarker Discovery 30
6.1 Role of Imaging as a Predictive Biomarker 30
6.2 Biomarker Discovery Using Proteomics via Mass Spectrometry 32
6.3 High-Throughput Proteome Screening for Biomarker Detection 34
7 Biomarkers in Drug Discovery - How Biomarker Development Relates to Drug Discovery 36
7.1 Application of Biomarkers in Drug Discovery 36
7.1.1 Lead Identification and Optimization 38
7.1.2 Potential Role of Biomarkers in Lead Identification and Optimization 39
7.1.3 Target Validation 39
7.1.4 Toxicological Assay (Preclinical and Clinical) 39
7.1.5 Mechanism of Action 40
7.1.6 Monitor Therapy and Dose Response 40
7.1.7 Stratify Patient Population 40
7.1.8 Filing and Post-Marketing Surveillance 41
7.2 Benefits of Biomarker Utilization 41
7.2.1 Disease Understanding 41
7.2.2 Project Prioritization through Early Attrition 41
7.2.3 Streamlining Clinical Trials 41
7.2.4 Reducing Cost of Drug Development 42
7.2.5 Expediting Drug Development 42
7.2.6 Avoiding Adverse Drug Reactions and Rationalizing Dosing Regimen 42
7.2.7 Drug Repositioning 42
7.3 Challenges in Biomarker Utilization 42
7.3.1 Variability 42
7.3.2 Validity 43
7.3.3 Measurement Errors 43
7.4 Biomarker Classification 44
7.4.1 Biomarker Categories 45
7.4.2 Types of Biomarkers 45
7.4.3 Reasons for Surrogate Endpoint ‘Failure’ 47
8 Biomarkers in Drug Discovery - Integration of Biomarkers in Different Phases of Drug Development 49
8.1 Discovery 50
8.1.1 Predictive Safety Biomarkers 50
8.1.2 Mechanism of Action Markers 50
8.2 Preclinical Development 50
8.2.1 Prognostic and Epidemiological Biomarkers 50
8.2.2 Diagnostic Biomarkers 51
8.3 Clinical Development 52
8.3.1 Disease Progression Markers or Response to Therapy Markers 52
8.3.2 Surrogate Biomarkers 52
9 Biomarkers in Drug Discovery - Case Study 53
9.1 Role of HER2 Gene in Herceptin Development for Breast Cancer 53
9.1.1 Activation of Antibody-Dependent Cellular Cytotoxicity 53
9.1.2 Prevention of the Formation of p95HER2 53
9.1.3 Inhibition of HER2-activated Cell Proliferation 54
9.1.4 Inhibition of HER2-regulated Angiogenesis 54
9.1.5 Herceptin Side Effects 55
9.2 Role of BCR-ABL Fusion Protein in Development of Gleevec for Chronic Myelogenous Leukemia 57
10 Biomarkers in Drug Discovery - Regulatory Trends 59
10.1 Regulatory Landscape 59
10.1.1 Investigative/Exploratory Biomarker 59
10.1.2 Probable Valid Biomarker 59
10.1.3 Known Valid Biomarker 59
10.1.4 Letter Of Intent to Propose Biomarker Qualification 59
10.1.5 Structure of Biomarker Qualification Briefing Document 60
10.2 Validated Biomarker 62
10.3 Regulatory Acceptance of Valid Biomarkers 65
10.4 Regulatory Guidance from the FDA, EMA and MHLW 65
11 Biomarkers in Drug Discovery - Promising Biomarkers 66
11.1 Biomarkers for Alzheimer’s Disease 66
11.1.1 Imaging Biomarkers 66
11.1.2 Fluid Biomarkers 67
11.2 Biomarkers for Cancer 67
11.2.1 Insulin-like Growth Factor 1 and 2 69
11.2.2 OVA1 69
11.2.3 Risk of Ovarian Malignancy Algorithm 69
11.2.4 Serum Markers 69
11.3 Biomarkers for Multiple Sclerosis 70
11.3.1 Serum Marker: Brain-Derived Neurotrophic Factor 70
11.3.2 Cerebrospinal Fluid Markers 70
11.3.3 Imaging Marker 71
11.4 Biomarkers for Rheumatoid Arthritis 71
11.4.1 Micro RNAs 71
11.4.2 Autoantibodies 72
11.4.3 Inflammatory Markers 72
11.5 Biomarkers for Hepatitis C 73
11.5.1 Serum Markers 73
11.5.2 Imaging Markers 73
11.5.3 Non-Structural 5A Protein 74
11.5.4 Micro RNA-22 74
12 Biomarkers in Drug Discovery - Strategic Consolidations 75
12.1 M&A Deals 75
12.1.1 Micromedic Buys 33% Stake in BioMarCare for $1m 75
12.1.2 ValiRx Plc Acquires Pharmatest’s Biomarkers Business Unit 75
12.1.3 David H. Murdock Research Institute Acquires the Immune Tolerance Institute 76
12.1.4 Health Diagnostic Laboratory Acquires Harris Scientific 76
12.1.5 Myriad Genetics Acquires Rules-based Medicine 76
12.2 Licensing Agreements 77
12.2.1 SomaLogic Enters into Licensing Agreement with AmberGen 77
12.2.2 Advion BioServices Enters into Licensing Agreement with SISCAPA Assay Services 77
12.2.3 AVEO Pharmaceuticals Enters into Licensing Agreement with Centocor Ortho Biotech 78
12.2.4 KineMed Extends Licensing Agreement with Bristol-Myers Squibb 78
12.3 Partnership Deals 79
12.3.1 KineMed Enters Multi-year Agreement with GlaxoSmithKline to Develop Kinetic Biomarkers 80
12.3.2 Affymetrix and Massachusetts General Hospital Seal Deal to Develop Cancer Biomarker Diagnostics 80
12.3.3 Genedata and Roche Extend Collaboration of Biomarker Discovery 80
12.3.4 Isogen Life Science Enters into Co-Marketing Agreement with Axela for Biomarker Analysis Platforms 80
13 Biomarkers in Drug Discovery - Appendix 81
13.1 Market Definitions 81
13.2 Abbreviations 81
13.3 Bibliography 83
13.4 Research Methodology 86
13.4.1 Coverage 86
13.4.2 Secondary Research 86
13.4.3 Primary Research 86
13.4.4 Expert Panel Validation 87
13.5 Contact Us 87
13.6 Disclaimer 87
1.1 List of Tables
Table 1: Biomarkers in Drug Discovery, Global, Biomarkers Qualified by EMA for Use in Drug Development, 2012 17
Table 2: Biomarkers in Drug Discovery, Global, Biomarkers Qualified by FDA for Use in Drug Development, 2012 18
Table 3: Biomarkers in Drug Discovery, Global Biomarker’s Market, Revenue ($bn), 2004–2011 19
Table 4: Biomarkers in Drug Discovery, Global Biomarker’s Market, Revenue Forecast ($bn), 2011–2018 19
Table 5: Biomarkers in Drug Discovery, Global, Biomarker Discovery by Mass Spectrometry, Problems and Solutions, 2012 33
Table 6: Biomarkers in Drug Discovery, Global, Examples of Biomarkers, 2012 47
Table 7: Biomarkers in Drug Discovery, Global, Herceptin Development Timeline, 2012 55
Table 8: Biomarkers in Drug Discovery, Global, Validated Biomarkers Applied in FDA-approved Drugs, 2012 62
Table 9: Biomarkers in Drug Discovery, Global, Imaging and Cerebrospinal Fluid Biomarker Categories in Alzheimer’s Disease, 2012 66
Table 10: Biomarkers in Drug Discovery, Global, Prognostic and Diagnostic Biomarkers for Cancer, 2012 68
Table 11: Biomarkers in Drug Discovery, Global, Micro RNAs as Biomarkers of Cancer, 2012 69
Table 12: Biomarkers in Drug Discovery, Global, Cerebrospinal Fluid Biomarkers in Multiple Sclerosis, 2012 70
Table 13: Biomarkers in Drug Discovery, Global, Micro RNA as Biomarker for Rheumatoid Arthritis, 2012 71
Table 14: Biomarkers in Drug Discovery, Global, Strategic Consolidations, Mergers and Acquisitions, 2011–2012 75
Table 15: Biomarkers in Drug Discovery, Global, Strategic Consolidations, Licensing Agreement Deals, 2011–2012 77
Table 16: Biomarkers in Drug Discovery, Global, Strategic Consolidations, Partnerships Deals, 2011–2012 79`
1.2 List of Figures
Figure 1: Biomarkers in Drug Discovery, Global, Commonly Identified Biomarkers, 2012 10
Figure 2: Biomarkers in Drug Discovery, Global, History of Biomarkers, 2012 11
Figure 3: Biomarkers in Drug Discovery, Global, Biomarkers Cater to the Unmet Needs of Conventional Drug Discovery Methods, 2012 13
Figure 4: Biomarkers in Drug Discovery, Global, Reasons for Attrition, 2012 14
Figure 5: Biomarkers in Drug Discovery, Global, Biomarker Discovery and Validation Process, 2012 16
Figure 6: Biomarkers in Drug Discovery, Global Biomarkers Market, Revenue Forecast ($bn), 2004–2018 19
Figure 7: Biomarkers in Drug Discovery, Global, Geographic Landscape – Global Biomarkers Market, 2012 20
Figure 8: Biomarkers in Drug Discovery, Global, Market Drivers and Restraints, 2012 21
Figure 9: Biomarkers in Drug Discovery, Global, Integration of ‘Omics’ Drives Global Biomarker Market, 2012 23
Figure 10: Biomarkers in Drug Discovery, Global, Roche, Companion Diagnostics Development Process, 2012 27
Figure 11: Biomarkers in Drug Discovery, Global, Diagnostic Criteria for Multiple Sclerosis, 2012 30
Figure 12: Biomarkers in Drug Discovery, Global, Case Study, 2012 31
Figure 13: Biomarkers in Drug Discovery, Global, Protein Identification by Mass Spectrometry, 2012 32
Figure 14: Biomarkers in Drug Discovery, Global, Peptide Identification by Tandem Mass Spectrometry, 2012 33
Figure 15: Biomarkers in Drug Discovery, Global, Biomarker Discovery – Equalizer Bead Fractionation and ProteinChip SELDI System, 2012 34
Figure 16: Biomarkers in Drug Discovery, Global, Biomarker Discovery – Fractionation Schemes, 2012 35
Figure 17: Biomarkers in Drug Discovery, Global, Biomarkers’ Development and Drug Development Comparison, 2012 36
Figure 18: Biomarkers in Drug Discovery, Global, Role of Biomarkers in Drug Discovery and Development, 2012 37
Figure 19: Biomarkers in Drug Discovery, Global, Drug Discovery Process, 2012 37
Figure 20: Biomarkers in Drug Discovery, Global, Biomarkers Accelerate the Drug Discovery Process, 2012 38
Figure 21: Biomarkers in Drug Discovery, Global, Adoption of Biomarkers by Top Companies in Drug Discovery, 2012 40
Figure 22: Biomarkers in Drug Discovery, Global, Biomarker Classification, Disease and Drug-related Biomarkers, 2012 44
Figure 23: Biomarkers in Drug Discovery, Global, Biomarker Categories, 2012 45
Figure 24: Biomarkers in Drug Discovery, Global, Types of Biomarkers, 2012 45
Figure 25: Biomarkers in Drug Discovery, Global, Reasons for Surrogate Endpoint Failure, 2012 47
Figure 26: Biomarkers in Drug Discovery, Global, Reasons for Surrogate Endpoint Failure, 2012 47
Figure 27: Biomarkers in Drug Discovery, Global, Reasons for Surrogate Endpoint Failure, 2012 48
Figure 28: Biomarkers in Drug Discovery, Global, Reasons for Surrogate Endpoint Failure, 2012 48
Figure 29: Biomarkers in Drug Discovery, Global, Reasons for Surrogate Endpoint Failure, 2012 48
Figure 30: Biomarkers in Drug Discovery, Global, Biomarker Application in Each Stage of the Drug Discovery Process, 2012 49
Figure 31: Biomarkers in Drug Discovery, Relationship Between Different Types of Biomarkers and New Molecular Entities, 2012 51
Figure 32: Biomarkers in Drug Discovery, Global, Gleevec Approval Fact Sheet, 2012 57
