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Overview

In recent years, there have been concerted efforts to enhance the precision of disease diagnosis and monitoring as the hetrogeneity of conditions becomes increasingly understood. Targeting broad patient populations in a ‘one-pill-fits-all’ approach has begun to attract criticism, with the average efficacy of such drugs being estimated at 50% or less. In the current climate, biomarkers have emerged as key tools in the realisation of personalised medicine by characterizing specific diseases and treatment responses at the DNA, RNA, protein, or metabolite level.

The Convergence of Biomarkers and Diagnostics is a new report published by Business Insights that provides a detailed assessment of recent developments and future opportunities for biomarker companies in all major therapeutic areas. This report analyzes the markets for diagnostic biomarkers, including currently marketed products and products in development, and examines current trends in the discovery, validation and clinical application of biomarkers. Advances in biomarker detection technologies are profiled and the strategies of companies involved in biomarker discovery or diagnostic development are assessed. This report also forecasts growth in biomarker and diagnostic segments to 2012. Identifying the latest developments in diagnostic biomarkers, examining biomarker-related patent trends and benchmarking the strategies used to identify and validate novel biomarkers with this new report.

Key findings

• The biomarker market was worth $5.5bn in 2007 and is forecast to grow at a CAGR of 17.6% to $12.4b in 2012. Rapid growth in the cardiovascular segment will result in this area becoming the leading category by sales volume in 2012.
• Cancer has more biomarker patent claims than any other indication based on analysis from patent documents in the World Intellectual Property Organization (WIPO) database.
• A large number of cardiovascular-based biomarkers are under investigation for inclusion in multimarker panels, including those indicative of inflammation, plaque instability and rupture, thrombosis and ischemia.
• Genotyping tests (primarily for viral infections) are currently worth an estimated $104mn. Business Insights forecast that this will grow to $686m in 2012 to become the fastest growing segment in the biomarker market, with an CAGR of 45.8%.
• Specialist companies use a variety of strategies and technologies to discover and validate new diagnostic biomarkers, with many bioinformatics companies now supporting biomarker discovery.

Key questions answered

• What types of molecules can serve as diagnostic biomarkers?
• Which in-vitro biomarker detection platforms are currently available?
• Where has progress been most evident in cancer, CNS, Alzheimer’s and cardiovascular disease profiling?
• What are the latest developments in the search for new diagnostic biomarkers?
• Why are multimarker assays being developed?
• What is the outlook for the biomarker-based diagnostics market?

Key issues examined by this report

• Rise of omic technologies. There is growing interest in the application of high-throughput omic technologies to biomarker discovery. Recent advances have provided a large inventory of candidate DNA, RNA, and protein biomarkers with potential for risk assessment, screening, diagnosis, prognosis, and selection.
• Advances in diagnostics. Transcriptomic, proteomic and metabolomic profiling represents a revolutionary approach to molecular diagnostics. It is anticipated that proteomic profiling will result in better tests to diagnose HBV infection.
• Biomarker-based targeting. With increasing numbers of drugs failing when aimed at broad populations, biomarkers are being used to differentiate between patient groups. This will help pharma companies revive the fortunes of poor performing products and develop new targeted drugs.
• Multiple biomarkers. There is an growing consensus that multiple biomarkers convey the multi-dimensional nature of a disease state more accurately, with panels of biomarkers expected to become the norm in the future. Researchers are also increasingly turning to biomedical imaging as a tool to track disease progress and improve patient outcomes.

Top reasons to purchase this report

• Identify developments and opportunities in biomarker-based diagnostics across cancer, CNS, infectious and cardiovascular diseases.
• Review the technologies used in biomarker discovery and validation and those enabling the translation of biomarker discoveries into clinical assays.
• Identify the main segments of the biomarker-based diagnostics market and forecast market growth to 2012.
• Assess the strategies of companies who are active in biomarker discovery and diagnostic test development.

Table of Contents

Executive Summary 2
Overview of biomarker-based diagnostics 2
Biomarker discovery and validation 3
Opportunities in cancer 4
Opportunities in cardiovascular disease 6
Opportunities in other diseases 7
Market considerations and forecasts 8
Trends and opportunities 10

Chapter 1 Overview of biomarker-based diagnostics 12
Summary 12
Introduction 13
Information provided by biomarkers 14
DNA biomarkers 15
RNA biomarkers 15
Protein biomarkers 16
Metabolite biomarkers 16
Technologies for in vitro biomarker detection 17
Nucleic acid testing 18
Probe-based NAT 19
DNA microarrays 21
DNA methylation analysis 22
Gene expression analysis 23
Protein analysis 24
Immunoassays 24
Mass spectrometry 26
Multimarker diagnostic panels 27
Regulation of in vitro diagnostic tests 29
Europe 29
US 30
Guidance on pharmacogenomic data submission 32
Drug-diagnostic co-development concept paper 33
Draft guidance on multivariate analysis 33
In vivo biomarker diagnostics 37

Chapter 2 Biomarker discovery and validation 42
Summary 42
Introduction 43
Omics approaches 43
Genomics 44
Transcriptomics 46
Proteomics 46
Metabolomics 50
Other omics and systems biology 50
Streamlining biomarker validation 51
Case studies 54
BG Medicine 54
Caprion Proteomics 56
Clinical Data 57
Compugen 58
Digilab Peptidomics 59
Metabolon 60
Monarch LifeSciences 61
Pronota 62
Source MDx 63
Vermillion 64

Chapter 3 Opportunities in cancer 68
Summary 68
Background on cancer 69
Biomarker-based diagnostics 71
Targeted therapies and companion diagnostics 73
Tests based on DNA biomarkers 74
Tests based on RNA biomarkers 77
Tests based on protein biomarkers 78
Biomarkers in breast cancer 80
Susceptibility 80
Detection 81
Prognosis and selection for therapy 83
Chemotherapy 85
Tamoxifen 87
HER2-targeting treatments 88
Biomarkers in prostate cancer 90
Susceptibility 90
Detection 91
Classification, prognosis, and treatment 93
Biomarkers in colorectal cancer 94
Susceptibility 95
Detection 96
Classification, prognosis, and treatment 97
Biomarkers in lung cancer 100
Susceptibility 100
Detection 101
Classification, prognosis, and treatment 102
Biomarkers in ovarian cancer 104
Detection 104
Classification and prognosis 106

Chapter 4 Opportunities in cardiovascular diseases 110
Summary 110
Background on cardiovascular disease 111
Biomarker-based diagnostics 112
Tests based on protein biomarkers 113
Tests based on other biomarkers 116
Biomarkers in coronary artery disease 118
Lipid/lipoprotein biomarkers 119
Biomarkers of inflammation, plaque instability 121
Genetic biomarkers 124
Biomarkers from omic studies 127
Biomarkers in acute coronary syndromes 129
Biomarkers of necrosis 129
Other biomarkers 131
Biomarkers for risk stratification 132
Multimarker strategies 133
Biomarkers in congestive heart failure 136
Biomarkers of hemodynamic strain 136
Pharmacogenomic biomarkers 137
Biomarkers in stroke 138
Prediction of drug efficacy 140

Chapter 5 Opportunities in other diseases 144
Summary 144
Biomarkers in infectious diseases 145
Viral infections 147
HIV 147
Hepatitis viruses 149
HPV 151
Influenza and SARS 152
Bacterial infections 153
Chlamydia and gonorrhea 153
Mycobacteria 154
MRSA 155
Sepsis screening 156
Biomarkers in CNS disorders 157
Alzheimer’s disease 157
Other neurodegenerative disorders 161
Multiple sclerosis 163
Traumatic brain injury 164
Biomarkers of CNS drug efficacy 164
Biomarkers in diabetes and obesity 167
Type 1 diabetes 167
Obesity and type 2 diabetes 168

Chapter 6 Market considerations and forecasts 174
Summary 174
Introduction 175
Overview of the total pharmaceuticals market 175
Overview of the total in vitro diagnostics market 175
Outlook for the diagnostic biomarkers market 179
Cancer: immunoassays and microarrays 181
Cardiovascular disease: immunoassays 183
Infection biomarkers 184
Predisposition and pharmacogenomic tests 185

Chapter 7 Trends and opportunities 188
Summary 188
Prospects for omics-derived biomarkers 189
Genomic variants as biomarkers 190
Gene expression signatures as biomarkers 190
Proteomic patterns as biomarkers 191
Translating omic discoveries into immunoassays 192
Factors affecting acceptance of biomarkers 193
Prospects for companion diagnostics 194
Biomarkers patent survey 195

Chapter 8 Appendix 208
Research Methodology 208
Proteomic Cancer Biomarkers 208
Biomarkers of Cardiovascular Disease and Stroke 208
Index 254

List of Figures
Figure 4.1: Biomarkers of Acute Coronary Syndromes 134

List of Tables
Table 1.1: In Vitro Diagnostic Multivariate Index Assays – FDA Draft Guidance (July, 07) 34
Table 4.2: Further Biomarkers of Cardiovascular Disease and Stroke 116
Table 6.3: Worldwide In Vitro Diagnostic Sales by Country 2007-2012 ($m) 177
Table 6.4: Worldwide In Vitro Diagnostic Sales by Application 2007-12 ($m) 178
Table 6.5: Biomarker Markets by Application 2007-2012 ($m) 180
Table 6.6: Biomarker Markets by Geographical Region 2007-2012 ($m) 181
Table 7.7: Analysis of filling and publication dates for biomarker patents, 2000-2007 197
Table 7.8: Biomarker assignees with six or more patents 198
Table 7.9: Biomarker patents: technologies and applications 199
Table 7.10: Biomarker assignees with six or more patents 201
Table 7.11: Patent activity analysis for top four biomarker assignees, Part 1 204
Table 7.12: Patent activity analysis for top four biomarker assignees, Part 2 205
Table 8.13: High Priority Proteomic Cancer Biomarkers 209
Table 8.14: Other Proteomic Cancer Biomarkers 217
Table 8.15: Biomarkers of Cardiovascular Disease and Stroke 246