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Biomarkers in Drug Discovery Integration in Early Stage Promotes Use of Companion Diagnostics to Optimize Therapeutic Outcomes

GBI Research Report Guidance

GBIHC257MR / Published NOV 2012

© GBI Research. This is a licensed product and is not to be photocopied

GBI Research Report Guidance

The report provides in-depth analysis of biomarkers’ potential applications in the pharmaceutical drug discovery process.

Chapter three describes the history of biomarkers and how they fulfill the unmet needs of the conventional drug discovery process. It also discusses the biomarker discovery and validation process.

Chapter four describes the market for biomarkers in drug discovery along with revenue forecasts until 2018 and market drivers and barriers.

Chapter five analyses the key issues faced historically in the application of biomarkers and future developments expected in the industry.

Chapter six discusses important types of technology being used in the discovery of biomarkers, highlighting their impact over the biomarker discovery process.

Chapter seven evaluates the advantages and disadvantages of using biomarkers in the drug discovery process.

Chapter eight studies the integration of different types of biomarkers in each phase of the drug discovery and development process and how it has helped to reduce cost and time-to-market for clinical trials.

Chapter nine discusses two case studies for the application of biomarkers in the successful development of drugs for the treatment of two different types of cancer.

Chapter 10 describes current regulatory trends in the global biomarkers drug discovery market as well as FDA biomarker validation.

Chapter 11 provides detailed analysis of the most promising biomarkers expected to enter the market in the next couple of years for certain key therapies.

The final chapter discusses the strategic consolidations that have taken place within the global biomarkers market, including M&A and strategic partnerships among companies involved in the manufacturing of biomarkers for drug discovery and research.


© GBI Research. This is a licensed product and is not to be photocopied

Executive Summary

Executive Summary

Biomarkers Market Expects Significant Growth

The global biomarkers market is an established market that has seen substantial growth since 2004 due to factors such as improvements in technology and the creation of favorable regulatory norms for the application of biomarkers in drug discovery.

Biomarkers in Drug Discovery, Global Biomarkers Market, Revenue Forecast ($bn), 2004-2018

2004 2011 2018

Rev

enue

($bn

)

CAGR (2004–2011): XX%

CAGR (2011–2018): XX%

Source: GBI Research

The biomarkers market was valued at $XX billion in 2004 and increased to $XX billion in 2011 at a Compound Annual Growth Rate (CAGR) of XX%. The majority of revenue is generated through the application of biomarkers in the discovery, testing and prescription of oncology therapeutics, making it one of the biggest therapeutic areas. The other leading therapeutic areas are Central Nervous System (CNS) and Cardiovascular System (CVS) disorders.

Growing Emphasis on Personalized Medicine and Companion Diagnostics

Historically, drug R&D processes were shaped by the conventional symptom-based approach, which considered that if the majority of patients responded favorably to a particular drug, for those who showed some side effects an alternative treatment would be more effective. This approach was known as the ‘one-size-fits-all’ or ’blockbuster’ model and led to issues such as higher R&D costs, longer development timelines and narrow product portfolios. Additionally, higher attrition rates led to a decline in the number of products approved despite huge investments in R&D. This led to the emergence of personalized medicine that allow individual targeted treatments to be designed according to genetic codes, ensuring a reduction in drug discovery costs and attrition rates. Companion diagnostics also play an important role in the realization of personalized medicine, as they are assays (tests or measurements) intended to assist physicians when making treatment decisions for their patients.

The biomarkers market was valued at $XX billion in 2004 and increased to $XX billion in 2011 at a CAGR of XX%


Page 5 © GBI Research. This is a licensed product and is not to be photocopied

Table of Contents

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..........................................................12

3.2.1 High Attrition Rates..........................................................................................................14 3.2.2 High Drug Discovery Cost .................................................................................................14 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.......................................................................15 3.3.1 Discovery .........................................................................................................................16 3.3.2 Development ...................................................................................................................16 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 .........................................................................21 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 ..................................................................................25 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.....................................................26 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......................................................................28

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.................................................31 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



Table of Contents

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 .............................................................................40

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 ............................................................................................................................42 7.3.3 Measurement Errors ........................................................................................................43

7.4 Biomarker Classification...........................................................................................................43 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.................................................................................................................................49

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......................................................................................................50

8.3 Clinical Development ...............................................................................................................51 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...................................................................53 9.1.4 Inhibition of HER2-regulated Angiogenesis........................................................................54 9.1.5 Herceptin Side Effects.......................................................................................................54

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....................................................59

10.2 Validated Biomarker ................................................................................................................61 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



Table of Contents

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 ....................................................................................68 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 ...............................................................................................................70

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 .......................................................................................................72 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 ..............................................................................................................76 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 .......77 12.2.4 KineMed Extends Licensing Agreement with Bristol-Myers Squibb .....................................78

12.3 Partnership Deals.....................................................................................................................78 12.3.1 KineMed Enters Multi-year Agreement with GlaxoSmithKline to Develop Kinetic Biomarkers

........................................................................................................................................79 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 ............................................................................................................85

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



Table of Contents

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, 201271 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



Table of Contents

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



Biomarkers in Drug Discovery - Introduction

2 Biomarkers in Drug Discovery - Introduction

2.1 Introduction

According to the Food and Drug Administration (FDA), a biological marker or biomarker is defined as a characteristic that is objectively measured and evaluated as an indicator of normal biologic processes, pathogenic processes, or biological responses to a therapeutic intervention. It can define a physiologic, pathologic, or anatomic characteristic or measurement thought to relate to an aspect of normal or abnormal biologic function. Changes in biomarkers following treatment may predict or identify safety problems related to a drug candidate or reveal pharmacological activity expected to predict an eventual benefit from treatment. Biomarkers can also reduce uncertainty in drug development and evaluation by providing quantitative predictions about drug performance.

In general, biomarkers are available in the form of specific enzyme or hormone concentrations and genetic or phenotypic distributions. They work as pharmacodynamic indicators of the drug in a clinical study for drug discovery. Biomarkers are detectable, computable and quantifiable substances that change in response to a chemical/biological stimulus and are used to quantify Absorption, Distribution, Metabolism, Excretion and Toxicity (ADMET) properties to identify drug response in clinical studies.

The following figure lists some commonly identified biomarkers:

Figure 1: Biomarkers in Drug Discovery, Global, Commonly Identified Biomarkers, 2012

• Metabolites• Carbohydrates

• Steroids• Lipids

• Peptides• Proteins• Protein

complexes

• Organelles• Cells

Simple molecules

Macromolecules

Complex systems

• Patients

• Glucose• Cholesterol

• Triglycerides

• Insulin• Prostate specific antigen

• C-reactive protein• Hemoglobin (HbA,C)

• CD4+,T-cells• Platelets

• Clinicalphenotype


Prior to the application of biomarkers, the conventional drug discovery process (symptom-based) had various drawbacks such as high attrition rates, high costs and erroneous predictions of drug safety and efficiency. The integration of biomarkers has tried to address these issues and has made the process smoother and less costly. The symptom-based approach or the ‘one-size-fits-all’ or ‘blockbuster’ model is now starting to be replaced by personalized medicine that allows for the design of individual targeted treatment based on genetic codes.

Since 2004, the global biomarkers market has seen substantial growth due to factors such as improvements in technology and creation of favorable regulatory norms for application of biomarkers in drug discovery.

The conventional drug discovery process had various drawbacks such as high attrition rates, high costs and erroneous predictions of drug safety and efficiency



Biomarkers in Drug Discovery - Overview

3.2.1 High Attrition Rates

Figure 4: Biomarkers in Drug Discovery, Global, Reasons for Attrition, 2012

Formulation

Resources

Unknown

Market potential

Others

PK/ Bioavailability

Strategic

Clinical safetyClinical efficacy

Toxicity


The traditional drug discovery process was unable to predict drug failures in the early phases, which led to a high drug attrition rate and fewer approvals. As biomarkers became more integrated attrition rates fell by XX% due to correct predictions of drug responses in the early stages of discovery, rendering the process efficient, accurate and short. Additionally, the new processes use advanced technologies that can develop novel therapies faster.

With biomarker integration, attrition rates fell by XX% due to correct predictions of drug responses in the early stages of discovery



Biomarkers in Drug Discovery - Market Characterization

4 Biomarkers in Drug Discovery - Market Characterization

4.1 Market Size and Forecasts

The global biomarkers market has seen substantial growth since 2004, due to factors such as improvements in technology and the creation of favorable regulatory norms for the application of biomarkers in drug discovery. Having grown at a Compound Annual Growth Rate (CAGR) of XX%, the market was valued at $XX billion in 2011. The majority of revenue is generated through the application of biomarkers in the discovery, testing and prescription of oncology therapeutics, making it one of the biggest therapeutic areas. The other leading therapeutic areas are Central Nervous System (CNS) and Cardio Vascular System (CVS).

Figure 6: Biomarkers in Drug Discovery, Global Biomarkers Market, Revenue Forecast ($bn), 2004–2018

2004 2005 2006 2007 2008 2009 2010 2011 2012 2013 2014 2015 2016 2017 2018

Rev

enue

($bn

)

CAGR (2004–2011): XX%

CAGR (2011–2018): XX%


Table 3: Biomarkers in Drug Discovery, Global Biomarker’s Market, Revenue ($bn), 2004–2011

Year 2004 2005 2006 2007 2008 2009 2010 2011 CAGR (%)

Revenue


Table 4: Biomarkers in Drug Discovery, Global Biomarker’s Market, Revenue Forecast ($bn), 2011–2018

Year 2011 2012 2013 2014 2015 2016 2017 2018 CAGR (%)

Revenue


The biomarkers market was valued at $XX billion in 2004 and rose to $XX billion in 2011 at a CAGR of XX%. With the FDA’s support of the application of biomarkers in drug discovery, the market is expected to generate $XX billion in 2018 at a CAGR of XX% from 2011.

The market is expected to generate $XX billion in 2018 at a CAGR of XX% from 2011



Biomarkers in Drug Discovery – Appendix

13 Biomarkers in Drug Discovery - Appendix

13.1 Market Definitions

Biomarker: An indicator of biological state used to evaluate normal biological process, pathogenic process, or pharmacological response to a therapy.

Pharmacodynamics: The study of a drug’s effect on the body and MoA of the drug administered.

13.2 Abbreviations

2-PAGE: 2-dimensional PolyAcrylamide Gel Electrophorsis

2D: Two Dimensional

3D: Three Dimensional

AD: Alzheimer’s Disease

ADCC: Antibody-Dependent Cellular Cytotoxicity

ADMET: Absorption, Distribution, Metabolism, Excretion and Toxicity

ALT: Alanine Aminotransferase

AST: Aspartate Aminotransferase

ATP: Adenosine Triphosphate

BCR-ABL: Breakpoint Cluster Region-Abelson

BLA: Biologics License Application

BMS: Bristol-Myers Squibb

CAGR: Compound Annual Growth Rate

CDER: Center for Drug Evaluation and Research

CHAPS: Cholamidopropyl Dimethylammonio Propanesulfonate

CHDH: Choline Dehydrogenase

CIS: Clinically Isolated Syndrome

CLIA: Clinical Laboratory Improvement Amendments

CML: Chronic Myelogenous Leukemia

cMRI: conventional Magnetic Resonance Imaging

CNS: Central Nervous System

CSF: Cerebrospinal Fluid

CT: Computed Tomography

CVS: Cardiovascular System

DHMRI: David H. Murdock Research Institute

DNA: Deoxyribonucleic Acid

EGFR: Epidermal Growth Factor Receptor

ELISA: Enzyme-Linked Immunosorbent Assay

EMA: European Medicines Agency

ESR: Erythrocyte Sedimentation Rate

FDA: Food and Drug Administration

FDG: Fluorodeoxyglucose




FGFR: Fibroblast Growth Factor Receptor

GD: Gadolinium

GHTF: Global Harmonization Task Force

GSK: GlaxoSmithKline

HAART: Highly Active Antiretroviral Therapy

HCV: Hepatitis C Virus

HDL: Health Diagnostic Laboratory

HE: Human Epididymis

HEPES: Hydroxyethyl Piperazine Ethanesulfonic Acid

HER: Human Epidermal Growth Factor Receptor

HESI: Health and Environmental Sciences Institute

HIV: Human Immunodeficiency Virus

HOXB13: Homeobox B13

HTLV: Human T-Lymphotropic Virus

IGFR: Insulin-Like Growth Factor Receptor

IL: Interleukin

ILS: Isogen Life Science

ILSI: International Life Sciences Institute

IND: Investigational New Drug

IVD: In Vitro Diagnostic

IVDMIA: In Vitro Diagnostic Multivariate Index Assay

LDT: Laboratory-Developed Tests

LOI: Letter Of Intent

MAPK: Mitogen-Activated Protein Kinase

MARVEL: Marker Validation for Erlotinib in Lung Cancer

MCI: Mild Cognitive Impairment

MoA: Mechanism of Action

MRE: Magnetic Resonance Elastography

MRI: Magnetic Resonance Imaging

MS: Multiple Sclerosis

NABT: Normal Appearing Brain Tissues

NCCTG: North Central Cancer Treatment Group

NDA: New Drug Application

NIA: National Institute on Aging

NK: Natural Killer

NS5A: Non-Structural 5A

NWG: Nephrotoxicity Working Group

OIVD: Office of In Vitro Diagnostic Device




PARP 1: Poly [ADP-ribose] polymerase 1

PCR: Polymerase Chain Reaction

PET: Positron Emission Tomography

PI3K: Phosphoinositide 3-Kinase

PMA: Premarket Approval

PSA: Prostate-Specific Antigen

PSTC: Predictive Safety and Testing Consortium

PTM: Post-Translational Modifications

RA: Rheumatoid Arthritis

RBM: Rules-Based Medicine

RF: Rheumatoid Factor

RNA: Ribonucleic Acid

ROMA: Risk of Ovarian Malignancy Algorithm

RON: Recepteur d’Origine Nantais

SAR: Structure Activity Relationship

SELDI-MS: Surface-Enhanced Laser Desorption/Ionization-Mass Spectrometry

SNP: Single Nucleotide Polymorphism

TE: Transient Elastography

TFA: Trifluoroacetic Acid

TNF: Tumor Necrosis Factor

VEP: Visual Evoked Potential

vMRI: Volumetric Magnetic Resonance Imaging

13.3 Bibliography

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Alzheimer’s Association (2012). Basics of Alzheimer’s disease. Available from: http://www.alz.org/national/documents/brochure_basicsofalz_low.pdf.

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Arnould L, et al. (2006). Trastuzumab-based treatment of HER2-positive breast cancer: an antibody-dependent cellular cytotoxicity mechanism? British Journal of Cancer; 94(2): 259-267.

Atkinson A, et al. (2001). Biomarkers and surrogate endpoints. Preferred Definitions and conceptual framework. Clinical Pharmacology and Therapeutics; 69: 89-95.

Baselga J, et al. (1996). Phase II study of weekly intravenous recombinant humanized anti-p185HER2 monoclonal antibody in patients with HER2/neu-overexpressing metastatic breast cancer. Journal of Clinical Oncology, 14(3): 737-744.

Bhatt AN, et al. (2010). Cancer biomarkers - Current perspectives. Indian Journal of Medical Research, 132: 129-149.




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Bulman A, et al. (2007). High-Throughput Methods for “Deep Proteome” Analyses for Biomarker Discovery Through Equalizer Bead Fractionation and the ProteinChip SELDI System. Bio-rad. Available from: http://www.expressionproteomics.com/pdf/07-0145_US_HUPO3_pstr.FINAL2.pdf.

Castera L, et al. (2005). Prospective comparison of transient elastography, Fibrotest, APRI, and liver biopsy for the assessment of fibrosis in chronic hepatitis C. Gastroenterology, 128(2): 343–350.

Charles River Laboratories International, Inc. (2009) The Role of Biomarkers in Drug Discovery and Development. Available from: http://www.criver.com/SiteCollectionDocuments/pc_d_role_of_biomarkers_in_drug_development.pdf.

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13.4 Research Methodology

GBI Research’s dedicated research and analysis teams consist of experienced professionals with a pedigree in marketing, market research, consulting backgrounds in the medical devices industry and advanced statistical expertise.

GBI Research adheres to the codes of practice of the Market Research Society (www.mrs.org.uk) and the Strategic and Competitive Intelligence Professionals (www.scip.org).

All GBI Research databases are continuously updated and revised. The following research methodology is followed for all databases and reports.

13.4.1 Coverage

The objective of updating GBI Research’s coverage is to ensure that it represents the most up-to-date vision of the industry possible.

Changes to the industry taxonomy are built on the basis of extensive research of company, association and competitor sources.

GBI Research aims to cover all major news events and deals in the medical industry, updated on a daily basis. The coverage is further streamlined and strengthened with additional inputs from GBI Research’s expert panel (see below).

13.4.2 Secondary Research

Secondary research was carried out on internal and external sources to obtain qualitative and quantitative information in the report.

The secondary research sources that are referred to in this report include but are not limited to:

Company websites, annual reports, financial reports, investor presentations and SEC Securities and Exchanges Commission filings.

Industry trade journals, scientific journals and other technical literature.

Relevant patent and regulatory databases.

National government documents, statistical databases and market reports.

News articles, press releases and webcasts specific to the companies operating in the market.

13.4.3 Primary Research

GBI Research conducts hundreds of primary interviews each year with industry participants and commentators in order to validate its data and analysis. A typical research interview fulfills the following functions:

It provides first-hand information on the market size, market trends, growth trends, competitive landscape, future outlook

Helps in validating and strengthening the secondary research findings; and

Further develops the analysis team’s expertise and market understanding.

Primary research involves email correspondence and telephone interviews, as well as face-to-face interviews for each market, category, segment and sub-segment across geographies.

The participants who typically take part in such a process include, but are not limited to:

Industry participants: CEOs, VPs, marketing/product managers, market intelligence managers and national sales managers;

Hospital stores, laboratories, pharmacies, distributors and paramedics;

Outside experts: investment bankers, valuation experts, research analysts specializing in specific medical equipment markets; and




Key Opinion Leaders: physicians and surgeons specializing in different therapeutic areas corresponding to different kinds of pharmaceutical drugs.

13.4.4 Expert Panel Validation

GBI Research uses a panel of experts to cross-verify its databases and forecasts.

GBI Research’s expert panel comprises marketing managers, product specialists, international sales managers from medical device companies, academics from research universities, KOLs from hospitals, consultants from venture capital funds and distributors/suppliers of medical equipment and supplies.

Historic data and forecasts are relayed to GBI Research’s expert panel for feedback and adjusted in accordance with their feedback.

13.6 Disclaimer

All Rights Reserved.

No part of this publication may be reproduced, stored in a retrieval system or transmitted in any form by any means; electronic, mechanical, photocopying, recording or otherwise, without the prior permission of the publisher, GBI Research.