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Abstract

Expert guidance in managing discovery and development of disease-related biomarkers

This report focuses on disease-related biomarkers, those related to disease screening, prognosis, and stratification-more specifically, disease-related molecular biomarkers. Aspects covered include:

• Historical and contextual information
• Strategies and technologies currently used for biomarker discovery and development
• Progress in biomarker discovery and development in several disease areas
• Current and future roles of consortia in disease-related biomarker discovery and development
• Market-related considerations, including the role of various sectors, competitive activity, deal activity, and regulatory factors
• Two separate surveys of individuals in (1) the pharma and biopharma sectors, and (2) biomarker discovery and diagnostic sectors. Both surveys capture attitudes, intentions, and current practices of individuals at the forefront of disease-related biomarker discovery and development.
• Profiles of 44 companies active in disease-related biomarkers
• In-depth interviews with 7 disease-related biomarker experts

Biomarker discovery has grown dramatically during the past decade, driven by:

• The availability of powerful new "omics" technologies
• The increasing utilization of new and untested targets in pharma
• The opportunity to replace suboptimal in vitro diagnostic assays with improved biomarkers

Disease-related biomarkers are not a new phenomenon. Early examples include blood glucose for diabetes diagnosis and management and cholesterol for cardiovascular risk. However, introduction of DNA microarrays in the mid-1990s enabled a revolution in transcriptomics and triggered a major paradigm shift in the way life scientists approached research. Subsequently, metabolomics and metabonomics, applied mainly to safety-related biomarkers originally, began to turn to disease-related biomarkers.

Table of Contents

CHAPTER 1 INTRODUCTION

• 1.1. Biomarker Definitions
• 1.2. Types of Biomarkers
  • Drug Discovery View
    • Broader View of Biomarker Types
  • Diagnostic Industry View
• 1.3. Disease-Related Biomarkers
• 1.4. Biomarkers in Drug Discovery and Development
• 1.5. Organization of the Report

CHAPTER 2 TECHNOLOGIES FOR BIOMARKER DISCOVERY AND ANALYSIS

• 2.1. Sensitivity, Specificity, and Predictive Value of Biomarker Assays
• 2.2. Pregenomic Biomarkers and Technologies
  • Enzyme and Metabolite Assays
  • Immunodiagnostics
    • Enzyme Immunoassays
  • Molecular Diagnostics
    • Target Amplification: Polymerase Chain Reaction
    • Signal Amplification Methods
• 2.3. Postgenomic Biomarkers and Technologies
  • Transcriptomics
    • Positional DNA Microarrays
      • Affymetrix Technology Platform
      • NimbleGen Process for Microarray Production
      • CombiMatrix Microarrays
      • Agilent' s Synthesized Arrays
      • Other Companies in the Microarray Market
      • Low-Density Arrays for In Vitro Diagnostic Applications
    • Encoded Particle Arrays
      • Illumina' s Encoded Particle Technology
      • Luminex' s xMAP Bead Arrays
      • Meso Scale Discovery Multi-array Formats for Immunoassays
      • Pierce' s SearchLight Proteome Arrays
      • Invitrogen' s Encoded Bead Technology
      • High Throughput Genomics' Gene Expression Assays
  • Proteomics
    • Ciphergen' s Technology
      • Biomarker Discovery
      • Assay Development
    • 2D Gel Electrophoresis
    • Differential In-gel Electrophoresis
    • Mass Spectrometry in Biomarker Discovery and Validation
      • Sample Processing
    • Metabolomics
  • Analysis of Metabolites in Biological Specimens
    • Metabolite Profiling for Biomarker Discovery
    • Potential for Metabolomics in Discovery of
    • Disease-Related Biomarkers
      • Sidebar: Disease-Related Imaging Biomarkers

CHAPTER 3 BIOMARKER ADVANCES IN SPECIFIC THERAPEUTIC AREAS

• 3.1. Cancer
  • Noncommercial Biomarker Programs
    • Nucleic Acid Programs
    • Protein Programs
      • Role of Autoimmunity in Cancer
      • Protein Biomarkers for Astrocytomas
      • Protein Biomarkers for Ovarian Cancer
      • Use of SELDI-TOF to Detect Prostate Cancer
      • Serum Peptidomics for Cancer Detection
    • Metabolomics Programs
  • Commercial Biomarker Programs
    • Nucleic Acid Programs
      • Gene Expression Tests
      • ErbB2 Gene Assay for Breast Tumors
      • PCA3 mRNA Test for Prostate Cancer
      • DNA Methylation-Based Cancer Assays
      • Use of Genomic Signatures in Cancer Diagnosis
    • Protein Programs
      • Serum-Based Biomarkers
      • Semen Test for Detecting Prostate Cancer
      • Serum Protein Panels as Cancer Biomarkers
      • Other Programs for Cancer Biomarker Identification and Development
    • Metabolomics Programs
    • Summary
• 3.2. Neurological Diseases
  • Noncommercial Programs
    • Identification of Biomarkers for Schizophrenia
    • Identification of Biomarkers for Alzheimer' s Disease
    • Identification of Molecular and Imaging Biomarkers for Parkinson' s Disease
  • Commercial Programs
• 3.3. Cardiovascular and Metabolic Diseases
  • Noncommercial Programs
    • Detection of Biomarkers for Type 2 Diabetes
  • Commercial Programs
• 3.4. Autoimmune and Inflammatory Diseases
  • Noncommercial Programs
    • Biomarker Programs for Lupus Nephritis
    • Biomarker Programs for Other Inflammatory Diseases
  • Commercial Programs
    • Biomarker Programs for Arthritis
    • Biomarker Program for Inflammatory Bowel Disease
• 3.5. Other Diseases
  • Noncommercial Programs
  • Commercial Programs

CHAPTER 4 PRECOMMERCIAL BIOMARKER DEVELOPMENT

• 4.1. PhRMA/NIH/FDA Biomarkers Consortium
• 4.2. European Union 7th Framework Biomarkers Programme
• 4.3. Other Consortia
  • International Cancer Biomarker Consortium
  • NCI' s Early Detection Research Network
  • Oncology Biomarker Qualification Initiative
  • Clinical Plasma Profiling Consortium
  • High-Risk Plaque Initiative

CHAPTER 5 MARKET CONSIDERATIONS

• 5.1. Sector-Related Efforts in Biomarker Discovery and Development
  • Role of Academia
  • Role of Pharmaceutical and Biopharmaceutical Companies
    • Confounding Issues in Biomarker Discovery
    • Biomarkers as Surrogate Endpoints
  • Role of Biotechnology Companies Specializing in Biomarker
  • Discovery
  • Role of the Diagnostics Industry
  • Regulatory Considerations
    • FDA IVDMIA Guidance
    • Regulations on Home-brew Tests
• 5.2. Summary of Recommendations to Develop Biomarker-based Tools for Cancer
  • Methods, Tools, and Resources Needed to Discover and Develop Biomarkers
  • Guidelines, Standards, Oversight, and Incentives Needed for Biomarker Development
  • Methods and Processes Needed for Clinical Evaluation and Adoption
• 5.3. Limitations in Converting Biomarkers to In Vitro Diagnostics
  • Technological Issues
  • Population Issues
  • Regulatory Issues
• 5.4. Relevant Deals
• 5.5. Deal Analysis

CHAPTER 6 CHI INSIGHT PHARMA REPORTS - DISEASE BIOMARKERS SURVEY - MARCH 2007

• 6.1. Pharmaceutical and Biopharmaceutical Company Responses
• 6.2. Diagnostics and Biomarker Discovery Company Responses
• 6.3. Overall Conclusions

CHAPTER 7 INTERVIEWS WITH DISEASE-RELATED BIOMARKER EXPERTS

• Bruce McCreedy, PhD, Metabolon
• Mark Reynolds, PhD, Gen-Probe
• Stephen Naylor, PhD, Predictive Physiology and Medicine
• Mark Chandler, PhD, Biophysical Corporation, and Ralph McDade, PhD, Rules-Based Medicine
• Emanuel Petricoin III, MD, PhD, George Mason University
• Brian Edmonds, PhD, Eli Lilly
• Deborah Neff, Pathwork Diagnostics
• Metabolomics Programs
• Summary

APPENDIX COMPANY PROFILES

• Almac Diagnostics
• Applied NeuroSolutions
• AviaraDx
• BG Medicine
• Biomarker Science
• Cambridge Theranostics Ltd
• Caprion Proteomics
• Ciphergen Biosystems
• Compugen
• Cogenics (part of Clinical Data)
• CombiMatrix Molecular Diagnostics
• Correlogic Systems
• diaDexus
• Epigenomics
• GE Healthcare
• Genizon Bioscience
• Health Discovery Corporation
• IBEX Technologies
• Illumina
• Ipsogen
• Med BioGene
• Metabolon
• Monogram Biosciences
• OncoMethylome Sciences
• Orion Genomics
• Oxford Genome Sciences
• Pathway Diagnostics
• Pathwork Diagnostics
• Phenomenome Discoveries
• Power3 Medical Products
• PPD
• Predictive Biosciences
• Predictive Physiology and Medicine
• Progenika Biopharma
• Proteome Sciences
• Proteome Systems
• ProteoSys
• Randox
• Rules-Based Medicine
• sanofi-aventis
• SIRS-Lab GmbH
• Target Discovery
• Targeted Molecular Diagnostics
• XDx

References

Company Index with Web Addresses