2. Introduction
• A biomarker is “a characteristic that is objectively measured and
evaluated as an indicator of normal biological processes, pathogenic
processes, or pharmacologic responses to a therapeutic intervention.”
— US National Institutes of Health
• “A biomarker is a substance used as an indicator of a biologic state. It
is a characteristic that is objectively measured and evaluated as an
indicator of normal biologic processes, pathogenic processes, or
pharmacologic responses to a therapeutic intervention.”—Wikipedia
• Biomarkers make take the form of cellular characteristics, metabolites
(e.g. sugars, lipids and hormones), molecular variations, or physical
features (e.g., clinical symptoms) and are assessed accordingly, via
measurement, annotation, documents, and images.
• Increasingly, the discovery of novel biomarkers is closely associated
with the advances in molecular biology techniques that can be
accessed through analysis of DNA, RNA or proteins.
3. Introduction(cont)
• Clinical end point
A characteristic or variable that reflects how a patient feels,
functions or survives
• Surrogate Endpoint
A biomarker intended to substitute for a clinical endpoint. A
surrogate endpoint is expected to predict clinical benefit (or
harm, or lack of benefit) based on epidemiologic, therapeutic,
pathophysiologic or other scientific evidence
4. Introduction(cont)
We can discriminate four main types of molecular biomarkers:
• Genomic biomarkers: based on the analysis of DNA (deoxyribonucleic acid)
profiles, especially the analysis of SNPs (single nucleotide polymorphisms), i.e.
identification of punctual variations in genomic DNA.
• Transcriptomic biomarkers: based on the analysis of RNA expression
profiles.
• Proteomic biomarkers: based on the analysis of the protein profiles.
• Metabolomic biomarkers: based on the analysis of metabolites (metabolites
are the intermediates and products of metabolism).
5. Use of Biomarkers in Clinical
Medicine
• Diagnosis
• Tool for staging disease
• Indicator of disease status
• Predict and/or monitor clinical response to an intervention
6. Examples of Biomarkers in
Clinical Medicine
• Electrocardiogram
• PET brain image
• Serum chemistries
• Auto-antigens in blood
• Bone densitometric measurement
• Pulmonary function test
• Neonatal Apgar score
7. Use of Biomarkers in Early Drug
Development and Decision
Making
• Evaluate activity in animal models
• Bridge animal and human pharmacology via proof-of-
mechanism or other observations
• Evaluate safety in animal models
• Evaluate human safety early in development
8. Use of Biomarkers in Early Drug
Development and Decision
Making
• Evaluate activity in animal models
• Bridge animal and human pharmacology via proof-of-
mechanism or other observations
• Evaluate safety in animal models
• Evaluate human safety early in development
9. Examples of Biomarkers in Early
Drug Development
• Serum chemistries
• Cell surface protein expression
• Drug pharmacokinetic measurements
• Drug metabolizing isoenzyme phenotype
• Serum transaminases
• Genomic expression profile
• Drug distribution or receptor occupancy via imaging
10. Use of Biomarkers in Later Drug
Development and Decision
Making
• Evaluate dose-response and optimal regimen for desired
pharmacologic effect
• Use safety markers to determine dose-response for toxicity
• Determine role (if any) of differences in metabolism on above
•
11. Biomarkers in Later Clinical
Development
• Psychometric testing
• Pain scales
• Imaging studies
• Culture status (antimicrobials)
• Pulmonary function tests
• Serum chemistries
• Electrocardiogram
12. Selected Companies Working in
Biomarker-Related Drug and R&D
Affymetrix, Inc.
Agendia B.V.
Agilent Technologies, Inc., LSCA group
Applied Biosystems
BioSite, Inc.
Caliper Life Sciences, Inc.
Celera Group
Cepheid
CombiMatrix Corp (Acacia Research)
Dako A/S
diaDexus, Inc.
Epigenomics AG
Fluidigm Corporation
Gene Logic, Inc.
NimbleGen Systems, Inc.
Nymox Pharmaceutical Corporation
Orion Genomics LLC
Qiagen NV
Roche Molecular Diagnostics
GVK-BIO
