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.
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
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).
USE OF BIOMARKERS IN CLINICALMEDICINE• Diagnosis• Tool for staging disease• Indicator of disease status• Predict and/or monitor clinical response to an intervention
EXAMPLES OF BIOMARKERS IN CLINICALMEDICINE • Electrocardiogram• PET brain image• Serum chemistries• Auto-antigens in blood• Bone densitometric measurement• Pulmonary function test• Neonatal Apgar score
USE OF BIOMARKERS IN EARLY DRUGDEVELOPMENT 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
EXAMPLES OF BIOMARKERS IN EARLY DRUGDEVELOPMENT• 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
USE OF BIOMARKERS IN LATER DRUGDEVELOPMENT 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
BIOMARKERS IN LATER CLINICALDEVELOPMENT Psychometric testing Pain scales Imaging studies Culture status (antimicrobials) Pulmonary function tests Serum chemistries Electrocardiogram
SELECTED COMPANIES WORKING INBIOMARKER-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
ONLINE BIOMARKER DATABASE GVK BIO Online Biomarker Database (GOBIOM) is a comprehensive biomarker database that provides information on Biochemical, Genomic, Imaging, Metabolite, Clinical Scoring scales and Cellular markers for 16 different therapeutic areas with its reported utilities like diagnosis, prognosis, monitoring disease progression, treatment response, surrogate, efficacy and toxicity. i.e it gives complete information with respect to a marker’s preclinical, clinical and analytical qualifications with every data point hyperlinked to a valid reference.