Molecular Diagnostics: Transforming The Pharmaceuticals Market.

Molecular Diagnostics: Transforming The Pharmaceuticals Market.

Publisher:	D&MD Publications Inc
Year of publication:	2002
Type of publication:	Management report
Publisher's reference (if any):	D&MD9081
Author(s):	Sreten Bogdanovic and Beata Langlands
Approximate page count:	280
Price when published:	$4,950
Remarks: Page numbers, where given, refer to the draft manuscript (which may differ from the published version). The copyright in this report is owned by the publisher, to whom any requests for copies should be addressed. The price shown is for a single copy of the print version. Multiple copies and electronic copies usually have different prices.
MOLECULAR DIAGNOSTICS: TRANSFORMING THE PHARMACEUTICALS MARKET TABLE OF CONTENTS EXECUTIVE SUMMARY CHAPTER 1 INTRODUCTION 1.1 Overview of the IVD industry 1.1.1 IVD technology segments 1.1.2 Customers for IVD products 1.1.2.1 Clinical laboratory market 1.1.2.2 Point-of-care market 1.1.2.3 Over-the-counter market 1.2 Traditional in vitro diagnostics 1.3 Molecular diagnostics 1.4 Platform technologies for molecular diagnostics 1.4.1 Rapid immunoassays 1.4.2 Nucleic acid testing (NAT) 1.4.3 Biochips 1.5 Uses of traditional IVDs in clinical settings 1.5.1 Unique uses of molecular diagnostics 1.6 Diagnostic kits and homebrew tests Chapter 2 Technology developments 2.1 Immunoassay technology 2.1.1 Introduction 2.1.2 Principles and terms 2.1.3 Standardization 2.1.4 Immunoassay design 2.1.4.1 Competitive assays 2.1.4.2 Noncompetitive "sandwich" assays 2.1.5 Point-of-care immunoassays 2.1.5.1 Chromatographic lateral flow devices 2.1.6 Protein chips 2.1.6.1 Miniaturization of immunoassays 2.2 Nucleic acid testing technology 2.2.1 Introduction 2.2.2 Principles and terms 2.2.3 DNA probes and their uses 2.2.4 Nucleic acid amplification techniques 2.2.4.1 Target amplification 2.2.4.2 Signal amplification 2.2.5 DNA chips and miniaturization 2.2.5.1 DNA microarrays 2.2.5.2 Microfluidic devices 2.2.6 Genotyping methods 2.2.6.1 Use of DNA sequencers 2.2.6.2 Use of microarrays 2.2.7 Evolution of rapid point-of-care formats CHAPTER 3 MOLECULAR DIAGNOSTICS FOR COMMUNICABLE DISEASES 3.1 Introduction 3.2 Immunodiagnostic tests 3.2.1 Introduction 3.2.2 Rapid immunoassays 3.3 Nucleic acid tests 3.3.1 Introduction 3.3.2 Tests for viruses 3.3.2.1 HIV viral load and drug resistance 2.3.2.2 HBV/HCV viral load and drug resistance 3.3.2.3 CMV 3.3.2.4 HPV 3.3.2.5 Other viruses 3.3.3 Blood testing for viruses 3.3.4 Tests for bacteria 3.3.4.1 Chlamydia and gonorrhea 3.3.4.2 Mycobacteria 3.3.4.3 Other bacteria 3.3.4.4 Detection of antibiotic resistance 3.3.5 Tests for fungi and parasites CHAPTER 4 MOLECULAR DIAGNOSTICS FOR CARDIOLOGY 4.1 Introduction 4.1.1 Coronary Artery Disease 4.1.1.1 Risk factors 4.1.2 Myocardial infarction (MI) 4.1.2.1 Diagnosis 4.1.3 Congestive Heart Failure (CHF). 4.1.3.1 Diagnosis 4.2 Immunodiagnostic tests 4.2.1 Cardiovascular risk assessment tests 4.2.1.1 Homocysteine 4.2.1.2 C-Reactive Protein 4.2.1.3 Autoantibodies to oxidised LDL 4.2.1.4 Apolipoprotein B 4.2.1.5 Lipoprotein-associated phospholipase A2 4.2.1.6 Other biomarkers of potential value 4.2.2 Early detection of MI 4.2.2.1 The cardiac troponins T and I 4.2.2.2 Other cardiac markers 4.2.3 Early diagnosis of CHF 4.2.3.1 B-type natriuretic peptide 4.3 NAT-based tests 4.3.1 Genes and cardiovascular disease 4.3.2 Predictive tests on the market 4.3.3 Predictive tests under commercial development CHAPTER 5 MOLECULAR DIAGNOSTICS FOR ONCOLOGY 5.1 Introduction 5.1.1 Overview of cancer 5.1.1.1 Importance of early detection 5.1.2 Diagnosis 5.2 Immunodiagnostic tests 5.2.1 Introduction to tumor markers 5.2.2 Leading circulating tumor markers 5.2.2.1 PSA and cPSA 5.2.2.2 CA 125, CA 15-3, CA 19-9 5.2.2.3 CEA 5.2.2.4 AFP, HCG 5.2.2.5 VEGF 5.2.3 Novel circulating biomarkers 5.2.3.1 Kallikreins 5.2.3.2 Cancer-specific antibodies 5.2.4 Leading urine biomarkers 5.2.4.1 BTA stat test 5.2.4.2 NMP22 test 5.2.4.3 Accu-Dx test 5.2.4.4 Other potential urine biomarkers 5.2.5 New biomarker discovery 5.2.6 Theranostic tests 5.3 Nucleic acid tests 5.3.1 FISH-based tests 5.3.2 Predisposition tests based on sequencing 5.3.2.1 Hereditary breast cancer 5.3.2.2 Hereditary colorectal cancer 5.3.2.3 Hereditary kidney cancer 5.3.3 Detection of early-stage cancer 5.3.3.1 DNA in tumor cells 5.3.3.2 Circulating tumor nucleic acids 5.3.3.3 Tumor DNA in stool 5.3.3.4 Tumor DNA in urine 5.3.4 Detection of specific tumor markers 5.3.5 Theranostic tests 5.4 The promise of molecular signatures CHAPTER 6 MOLECULAR DIAGNOSTICS FOR MISCELLANEOUS CONDITIONS 6.1 Immunodiagnostic tests 6.1.1 Prenatal diagnosis 6.1.2 Drugs of abuse 6.1.3 Alzheimer's disease 6.1.4 Diabetes mellitus 6.1.5 Bone turnover 6.1.6 Assessment of oxidative stress 6.2 NAT-based assays 6.2.1 Overview 6.2.2 Screening for common monogenic diseases 6.2.2.1 Hemochromatosis 6.2.2.2 Cystic fibrosis 6.2.3 Prenatal and pre-implantation diagnosis 6.2.3.1 FISH-based tests on fetal cells 6.2.3.2 Fetal DNA testing 6.2.4 Other applications of DNA diagnostics 6.2.4.1 Alzheimer's disease 6.2.4.2 Organ transplantation 6.2.4.3 Identity testing 6.2.4.4 Posttrauma monitoring 6.2.5 Genetic susceptibility tests 6.2.5.1 Risk for periodontal disease 6.2.5.2 Risk for osteoporosis 6.2.5.3 Risk for complications from diabetes 6.2.5.4 Type 1 diabetes 6.2.6 Theranostic tests 6.2.6.1 Prediction of drug toxicity 6.2.6.2 Cholinomimetics (Alzheimer's disease) 6.2.6.3 Albuterol (asthma) 6.2.6.4 Rheumatoid arthritis therapy 6.2.6.5 Clozapine (schizophrenia) CHAPTER 7 BIOTERRORISM AND MOLECULAR DIAGNOSTICS 7.1 Introduction 7.1.1 Biological warfare agents (BWAs) 7.1.2 US government initiatives 7.1.3 IVD industry and bioterrorism preparedness 7.2 Anthrax and other BWAs in the environment 7.2.1 Rapid lateral flow immunoassays 7.2.2 Biosensors 7.2.2.1 Immunosensors 7.2.2.2 Synthetic receptor-based sensors 7.2.2.3 DNA sensors 7.2.2.4 Reagentless sensors 7.3 Anthrax in clinical samples 7.3.1 Traditional laboratory diagnosis 7.3.2 Rapid diagnostic tests 7.2.3.1 PCR-based laboratory tests 7.2.3.2 Rapid immunoassays 7.4 Developments in biochips CHAPTER 8 MARKET CONSIDERATIONS AND FORECASTS 8.1 Overview of the major world IVD markets 8.1.1 Global population growth 8.1.2 The US market 8.1.2.1 Health and healthcare 8.1.2.2 The market for IVD products 8.1.2.3 Regulation of IVD products 8.1.3 The Japanese market 8.1.3.1 Health and healthcare 8.1.3.2 The market for IVD products 8.1.3.3 Regulation of IVD products 8.1.4 The European market 8.1.4.1 EC-wide regulation of IVD products 8.1.5 Germany 8.1.5.1 Health and healthcare 8.1.5.2 The market for IVD products 8.1.6 Italy 8.1.6.1 Health and healthcare 8.1.6.2 The market for IVD products 8.1.7 France 8.1.7.1 Health and healthcare 8.1.7.2 The market for IVD products 8.1.8 Spain 8.1.8.1 Health and healthcare 8.1.8.2 The market for IVD products 8.1.9 United Kingdom 8.1.9.1 Health and healthcare 8.1.9.2 The market for IVD products 8.1.10 Emerging IVD markets 8.2 Market forecasts 8.2.1 IVD sales and forecasts by country 8.2.2 Oulook for the total immunoassay market 8.2.3 Outlook for the total NAT market 8.2.4 Forecasts for molecular diagnostics 8.2.4.1 Forecasts by application 8.2.4.2 Forecasts by geographical region CHAPTER 9 COMPANY PROFILES 9.0 Introduction 9.1 Abbott Laboratories Inc 9.2 AmpliStar 9.3 Bayer AG 9.4 Biopixel Ltd 9.5 Biosite Diagnostics Inc 9.6 Cepheid 9.7 Chembio Diagnostic Systems Inc 9.8 Chiron Corporation 9.9 Diagnostic Products Corporation 9.10 DiagnoSwiss SA 9.11 Digene Corporation 9.12 Genaissance Pharmaceuticals Inc 9.13 Gen-Probe Inc 9.14 HandyLab 9.15 Innogenetics NV 9.16 Interleukin Genetics 9.17 Matritech Inc 9.18 Meridian Bioscience Inc 9.19 Myriad Genetics Inc 9.20 Nanogen 9.21 Nymox Pharmaceutical 9.22 Ostex International 9.23 Qiagen 9.24 Quest Diagnostics Inc 9.25 Quidel Corporation 9.26 Roche Holding Ltd 9.27 SomaLogic 9.28 Tibotec-Virco NV 9.29 Variagenics 9.30 Visible Genetics Inc 9.31 Vysis Inc CHAPTER 10 TRENDS AND OPPORTUNITIES 10.1 Molecular diagnostics in the post-genomic era 10.2 Enhancing the position of immunoassays 10.3 NAT and personalized medicine 10.4 NAT and preventative medicine 10.5 Companion therapeutic/diagnostic approach 10.6 Medical acceptance of molecular diagnostics 10.7 Tests move into POC settings 10.8 High-margin, premium-priced products 10.9 Molecular diagnostics and healthcare costs 10.10 The future is microchip-shaped EXECUTIVE SUMMARY Traditionally, diseases have been classified based on physiological symptoms and diagnostic methods often detected substances only indirectly correlated with a particular disease. As our understanding of the molecular basis of diseases increases, so does our ability to select the most appropriate molecular markers of different diseases. Both proteins and nucleic acids may be specific markers of disease and have diagnostic utility. Based on deeper understanding, molecular diagnostics are being designed to enable early diagnosis of disease, prediction of individual drug responses (theranostic tests), and determination of genetic susceptibility to disease (predisposition tests). Molecular diagnostics are transforming the pharmaceuticals market. Earlier diagnosis permits earlier prescription of appropriate medications and may offer a broader range of therapeutic options; information about individual drug responses enables choice of the most effective drugs for the indiviual patient and avoidance of drugs likely to cause toxic side effects; information about disease predisposition may enable preventative drug treatment. In addition, new drugs are increasing being developed in conjunction with a diagnostic based on the same molecular target. Companies that develop novel gene- or protein-based molecular diagnostics may obtain intellectual property protection and, therefore, may generate higher margins than has traditionally been the case in the diagnostics industry. Molecular diagnostics that are showing strong growth use two technology platforms - immunoassay and nucleic acid testing (NAT). The report reviews developments in both immunoassay technology and NAT technology which are leading to the development of improved molecular diagnostics. Technologically advanced rapid assay formats are driving a point-of-care (POC) market in immunoassays. In the post-genomic era, the potential for new protein biomarker discovery is enormous. Developments in amplification techniques, genotyping methods, DNA microarrays and microfluidics are revolutionizing NAT- based diagnostic testing. A number of efforts are currently underway to discover numerous associations between single nucleotide polymorphisms (SNPs) and diseases. This report focuses on high growth potential immunoassays (principally tumour markers, together with specialty tests such as cardiac, bone, and neurological markers) and nucleic acid tests. The market for such tests was estimated to be worth $2.1 billion worlwide in 2001 (37% of which were NAT tests). This market is forecast to grow at a compound annual growth rate of 16%, to $5 billion worldwide by 2007, of which 50% by value will be NAT tests. This growth rate greatly exceeds that of the IVD market as a whole, which is subject to severe cost containment pressures in most national markets, and is unlikely to increase by more than 4-5% per year. Our forecast annual growth rates for the leading application groups are: tumour markers 8%, speciality immunoassay markers 15%, NAT for infectious disease 21% (except genotyping applications, where we forecast 44%), cancer screening (NAT) 34%, genetic testing 10%, and predispositional/theranostic testing (NAT) 26%. The leading application by sales volume is (and is expected to remain) NAT- based infectious disease testing. The markets for these tests overall will grow slowly in Japan, somewhat faster in the US, and relatively rapidly in Europe (with the exception of Italy). By the end of the forecast period, both the US and Europe will each have around 35% of the worldwide IVD market. Faster growth rates and therefore superior commercial opportunities are expected in Latin America and a few other developing regions. The major suppliers of established immunoassay systems have proved able to leverage their experience in dealing with clinical laboratories in order also to become leading suppliers of NAT products. Such companies include Roche, Abbott, and Bayer, which have at least 30% of the market between them. Molecular diagnostics have already made an impact on the diagnosis and management of communicable diseases, cardiovascular disease and cancer. This report surveys recent developments in each of these therapy areas with an emphasis on commercial products recently launched and those under development. Infectious diseases are the leading cause of death worldwide and take third place in the US. A particular area in which rapid immunoassays are currently making an impact is parasitology, where traditional diagnosis requires microscopy expertise. Early and sensitive detection of viruses and bacteria is currently achieved by means of nucleic acid testing using amplification technologies. Viral load testing has become standard for management of HIV, hepatitis C virus (HCV), and human cytomegalovirus infections, while nucleic acid probe-based testing for HIV and HCV is now in general use for the entire US blood supply. There is a growing clinical acceptance that genotyping to detect emerging drug resistance is vital in guiding the treatment of viral infections. Coronary artery disease (CAD) remains the number one killer in the western world, causing 50% of all death, and is also responsible for 15%-20% of all deaths in developing countries. The market for rapid cardiac immunoassays is particularly dynamic with many new products entering the market. This report reviews emerging protein biomarkers for cardiovascular risk assessment tests and those for early detection of myocardial infarction and congestive heart failure. Predisposition tests on the market and under commercial development detect genetic polymorphisms indicating increased risk for conditions associated with cardiovascular diseases, in particular hypertension or chronic inflammation. Pharmacogenomic tests are becoming available which predict an individual's response to marketed statins or ACE inhibitors. Cancer is the second most common cause of pathological death in developed coutries after cardiovascular disease and is a growing market due to the ageing population. Currently, cancer IVDmarket consists predominantly of immunoassay-based methods which detect tumor markers only indirectly correlated with the cancer. Newer tests have better specificities. Theranostic tests based on protein biomarkers already exist and allow selection of cancer patients for treatment with the drug Herceptin. A number of companies are developing tests which aim to detect genomic abnormalities associated with early-stage cancer. Predisposition tests based on sequencing are available for the major hereditary forms of cancer. Pharmacogenomic tests which will allow tailoring chemotherapeutic therapy to the genetic characteristics of an individual patient and his or her tumor have began to appear on the market. Post-genomic technologies are also enabling researchers to discover molecular signatures of different cancers which may enable earliest possible pre-symptomatic diagnosis. Rapid POC immunoassays based on specific, often novel biomarkers are increasingly employed in prenatal diagnosis, and in the detection and management of a variety of medical conditions and illnesses. Nucleic acid testing already plays an important role in prenatal and pre-implantation diagnosis, identity testing and other conditions. Genetic susceptibility tests for conditions such as periodontal disease, osteoporosis, and diabetes have been developed. Theranostic tests are also becoming available for the prediction of susceptibility to adverse drug reactions, and prediction of responses to drugs used in the treatment of Alzheimer's disease, asthma, rheumatoid arthritis, and schizophrenia. Molecular diagnostics are expected to play an important role in bioterrorism preparedness. Rapid tests to determine the presence of anthrax and other biological warfare agents in the environment already exist, and more sensitive tests are in development. Molecular diagnostics are also being developed for the rapid detection of anthrax in clinical samples.

Publisher:

D&MD Publications Inc

Year of publication:

2002

Type of publication:

Management report

Publisher's reference (if any):

D&MD9081

Author(s):

Sreten Bogdanovic and Beata Langlands

Approximate page count:

280

Price when published:

$4,950

Remarks:

Page numbers, where given, refer to the draft manuscript (which may differ from the published version).
The copyright in this report is owned by the publisher, to whom any requests for copies should be addressed.
The price shown is for a single copy of the print version. Multiple copies and electronic copies usually have different prices.

                              MOLECULAR DIAGNOSTICS:
                     TRANSFORMING THE PHARMACEUTICALS MARKET

                               TABLE OF CONTENTS

         EXECUTIVE SUMMARY

         CHAPTER 1  INTRODUCTION

         1.1 Overview of the IVD industry
            1.1.1 IVD technology segments
            1.1.2 Customers for IVD products
              1.1.2.1 Clinical laboratory market
              1.1.2.2 Point-of-care market
              1.1.2.3 Over-the-counter market

         1.2 Traditional in vitro diagnostics

         1.3 Molecular diagnostics

         1.4 Platform technologies for molecular diagnostics
            1.4.1 Rapid immunoassays
            1.4.2 Nucleic acid testing (NAT)
            1.4.3 Biochips

         1.5 Uses of traditional IVDs in clinical settings
            1.5.1 Unique uses of molecular diagnostics

         1.6 Diagnostic kits and homebrew tests

         Chapter 2  Technology developments

         2.1 Immunoassay technology
            2.1.1 Introduction
            2.1.2 Principles and terms
            2.1.3 Standardization
            2.1.4 Immunoassay design
              2.1.4.1 Competitive assays
              2.1.4.2 Noncompetitive "sandwich" assays
            2.1.5 Point-of-care immunoassays
              2.1.5.1 Chromatographic lateral flow devices
            2.1.6 Protein chips
              2.1.6.1 Miniaturization of immunoassays

         2.2 Nucleic acid testing technology
            2.2.1 Introduction
            2.2.2 Principles and terms
            2.2.3 DNA probes and their uses
            2.2.4 Nucleic acid amplification techniques
              2.2.4.1 Target amplification
              2.2.4.2 Signal amplification
            2.2.5 DNA chips and miniaturization
              2.2.5.1 DNA microarrays
              2.2.5.2 Microfluidic devices
            2.2.6 Genotyping methods
              2.2.6.1 Use of DNA sequencers
              2.2.6.2 Use of microarrays
            2.2.7 Evolution of rapid point-of-care formats

         CHAPTER 3  MOLECULAR DIAGNOSTICS FOR COMMUNICABLE DISEASES

         3.1 Introduction

         3.2 Immunodiagnostic tests
            3.2.1 Introduction
            3.2.2 Rapid immunoassays

         3.3 Nucleic acid tests
            3.3.1 Introduction
            3.3.2 Tests for viruses
              3.3.2.1 HIV viral load and drug resistance
              2.3.2.2 HBV/HCV viral load and drug resistance
              3.3.2.3 CMV
              3.3.2.4 HPV
              3.3.2.5 Other viruses
            3.3.3 Blood testing for viruses
            3.3.4 Tests for bacteria
              3.3.4.1 Chlamydia and gonorrhea
              3.3.4.2 Mycobacteria
              3.3.4.3 Other bacteria
              3.3.4.4 Detection of antibiotic resistance
            3.3.5 Tests for fungi and parasites

         CHAPTER 4  MOLECULAR DIAGNOSTICS FOR CARDIOLOGY

         4.1 Introduction
            4.1.1 Coronary Artery Disease
              4.1.1.1 Risk factors
            4.1.2 Myocardial infarction (MI)
              4.1.2.1 Diagnosis
            4.1.3 Congestive Heart Failure (CHF).
              4.1.3.1 Diagnosis

         4.2 Immunodiagnostic tests
            4.2.1 Cardiovascular risk assessment tests
              4.2.1.1 Homocysteine
              4.2.1.2 C-Reactive Protein
              4.2.1.3 Autoantibodies to oxidised LDL
              4.2.1.4 Apolipoprotein B
              4.2.1.5 Lipoprotein-associated phospholipase A2
              4.2.1.6 Other biomarkers of potential value
            4.2.2 Early detection of MI
              4.2.2.1 The cardiac troponins T and I
              4.2.2.2 Other cardiac markers
            4.2.3 Early diagnosis of CHF
              4.2.3.1 B-type natriuretic peptide

         4.3 NAT-based tests
            4.3.1 Genes and cardiovascular disease
            4.3.2 Predictive tests on the market
            4.3.3 Predictive tests under commercial development

         CHAPTER 5  MOLECULAR DIAGNOSTICS FOR ONCOLOGY

         5.1 Introduction
            5.1.1 Overview of cancer
              5.1.1.1 Importance of early detection
            5.1.2 Diagnosis

         5.2 Immunodiagnostic tests
            5.2.1 Introduction to tumor markers
            5.2.2 Leading circulating tumor markers
              5.2.2.1 PSA and cPSA
              5.2.2.2 CA 125, CA 15-3, CA 19-9
              5.2.2.3 CEA
              5.2.2.4 AFP, HCG
              5.2.2.5 VEGF
            5.2.3 Novel circulating biomarkers
              5.2.3.1 Kallikreins
              5.2.3.2 Cancer-specific antibodies
            5.2.4 Leading urine biomarkers
              5.2.4.1 BTA stat test
              5.2.4.2 NMP22 test
              5.2.4.3 Accu-Dx test
              5.2.4.4 Other potential urine biomarkers
            5.2.5 New biomarker discovery
            5.2.6 Theranostic tests

         5.3 Nucleic acid tests
            5.3.1 FISH-based tests
            5.3.2 Predisposition tests based on sequencing
              5.3.2.1 Hereditary breast cancer
              5.3.2.2 Hereditary colorectal cancer
              5.3.2.3 Hereditary kidney cancer
            5.3.3 Detection of early-stage cancer
              5.3.3.1 DNA in tumor cells
              5.3.3.2 Circulating tumor nucleic acids
              5.3.3.3 Tumor DNA in stool
              5.3.3.4 Tumor DNA in urine
            5.3.4 Detection of specific tumor markers
            5.3.5 Theranostic tests

         5.4 The promise of molecular signatures

         CHAPTER 6  MOLECULAR DIAGNOSTICS FOR MISCELLANEOUS CONDITIONS

         6.1 Immunodiagnostic tests
            6.1.1 Prenatal diagnosis
            6.1.2 Drugs of abuse
            6.1.3 Alzheimer's disease
            6.1.4 Diabetes mellitus
            6.1.5 Bone turnover
            6.1.6 Assessment of oxidative stress

         6.2 NAT-based assays
            6.2.1 Overview
            6.2.2 Screening for common monogenic diseases
              6.2.2.1 Hemochromatosis
              6.2.2.2 Cystic fibrosis
            6.2.3 Prenatal and pre-implantation diagnosis
              6.2.3.1 FISH-based tests on fetal cells
              6.2.3.2 Fetal DNA testing
            6.2.4 Other applications of DNA diagnostics
              6.2.4.1 Alzheimer's disease
              6.2.4.2 Organ transplantation
              6.2.4.3 Identity testing
              6.2.4.4 Posttrauma monitoring
            6.2.5 Genetic susceptibility tests
              6.2.5.1 Risk for periodontal disease
              6.2.5.2 Risk for osteoporosis
              6.2.5.3 Risk for complications from diabetes
              6.2.5.4 Type 1 diabetes
            6.2.6 Theranostic tests
              6.2.6.1 Prediction of drug toxicity
              6.2.6.2 Cholinomimetics (Alzheimer's disease)
              6.2.6.3 Albuterol (asthma)
              6.2.6.4 Rheumatoid arthritis therapy
              6.2.6.5 Clozapine (schizophrenia)

         CHAPTER 7  BIOTERRORISM AND MOLECULAR DIAGNOSTICS

         7.1 Introduction
            7.1.1 Biological warfare agents (BWAs)
            7.1.2 US government initiatives
            7.1.3 IVD industry and bioterrorism preparedness

         7.2 Anthrax and other BWAs in the environment
            7.2.1 Rapid lateral flow immunoassays
            7.2.2 Biosensors
              7.2.2.1 Immunosensors
              7.2.2.2 Synthetic receptor-based sensors
              7.2.2.3 DNA sensors
              7.2.2.4 Reagentless sensors

         7.3 Anthrax in clinical samples
            7.3.1 Traditional laboratory diagnosis
            7.3.2 Rapid diagnostic tests
              7.2.3.1 PCR-based laboratory tests
              7.2.3.2 Rapid immunoassays

         7.4 Developments in biochips

         CHAPTER 8  MARKET CONSIDERATIONS AND FORECASTS

         8.1 Overview of the major world IVD markets
            8.1.1 Global population growth
            8.1.2 The US market
              8.1.2.1 Health and healthcare
              8.1.2.2 The market for IVD products
              8.1.2.3 Regulation of IVD products
            8.1.3 The Japanese market
              8.1.3.1 Health and healthcare
              8.1.3.2 The market for IVD products
              8.1.3.3 Regulation of IVD products
            8.1.4 The European market
              8.1.4.1 EC-wide regulation of IVD products
            8.1.5 Germany
              8.1.5.1 Health and healthcare
              8.1.5.2 The market for IVD products
            8.1.6 Italy
              8.1.6.1 Health and healthcare
              8.1.6.2 The market for IVD products
            8.1.7 France
              8.1.7.1 Health and healthcare
              8.1.7.2 The market for IVD products
            8.1.8 Spain
              8.1.8.1 Health and healthcare
              8.1.8.2 The market for IVD products
            8.1.9 United Kingdom
              8.1.9.1 Health and healthcare
              8.1.9.2 The market for IVD products
            8.1.10 Emerging IVD markets

         8.2 Market forecasts
            8.2.1 IVD sales and forecasts by country
            8.2.2 Oulook for the total immunoassay market
            8.2.3 Outlook for the total NAT market
            8.2.4 Forecasts for molecular diagnostics
              8.2.4.1 Forecasts by application
              8.2.4.2 Forecasts by geographical region

         CHAPTER 9  COMPANY PROFILES

         9.0 Introduction

         9.1 Abbott Laboratories Inc

         9.2 AmpliStar

         9.3 Bayer AG

         9.4 Biopixel Ltd

         9.5 Biosite Diagnostics Inc

         9.6 Cepheid

         9.7 Chembio Diagnostic Systems Inc

         9.8 Chiron Corporation

         9.9 Diagnostic Products Corporation

         9.10 DiagnoSwiss SA

         9.11 Digene Corporation

         9.12 Genaissance Pharmaceuticals Inc

         9.13 Gen-Probe Inc

         9.14 HandyLab

         9.15 Innogenetics NV

         9.16 Interleukin Genetics

         9.17 Matritech Inc

         9.18 Meridian Bioscience Inc

         9.19 Myriad Genetics Inc

         9.20 Nanogen

         9.21 Nymox Pharmaceutical

         9.22 Ostex International

         9.23 Qiagen

         9.24 Quest Diagnostics Inc

         9.25 Quidel Corporation

         9.26 Roche Holding Ltd

         9.27 SomaLogic

         9.28 Tibotec-Virco NV

         9.29 Variagenics

         9.30 Visible Genetics Inc

         9.31 Vysis Inc

         CHAPTER 10  TRENDS AND OPPORTUNITIES

         10.1 Molecular diagnostics in the post-genomic era

         10.2 Enhancing the position of immunoassays

         10.3 NAT and personalized medicine

         10.4 NAT and preventative medicine

         10.5 Companion therapeutic/diagnostic approach

         10.6 Medical acceptance of molecular diagnostics

         10.7 Tests move into POC settings

         10.8 High-margin, premium-priced products

         10.9 Molecular diagnostics and healthcare costs

         10.10 The future is microchip-shaped

EXECUTIVE SUMMARY
Traditionally, diseases have been classified based on physiological symptoms and diagnostic methods often detected substances only indirectly correlated with a particular disease. As our understanding of the molecular basis of diseases increases, so does our ability to select the most appropriate molecular markers of different diseases. Both proteins and nucleic acids may be specific markers of disease and have diagnostic utility.
Based on deeper understanding, molecular diagnostics are being designed to enable early diagnosis of disease, prediction of individual drug responses (theranostic tests), and determination of genetic susceptibility to disease (predisposition tests).
Molecular diagnostics are transforming the pharmaceuticals market. Earlier diagnosis permits earlier prescription of appropriate medications and may offer a broader range of therapeutic options; information about individual drug responses enables choice of the most effective drugs for the indiviual patient and avoidance of drugs likely to cause toxic side effects; information about disease predisposition may enable preventative drug treatment. In addition, new drugs are increasing being developed in conjunction with a diagnostic based on the same molecular target. Companies that develop novel gene- or protein-based molecular diagnostics may obtain intellectual property protection and, therefore, may generate higher margins than has traditionally been the case in the diagnostics industry.
Molecular diagnostics that are showing strong growth use two technology platforms - immunoassay and nucleic acid testing (NAT). The report reviews developments in both immunoassay technology and NAT technology which are leading to the development of improved molecular diagnostics. Technologically advanced rapid assay formats are driving a point-of-care (POC) market in immunoassays. In the post-genomic era, the potential for new protein biomarker discovery is enormous. Developments in amplification techniques, genotyping methods, DNA microarrays and microfluidics are revolutionizing NAT- based diagnostic testing. A number of efforts are currently underway to discover numerous associations between single nucleotide polymorphisms (SNPs) and diseases.
This report focuses on high growth potential immunoassays (principally tumour markers, together with specialty tests such as cardiac, bone, and neurological markers) and nucleic acid tests. The market for such tests was estimated to be worth $2.1 billion worlwide in 2001 (37% of which were NAT tests). This market is forecast to grow at a compound annual growth rate of 16%, to $5 billion worldwide by 2007, of which 50% by value will be NAT tests. This growth rate greatly exceeds that of the IVD market as a whole, which is subject to severe cost containment pressures in most national markets, and is unlikely to increase by more than 4-5% per year.
Our forecast annual growth rates for the leading application groups are: tumour markers 8%, speciality immunoassay markers 15%, NAT for infectious disease 21% (except genotyping applications, where we forecast 44%), cancer screening (NAT) 34%, genetic testing 10%, and predispositional/theranostic testing (NAT) 26%. The leading application by sales volume is (and is expected to remain) NAT- based infectious disease testing.
The markets for these tests overall will grow slowly in Japan, somewhat faster in the US, and relatively rapidly in Europe (with the exception of Italy). By the end of the forecast period, both the US and Europe will each have around 35% of the worldwide IVD market. Faster growth rates and therefore superior commercial opportunities are expected in Latin America and a few other developing regions. The major suppliers of established immunoassay systems have proved able to leverage their experience in dealing with clinical laboratories in order also to become leading suppliers of NAT products. Such companies include Roche, Abbott, and Bayer, which have at least 30% of the market between them.
Molecular diagnostics have already made an impact on the diagnosis and management of communicable diseases, cardiovascular disease and cancer. This report surveys recent developments in each of these therapy areas with an emphasis on commercial products recently launched and those under development.
Infectious diseases are the leading cause of death worldwide and take third place in the US. A particular area in which rapid immunoassays are currently making an impact is parasitology, where traditional diagnosis requires microscopy expertise. Early and sensitive detection of viruses and bacteria is currently achieved by means of nucleic acid testing using amplification technologies. Viral load testing has become standard for management of HIV, hepatitis C virus (HCV), and human cytomegalovirus infections, while nucleic acid probe-based testing for HIV and HCV is now in general use for the entire US blood supply. There is a growing clinical acceptance that genotyping to detect emerging drug resistance is vital in guiding the treatment of viral infections.
Coronary artery disease (CAD) remains the number one killer in the western world, causing 50% of all death, and is also responsible for 15%-20% of all deaths in developing countries. The market for rapid cardiac immunoassays is particularly dynamic with many new products entering the market. This report reviews emerging protein biomarkers for cardiovascular risk assessment tests and those for early detection of myocardial infarction and congestive heart failure. Predisposition tests on the market and under commercial development detect genetic polymorphisms indicating increased risk for conditions associated with cardiovascular diseases, in particular hypertension or chronic inflammation. Pharmacogenomic tests are becoming available which predict an individual's response to marketed statins or ACE inhibitors.
Cancer is the second most common cause of pathological death in developed coutries after cardiovascular disease and is a growing market due to the ageing population. Currently, cancer IVDmarket consists predominantly of immunoassay-based methods which detect tumor markers only indirectly correlated with the cancer. Newer tests have better specificities. Theranostic tests based on protein biomarkers already exist and allow selection of cancer patients for treatment with the drug Herceptin. A number of companies are developing tests which aim to detect genomic abnormalities associated with early-stage cancer. Predisposition tests based on sequencing are available for the major hereditary forms of cancer. Pharmacogenomic tests which will allow tailoring chemotherapeutic therapy to the genetic characteristics of an individual patient and his or her tumor have began to appear on the market. Post-genomic technologies are also enabling researchers to discover molecular signatures of different cancers which may enable earliest possible pre-symptomatic diagnosis.
Rapid POC immunoassays based on specific, often novel biomarkers are increasingly employed in prenatal diagnosis, and in the detection and management of a variety of medical conditions and illnesses. Nucleic acid testing already plays an important role in prenatal and pre-implantation diagnosis, identity testing and other conditions. Genetic susceptibility tests for conditions such as periodontal disease, osteoporosis, and diabetes have been developed. Theranostic tests are also becoming available for the prediction of susceptibility to adverse drug reactions, and prediction of responses to drugs used in the treatment of Alzheimer's disease, asthma, rheumatoid arthritis, and schizophrenia.
Molecular diagnostics are expected to play an important role in bioterrorism preparedness. Rapid tests to determine the presence of anthrax and other biological warfare agents in the environment already exist, and more sensitive tests are in development. Molecular diagnostics are also being developed for the rapid detection of anthrax in clinical samples.