Theranostics: The influence of diagnostics on pharmaceutical therapy

Theranostics: The influence of diagnostics on pharmaceutical therapy

The 'theranostic' or 'predictive medicine' has been in existence for some time but it is now that its importance is intensifying.

This forward-thinking report examines how this new genre of diagnostic will affect the pharmaceutical and diagnostic industries. It gives an expert assessment of the pros and cons.

The report examines the role of theranostics in clinical trials, the leading companies and provides an analysis of theranostics by disease area. It examines the products and new technologies in the areas of cancer; infectious diseases; diabetes; osteoporosis; Alzheimer's and arthritis.

This report contains views from leading industry experts.

Companies profiled: Abbott; Affymetrix; Amrad; AstraZeneca; Axis-Shield; Bayer; Becton Dickinson; Bion Diagnostic Sciences; Biosite; Bristol-Myers Squibb; Cholestech; CompuCyte; Dako; Digene; Gemini (Eurona); Genetics Institute; Gen-Probe; Genset; GlaxoWellcome; Hyseq; ImClone; Lexon; Meridian Diagnostics; Micromet; Millennium Predictive Medicine; Myriad Genetics; Orchid Biocomputer; Ostex International; Pharmanetics; Provalis (Cortecs); Quark Biotech; Quidel; Roche; Saliva Diagnostics Systems; Sequenom; Trinity Biotech; Visible Genetics; Vysis.

Price: £750/$1,495/¥180,000
Published: June 2000
Pages: 140+
Ref: CBS845E

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CONTENTS
LIST OF TABLES
LIST OF FIGURES
EXECUTIVE SUMMARY

ES.1 The implications for the pharmaceutical industry
ES.2 The implications for the diagnostics industry

ABBREVIATIONS
SCOPE & METHODOLOGY

1.1 Scope and objectives of the report
1.2 Methodology

CHAPTER 1 INTRODUCTION

CHAPTER 2 WHAT ARE THE IMPLICATIONS OF THERANOSTICS FOR THE DIAGNOSTICS AND PHARMA INDUSTRIES?
2.1 Introduction
2.2 Growth slows in traditional in vitro diagnostic markets
2.3 Which technologies are good investments?
2.4 The current structure of the industry
2.4.1 The diagnostics industry
2.4.2 The pharmaceutical industry
2.4.3 Nucleic acid testing
2.4.4 Point-of-care testing
2.5 Three key areas for theranostic use
2.5.1 Preventative and predisposition testing
2.5.1.1 Genetic testing issues
2.5.2 Diagnosing disease and therapy selection
2.5.2.1 Criteria for clinical use of a diagnostic to predict drug response
2.5.3 Therapy monitoring
2.6 Implications for the pharma industry
2.7 Implications for the diagnostics industry
2.8 Why hasn't the theranostics sector taken off sooner?
2.9 A further wave of merger and acquisition activity?
2.10 Drivers and enablers for theranostics
2.10.1 Some pitfalls to promotion via the Internet
2.11 Traditional diagnostics or pharmacogenetics?
2.12 Theranostic case studies
2.12.1 Glaxo Wellcome
2.12.2 Roche
2.12.3 Influenza
2.12.4 Unmet opportunities for theranostics
2.12.4.1 Irritable bowel syndrome
2.12.4.2 Migraine
2.13 Regional differences

CHAPTER 3 WHICH DIAGNOSTIC TECHNOLOGIES ARE LIKELY TO INFLUENCE THERAPY?
3.1 Introduction
3.2 Point-of-care testing
3.2.1 Miniature spectrophotometry
3.2.2 Lateral flow immunoassays
3.2.3 Immunochromatographic technology
3.2.4 Colorimetric assays
3.2.5 Cardiac markers
3.2.6 Coagulation testing
3.2.7 Rapid bladder cancer test
3.2.8 HIV
3.2.9 Influenza
3.2.10 Lipid profiling
3.2.11 Osteoporosis
3.2.12 The need for point-of-care connectivity and information collection systems
3.3 Nucleic acid testing
3.3.1 Infectious disease testing
3.3.1.1 Direct probe techniques
3.3.1.2 Target amplification techniques
3.3.2 Single nucleotide polymorphism testing
3.3.2.1 Target amplification techniques
3.3.2.2 Mutation discrimination techniques
3.3.2.3 Signalling techniques
3.3.3 Fluorescence in situ hybridisation
3.3.4 Which technology will be the winner?
3.3.5 Other theranostic examples
3.3.5.1 HercepTest
3.3.5.2 Eurona's ACE inhibitor test

CHAPTER 4 WHICH COMPANIES ARE ACTIVE IN THIS AREA?
4.1 Introduction
4.2 Abbott
4.3 Affymetrix
4.4 Amrad
4.5 AstraZeneca
4.6 Axis-Shield
4.7 Bayer
4.8 Becton Dickinson
4.9 Bion Diagnostic Sciences
4.10 Biosite
4.11 Bristol-Myers Squibb
4.12 Cholestech
4.13 CompuCyte and Genetics Institute
4.14 Cytocell
4.15 Dako
4.16 Digene
4.17 Eurona/Gemini Holdings
4.18 Gen-Probe
4.19 Genset
4.20 Glaxo Wellcome
4.21 Hyseq
4.22 ImClone
4.23 Lexon
4.24 Meridian
4.25 Metrika
4.26 Micromet
4.27 Millennium Predictive Medicine
4.28 Myriad Genetics
4.29 Orchid Biocomputer
4.30 Ostex International
4.31 PharmaNetics
4.32 Provalis (Cortecs)
4.33 Quark Biotech
4.34 Quidel
4.35 Roche
4.35.1 Sales growth at above industry average
4.35.2 Roche's integrated approach to healthcare
4.35.3 Patent and litigation problems
4.36 Saliva Diagnostics
4.37 Sequenom
4.38 Trinity Biotech
4.39 Visible Genetics
4.40 Vysis

CHAPTER 5 THE ROLE OF THERANOSTICS IN CLINICAL TRIALS
5.1 Introduction
5.2 The use of screening tests for clinical trials
5.3 The use of diagnostic tests during clinical trials
5.4 The use of diagnostic tests to determine end points
5.5 The FDA's view of markers in clinical trials
5.5.1 Osteoporosis
5.5.1.1 Hormone replacement therapy
5.5.1.2 Bisphosphonates
5.5.1.3 Selective oestrogen receptor modulators
5.5.1.4 Calcitonin
5.5.2 Arthritis
5.5.2.1 Rheumatoid arthritis
5.5.2.2 Osteoarthritis
5.5.3 HIV
5.6 Selecting the most appropriate pharmacogenetic information

CHAPTER 6 ANALYSIS OF THERANOSTICS BY DISEASE AREA
6.1 Cardiovascular disease
6.1.1 Cardiac markers
6.1.2 Coagulation tests
6.1.2.1 Stroke
6.1.3 Pharmacogenetic tests
6.2 Diabetes
6.3 Cancer
6.3.1 Herceptin/HercepTest
6.3.1.1 Herceptin's potential in other tumours
6.3.2 Other theranostics for breast cancer
6.3.3 Lung cancer
6.3.4 Ovarian cancer
6.3.5 Colon cancer
6.3.6 Bladder cancer
6.3.7 General tests for cancer
6.4 Infectious diseases
6.4.1 HIV
6.4.1.1 Viral genotyping
6.4.1.2 Evaluation of drug resistance
6.4.1.3 More sensitive tests
6.4.1.4 The potential for home monitoring
6.4.1.5 Other new tests
6.4.2 Helicobacter pylori
6.4.3 Influenza
6.4.4 Hepatitis
6.4.5 Herpes
6.4.6 Antimicrobial resistance
6.4.7 Others
6.5 Osteoporosis
6.6 Alzheimer's disease
6.6.1 Determining responders
6.6.2 Reimbursement issues
6.6.3 Diagnosis
6.7 Arthritis
REFERENCES

LIST OF TABLES
Table 2.1 Key players in the diagnostics industry - the top 8
Table 2.2 Key players in the pharmaceutical industry - the top 10
Table 2.3 Nucleic acid diagnostic techniques
Table 2.4 Companies with nucleic acid diagnostics
Table 2.5 Key requirements for a diagnostic
Table 2.6 Selected companies with POC tests
Table 2.7 POC testing market by product segment, 1997
Table 2.8 Drivers and enablers for theranostics
Table 3.1 Selection of companies with POC tests
Table 3.2 Leading companies with nucleic acid diagnostic techniques
Table 3.3 Commercially available amplified infectious disease tests
Table 4.1 Millennium Pharmaceuticals' partnerships
Table 6.1 Relapse rates in patients with ovarian cancer

LIST OF FIGURES
Figure 2.1 Diagnosis and treatment in the 20th century
Figure 2.2 A model for the 21st century
Figure 2.3 Integration of a genomic drug and a diagnostic
Figure 3.1 PharmaNetics' Thrombolytic Assessment System
Figure 5.1 Required qualities of a diagnostic test for clinical trials

EXECUTIVE SUMMARY
The term 'theranostics' describes an evolving group of products that link diagnostics with pharmaceutical treatment. They are also known by some companies as 'predictive medicine'. The theranostic might identify which patients would be most suited to a particular drug therapy or could be used to provide feedback on how well a drug is working in order to tailor the optimum treatment regimen. Many theranostics need to be point-of-care (POC) tests. In many cases, the results of the tests need to be available quickly and at the patient's side, in order to influence therapy.

The pharmaceutical industry is investing heavily in pharmacogenomics research and this will undoubtedly result in many more new tests. These tests will have an influence to bear on therapeutic decisions, giving physicians more information on which therapy will be most beneficial to a patient and then allowing them to monitor the patient's progress.

Historically, there has been mistrust and misunderstanding between the pharmaceutical and the diagnostic industries. With the advent of the evolving theranostics sector, there is now a greater need for dialogue and for the two industries to work together.

The objective of this report is to highlight the areas where theranostics are having the greatest influence. It highlights both the positive and negative implications for the diagnostics and pharma industries. It also provides a review of the current technology available in this area and discusses the major market players and their strategies.

Although theranostic-style tests have been around for decades, a well known example of a theranostic is Dako's HercepTest, which is used to select patients with breast cancer who would benefit from the Genentech drug, Herceptin. It was the US approval of HercepTest which marked the beginning of the theranostic era. Of crucial importance was the FDA's decision that Herceptin could only be administered to patients who had been identified by the HercepTest as suitable candidates for treatment. This was the first time that the agency had required a particular test be performed before a drug can be used.

The world in vitro diagnostics market is worth $19 billion and is currently growing at a rate of 3-5% per annum. This rate of growth has slowed from 10% per annum 10 years ago and for traditional diagnostic products will slow still further to around 1-2% per annum. Some areas such as nucleic acid probes, POC testing and glucose monitoring, show strong growth, but together these account for less than 20% of the market. Companies in the diagnostics industry will have to put their efforts into the growth areas if they are to continue to succeed.

Technology in the field of theranostics essentially falls into two categories. The first is the development of traditional diagnostics into POC assays, which can be used in the doctor's office, at the patient's bedside or for self-testing. This sector has long been heralded as the new direction for the diagnostics industry. However, its take-up has been slower than predicted for a number of reasons, as discussed later. The second is the burgeoning use of nucleic acid testing (NAT) for infectious diseases or to determine a patient's susceptibility to disease and therapy response from their genetic make-up.

Over the next five years, theranostics will start to have a major impact on the diagnostics market. NAT will begin to be used in patient stratification - selecting the patients who are most likely to respond to a certain treatment.

NAT is the highest growth sector in the diagnostics industry. In the nucleic acid diagnostics sector, Roche is the major player with its PCR technology (Amplicor). There are also a number of other techniques developed, such as Bayer's bDNA. These have found a key role, for example in monitoring HIV viral levels in conjunction with anti-viral therapy.

However, many of the techniques used in NAT are often complicated, requiring skilled handling that can only be done in a laboratory with specialised equipment. The industry is just beginning to turn research products into commercially available realities.

At present the largest sector for NAT is in infectious diseases. A small but evolving sector is in predisposition testing, but development is being restricted until definitive links have been shown between genes and therapy. The third important area for NAT is for cancer genes. The technology here is still in its infancy.

The use of theranostic technologies can be divided into three key areas. These are:

Preventative and predisposition testing
Diagnosing disease and therapy selection
Therapy monitoring

ES.1 The implications for the pharmaceutical industry
A theranostic link up can offer distinct strategic advantages over competitors. A potent and expensive drug supported by a rapid, easy-to-use theranostic is more cost-effective than a similar drug without such support. This is likely to be welcomed by doctors who are increasingly under pressure to justify their choice of treatment. For drugs already on the market, the theranostic could provide medical and economic data to support their use.

An important area in which theranostics can play a key role is in clinical trials for new therapies. Theranostics can be used for selecting the patient population for the trial, and for monitoring the effects of the therapy during the study. This information can be used as evidence of efficacy in regulatory applications and can potentially shorten the duration and reduce the cost of clinical trials.

While there has been a great deal of resistance and suspicion among pharmaceutical companies about the use of tests that could effectively rule out the use of their drugs in certain patients, there are encouraging trends developing in the combined use of drugs and diagnostics.

The evolution of this new area will mean that pharmaceutical companies will move away from traditional drug development processes to the use of targeted research using pharmacogenomics and molecular diagnostics to produce tailored therapies.

ES.2 The implications for the diagnostics industry Some in the diagnostics industry believe that there will come a time when diagnostic companies will no longer be selling to their traditional customers, the analytical laboratories, or even to doctors and other medical staff. They foresee a situation where their main customers will be the pharmaceutical companies, clinical research organisations and even the patients themselves. But will this mean that powerful and better-financed drugs companies offer diagnostics free with their therapeutics? The jury still seems to be out and companies such as Glaxo Wellcome say that they will make decisions on a case-by-case basis, depending on the market situation.

In the diagnostics industry the sales forces are generally small. The reps concentrate on visiting hospitals, particularly laboratories, and in general, they do not visit primary care physicians, because there are not enough of them. However, the big pharmaceutical companies have reps that are visiting all of the GPs and for them to give information on a test in a particular therapeutic area could be very beneficial for the diagnostic company. So there are great opportunities for co-marketing collaborations.

An alternative view, voiced by some in the industry, is that the availability of theranostic tests could radically change market share for some products. The application of all this technology could shift the current flow of healthcare dollars from the less than 1% currently spent on diagnostics to 5% or more of the total. The idea is that the impact on patient care and the economics of that care will force a shift of expenditure from drugs to diagnostics.

One day, it seems that most, if not all, medicines will be prescribed using a diagnostic patient profile, which will require links between pharmaceutical and diagnostic companies. It is still unclear as to how this will effect existing diagnostic companies, but there is little doubt that the effect will change the industry.

Who is interested in theranostics? One of the biggest influences on the theranostics market will be the drive by payers to reduce healthcare costs. This includes governments, insurance companies, the National Institute of Clinical Excellence (NICE) and EuroNICE. The regulators are interested because they want to see prevention of adverse events. Patients are increasingly interested in the choice of their therapy and shareholders will be interested as it opens up new business areas. Areas in which there has been most work on theranostic development include infectious diseases, diabetes, cardiac markers, coagulation testing, cancer, Alzheimer's, arthritis and osteoporosis.

The leading companies in the field of theranostics include Abbott, Affymetrix, AstraZeneca, Bayer, Dako, Digene, Gemini (Eurona), Gen-Probe, Glaxo Wellcome, Hyseq, Millennium Predictive Medicine, Myriad Genetics, PharmaNetics, Provalis, Quidel, Roche and Sequenom.