Transcript Bio Pharm 98 Speaker slide template

The Horizons of Predictive
Medicine
Dr Ian Gilham
Worldwide Director, Predictive Medicine
Glaxo Wellcome Research and
Development
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What is a diagnostic?
“A device or service that provides specific
information on the current health status of
an individual”
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However………...
Newer technologies can be used to
determine
 Predisposition to future change in health
status
 Monitoring of health status
 Suitability for specific medicines
A better description would be…...
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Predictive Medicine
“A device or service that can predict a
change in the health status of an
individual, either towards the onset of
disease or towards the likely response to
a therapeutic intervention.”
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What is Predictive
Medicine?
Diagnostics
Surrogates
Prognostics
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20th Century
SYMPTOMS OF DISEASE
DIAGNOSTICS
(IVD, IMAGING)
THERAPEUTIC
INTERVENTION
OUTCOME
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21st Century
PREDISPOSITION PROFILING
(GENETICS, FUNCTIONAL GENOMICS)
MONITORING AND PREVENTION
(BEHAVIOUR MODIFICATION, SURROGATES, VACCINES ETC)
DIAGNOSTICS
(IVD, IMAGING)
TREATMENT SELECTION
(PHARMACOGENETICS)
THERAPEUTIC
INTERVENTION
TREATMENT MONITORING
(THERAPEUTIC RESPONSE, SURROGATES, COMPLIANCE)
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PREDICTIVE
MEDICINE
Right Medicine
Right Patient
INNOVATIVE
MEDICINES
Right Disease
Right Time
Right Dose
PATIENT-TARGETED
THERAPIES
Right Response
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The drivers and enablers of
Predictive Medicine
Diagnosis
-- Tomorrow --
Drivers
-- Today --
Enablers
Treatment
• Payer pressures (governments/insurance firms):
more prevention, more effective cures
• Regulator pressure to try to eliminate adverse events
• Demand for better healthcare from the patient
• Demand for more accurate healthcare predictions for
the patient
• Shareholder expectation of growth - getting better
medicines to the market faster
Prediction
Prevention
• Development of Genetics and Functional Genomics
knowledge
• New technologies (e.g. genechips, bioinformatics,
molecular diagnostics, etc.)
• New regulation on Intellectual Property Rights,
genomic ethics, data protection & consent
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Potential areas of interest
Genetics
Diagnostics
Molecular
Diagnostics
Gene Therapy
Predisposition
Profiling
Population
Stratification
Vaccines
In Vitro
Diagnostics
Health
Outcomes
Monitoring
Devices
Non-Therapeutic
Intervention
Therapeutic
Intervention
Proteins
Compliance
Small
Molecules
Therapeutics
Imaging
Pharmacoeconomics
Disease
Management
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Application of Predictive
Medicine

Disease Detection

Disease Intervention
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Susceptibility Gene Strategy
Alzheimer Disease
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Human Genetics

Over the past two decades, disease genes
have been identified for hundreds of rare,
inherited diseases that are seen in families

Susceptibility genes underlie common
diseases (e.g. diabetes, heart disease,
asthma)

To date, only one susceptibility gene linked
to a common, polygenic disease (APOE,
Alzheimer)
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Glaxo Wellcome Genetics Strategy

To identify susceptibility genes contributing to
the risk and age of onset of common diseases
with high unmet need

Identify the 20-30 most relevant genes for
specific diseases, using genetics and genomic
tools.

Focusing to find specific susceptibility genes is
the art
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Genetics Research Outcomes
Gene Analysis
Development of “mechanism-based”
medicines
Definition of
underlying
Disease
Mechanisms
Gene Expression
Analysis
Right
medicines
to Right
Patient
Disease
Segmentation
Development of Diagnostics
to detect Disease segment
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Changing technology will accelerate
susceptibility gene discovery
Current genomic
screening technology (today)
Database of well
characterised
patients &
their DNA
Genetic
epidemiology
Gene - Disease
associations
Database of genetic
polymorphism and
high capacity resequencing
technology
(in development)
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Alzheimer costs a lot
today…...

2.3 million Alzheimer cases in the US
4% of 75 year olds
 8.5% of 80 year olds
 28.5% of 90 year olds

360,000 new US cases each year
 US costs estimated at $90bn annually

Source: Reuters 1998
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Alzheimer will cost more
tomorrow….
1992 - 7.0% of population over 75 years
old
 2051 - 13.6% of population over 75
years old
 Estimated 7.5m to 14.3m Alzheimer
sufferers in the US by 2050

Source: Prevention of Alzheimer Disease JAMA (262): p251
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APOE in Alzheimer disease a susceptibility Gene
Proportion of each
genotype unaffected
1.0
Mean age of
onset of
Alzheimer
disease as a
function of the
inheritance of the
five common
APOE genotypes
2/3
0.8
0.6
3/3
2/4
0.4
3/4
0.2
0
60
4/4
65
70
75
80
85
90
Age at onset
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Significance of APOE

Predictive Medicine

Drug Discovery
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Symptomatic Alzheimer Diseas
Source: Reiman et al NEJM 334 p752
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APOE4 Homozygotes
Source: Reiman et al NEJM 334 p752
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APOE as a Predictive
Medicine Tool in Alzheimer
Disease


Value in assigning more accurate
diagnoses, not simply whether a patient is
APOE4 “positive” or APOE4 “negative”
If a patient is cognitively impaired, and fits
the current clinical diagnosis of possible AD,
the diagnostic accuracy goes from 60-70%
to >95% if the patient carries an APOE4
allele
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APOE as a potential
diagnostic
Considerations
Rigorous test validation
 Role of APOE in other neurological
conditions
 Value of a diagnostic in the absence of
an effective therapy
 Outcomes analysis
 Regulatory considerations

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Significance of APOE

Predictive Medicine

Drug Discovery
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Disease Mechanism and
Target Identification
Strategy
Create a transgenic animal with the only
difference being the human
polymorphism isoform associated with
disease
 Determing differences in appropriate
organs

Differential Gene Expression
 Proteomics
 Others

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APOE GeneCalling Study
APOE knock out (KO) mouse = normal
 ID “rescue” genes in APOE KO mouse
(compensate for APOE loss)

VS.
APOE KO
NORMAL
GeneCalling
AD “Rescue” Genes
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APOE GeneCalling Study
APOE3 form = normal
 ID mechanism whereby APOE4  AD

VS.
APOE3
APOE4
GeneCalling
Other AD Genes
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APOE in Alzheimer Disease
Predictive
Testing
Therapy
True Value
In Treating
Disease
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Summary
Today
Tomorrow
Diagnosis
Prediction
Treatment
Prevention
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What are the consequences
to the Global Healthcare?
How will the Healthcare look in the 21st
Century?
 The gate keeping role of patient-specific
information
 Selection of intervention method and
timing
 An integrated health management
approach

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Summary
Clear trends in Genetics and Predictive
Medicine will lead to broader options in
therapeutic interventions
 Traditional healthcare paradigm will be
impacted by new technologies and
ever-expanding disease knowledge
 An integrated approach could be a key
feature of 21st Century Healthcare

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