An Overview of

An Overview of
Personalised
Personalised
Medicines
Medicines
Eddie Blair Eddie Blair
Managing Director Managing Director
Integrated Medicines
www.integratedmedicines.co.uk
eddie.blair@integratedmedicines.co.uk
Content
1. Definitions
2. Examples
3. Relationships
Content
1. Definitions
2. Examples
3. Relationships
PATIENT-TARGETED
THERAPIES
INNOVATIVE
MEDICINES
THERAPEUTIC
NEED
Right Medicine
Right Patient
Right Disease
Right Time
Right Dose
Right Response
What is Personalised Medicine?
PATIENT-TARGETED
THERAPIES
INNOVATIVE
MEDICINES
THERAPEUTIC
NEED
Right Medicine
Right Patient
Right Disease
Right Time
Right Dose
Right Response
Right Price
What is Personalised Medicine?
Personalised medicines ..
convert Pharmaceuticals
to
Pharmasuitables*
*George Poste, Cambridge, April 2003
Personalised medicines ..
convert Pharmaceuticals
to
Pharmasuitables*
but
era of personalised medicines will
not be with us for at least another 15
to 20 years**
*George Poste, Cambridge, April 2003 ** Weatherall et al (2005)
Safety and efficacy
Keys issues with
medicines today
are ..
*
*5
th
12
th
September 2005
Personalized Medicine could ...
Improve patient
outcomes
Speed of
development of
drugs & tests
Improve cost:
benefit ratio
How personalised can medicine become?
Personalised Medicine is not
Preferred Definition (1)*
Biological marker (biomarker): A characteristic
that is objectively measured and evaluated as an
indicator of normal biological processes, of pathogenic
processes, or of pharmacologic responses to a
therapeutic intervention
**Biomarker types: Disease Staging
Efficacy Surrogate (clinical outcome)
Translational Toxicity
Mechanism Target
*http://ospp.od.nih.gov/biomarkers; ** Boguslavsky J, Drug Disc Dev 2004
Preferred Definitions (2)*
Surrogate endpoint: A biomarker that is intended to
substitute for a clinical endpoint. A surrogate endpoint
is expected to predict clinical benefit (or harm or lack
of benefit or harm) based on epidaemiologic,
therapeutic, patho-physiologic, or other scientific
evidence.
Clinical endpoint: A characteristic or variable that
reflects how a patient feels, functions, or survives.
*http://ospp.od.nih.gov/biomarkers/
Working Definitions (3)
Diagnostic:
A test (or set of tests) which determines the
presence or absence of a specific disease
Prognostic:
A test (or set of tests) which indicates the
probability of developing a specific disease or the
likely progression of an existing disease.
Theranostic:
Predictive: A test (or set of tests) that indicates
the likely outcome of an intervention
Monitoring: A test (or set of tests) that objectively
reports on response to intervention
Prognostic
How is the disease likely
to progress
in the patient?
Biomarker
Discovery what biological
parameters are changed?
Validation are these
changes reproducible?
Surrogate
Clinical - does the disease status
appear to be changing?
PK/PD - does the lack of response reflect no
efficacy or poor pharmacology?
Diagnostic
Does the patient
have a specific disease?
The test continuum
Working Definitions** (4)
Pharmacogenetics*:
Examines the differential effects of a drug in vivo that
are dependent on inherited gene variants
Assessed by genetic approaches (SNPs or haplotypes {linked SNPs})
E.g., Abacavir rash & HLA variation; Cyt P450 & metabolism
Pharmacogenomics*:
Examines the differential effects of compounds - in
vitro or in vivo - on the expressed genome
Usually assessed by analysing mRNA or protein expression patterns
E.g., OvarC transcription profiles, cardiovascular disease proteomic
profiling
*After Lindpainter, Nature Reviews in Drug Discovery June 2002.
**See also http://www.emea.eu.int/pdfs/human/press/pp/307001en.pdf
Position paper on terminology in pharmacogenetics November 2002
Content
1. Definitions
2. Examples
3. Relationships
Integrated medicines and testing
Examples of Companion Programmes
Oncology:
Herceptin (Roche/Genentech) + Herceptest (DAKO)
Gleevec (Novartis) + BCR-Abl Gene Mutations
Tarceva (Roche) & IRESSA (AstraZeneca) with
Genzyme's EGFR Mutation Assay (28SEP05)
Infectives:
Sepsis (endotoxin + antibiotic)
HIV (RTI, PRI + genotyping)
HCV (genotypes re: sustained response to interferons)
Cardiovascular:
Lovenox (Aventis) + Enox (Pharmanetics)
Cholesterol lowering statins + cholesterol tests
LpPLA
2
(Diadexus) and SB480848 (GSK) for athero
Examples of Companion Programmes
(cont)
Other:
Toxicity/metabolism: Warfarin, mercaptopurine
Metabolic Disease (glucose > HbA1c)
Urology (PSA test)
Respiratory (breath dx)
Osteoporosis (bone mass density for
bisphosphonate treatment)
Unmet needs
Neurosciences (Alzheimers, Parkinsons)
Imaging modalities!? See Frank (2003)
Content
1. Definitions
2. Examples
3. Relationships
A Healthcare Value Net*
Government/
Regulators/ Payors
Direct healthcare
providers
Industry Pharma
cos & associated
value-chain, eg, Dx
Co
Patient
(consumer/
beneficiary
of healthcare)
*Brandenberger & Nalebuff, 1995
A Healthcare Value Net
Government/
Regulators/ payors
Direct healthcare
providers
Industry Pharma
cos & associated
value-chain, eg, Dx
Co
Patient
(consumer/
beneficiary
of healthcare)
Timelines for Diagnostic and Medicine
Development
Concurrent FDA
approval
Discovery
Pre-clinical
Phase I
Phase II
Phase III
FDA Review
Project
Initiation
8 years 15 years
Drug
Development
Diagnostic
Development
Marker Discovery
Test Development
Regulatory Review
Latest date to
begin companion
test programme
Value to Pharma: Competitive Advantage
Faster to market
or Faster to
Decision
Faster to market
or Faster to
Decision
Time -years
0
5
10
Sales
Adaptation: Gilham, Drug Discovery World Fall 2002
Enhanced peak
sales
Extended life cycle
Reduced time to
peak sales
VPC no Companion Test
Discounted Cash Flow - No Dx, NPV = $900 (15% dcf)
-1000
-500
0
500
1000
1500
2000
2500
2005 2006 2007 2008 2009 2010 2011 2012 2013 2014 2015 2016 2017 2018 2019 2020
Year
R
e
v
e
n
u
e

&

C
o
s
t
s
Revenue Costs
Net Present Value is increased by $1809MM c/o test
VPC With Companion Test
Discounted Cash Flow - Companion Dx, NPV = $2,694 (10% dcf)
-1000
-500
0
500
1000
1500
2000
2500
2005 2006 2007 2008 2009 2010 2011 2012 2013 2014 2015 2016 2017 2018 2019 2020
R
e
v
e
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&

C
o
s
t
s
Year
Revenue Additional Revenue Costs Dx test
How could the NPV be apportioned in a Dx-
Rx deal?
Diagnostics Partner Revenue & Costs
-500.00
0.00
500.00
1000.00
1500.00
2000.00
2500.00
2
0
0
5
2
0
0
6
2
0
0
7
2
0
0
8
2
0
0
9
2
0
1
0
2
0
1
1
2
0
1
2
2
0
1
3
2
0
1
4
2
0
1
5
2
0
1
6
2
0
1
7
2
0
1
8
2
0
1
9
2
0
2
0
Year
R
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v
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&

C
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t
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Pharma Partner Revenues & Costs
-1000
-500
0
500
1000
1500
2000
2500
2005 2006 2007 2008 2009 2010 2011 2012 2013 2014 2015 2016 2017 2018 2019 2020
Year
R
e
v
e
n
u
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&

C
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t
s
Discounted Cash Flow - Companion Dx, NPV = $2,694 (10% dcf)
-1000
-500
0
500
1000
1500
2000
2500
2005 2006 2007 2008 2009 2010 2011 2012 2013 2014 2015 2016 2017 2018 2019 2020
R
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v
e
n
u
e

&

C
o
s
t
s
Year
Revenue Additional Revenue Costs Dx test
Dx NPV = $84 M
Rx NPV = $2,610 M
Diagnostics Partner Power
( Pharmaceutical Partner Urgency)
Lo Hi
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Turnaround
Outcome: Product
Rescue
Use-to-order
Outcome: Market
expansion
Make-to-order
Outcome: Market
penetration
Integrated
Outcome: Co-
developed test &
medicine
PharmaCo-DxCo Relationships*
*Little & Blair, 2005
Why do pharma companies need new
relationships?
Metrics suggest that
fewer than 1 in 10
entities entering
clinical trials make
it to the markets
AND
some of those that
do make it face
withdrawal and
litigation ($253M
Vioxx verdict!?)
A Healthcare Value Net
Government/
Regulators/ Payors
Direct healthcare
providers
Industry Pharma
cos & associated
value-chain, eg, Dx
Co
Patient
(consumer/
beneficiary
of healthcare)
British Medical Journal 1999;319 (18 September):762.
Relationships
Patient information
Policing the quality of information that is available
to patients via the Internet
Quality assured Medicine Guides c/o the
Medicines Information Project (MIP) at
www.medicines.org.uk
Royal Society initiative on the Impact of ICT on
health and healthcare
EFPIA: The Informed Patient - The Value Of
Health Information (SEP05)
Individual pharma companies: medicines specific
websites.
CPD for Medical Practitioners
From GMC website (http://www.gmc-
uk.org/med_ed/default.htm, accessed 19SEP05)
Does patient-centredness improve patient care
or safety?
NHS National Genetics Education and
Development Centre
Nuffield Centre for Bioethics Pharmacogenetics:
Ethical Issues (SEPT03)
Royal Society initiatives on (1) Personalised
medicines: hopes and realities (21SEP05); (2)
Pharmacogenetics Dialogue; and (3) Genetics &
Health
Training in translational medicine
A Healthcare Value Net
Government/
Regulators/ Payors
Direct healthcare
providers
Industry Pharma
cos & associated
value-chain, eg, Dx
Co
Patient
(consumer/
beneficiary
of healthcare)
Regulators Output .
FDA in March/ April 2005
Guidance on pharmacogenetic testing in clinical trials
(http://www.fda.gov/cder/guidance/6400fnl.pdf)
Concept paper on co-development of medicines and
diagnostics
(www.fda.gov/cder/genomics/pharmacoconceptfn.pdf)
Medical imaging in drug development
(http://www.fda.gov/cder/regulatory/medImaging/default.htm)
EMEA in March 2005
CMPH Guidelines on pharmacogenetics
(www.emea.eu.int/pdfs/human/pharmacogenetics/2022704en
.pdf)
Japan
Guideline on "Ethics Guidelines for Human Genome / Gene
Analysis Research 29MAR01 in English from Ministry of
Health, Labour and Welfare.
Full amendment 28DEC04 and partial amendment
29JUN05: no translation yet available.
EU Regulation of genetic sample collection
for clinical trials*
Survey carried out in
2001** showed different
regulations for PGx
sample collection
1. Separate informed consent
2. Anonymisation of samples
3. Genes studied specified
4. Method used specified
5. Retention controlled
* Ruth March
** Theilade et al (2001)
Key political/legal/ethical issues .
Harmonisation
Re-imbursement
Geography
Culture
Expectations
Education
Flexible pricing
Can everyone be on-message?
Key skills in enabling the realisation of
personalised medicines
Relationship management
Risk management
Planning
Knowledge
Durability and/or flexibility
Cash flow
Patience 20 years isnt such a long
time
Eddie Blair
Integrated Medicines Ltd
eddie.blair@integratedmedicines.co.uk
www.integratedmedicines.co.uk
Thank you
Any questions?