P h a rm a co G e n o m ics

Department Of
Bio-Informatics

Mirza Ahmed Hammad

Changing the world to

individual Drugs management
system
Roll No: 1255Session 2007-2011
 Pharmacogenomics
 The study of genome-derived data to predict
a body’s response to a drug or susceptibility to a
disease:
•
• Human genetic variation in DNA
– Single nucleotide polymorphisms (SNPs)
– Copy number differences
– Insertions
– Deletions
– Duplications
– Rearrangements
–
• RNA and protein expression differences
D ru g s co sts a re
e sca la tin g …!
Drug efficacy is questioned..
 UK ADRs Study

• 6.5% of new hospital admissions to internal

medicine wards are directly related to ADRs!
(1,225 admissions out of 18,820 during six
months)

•
• 4% of bed occupancy - directly due to ADRs

• Annual UK cost: EUR 706 million

(direct hospitalization costs - actual costs much
higher!)
• Women: 59% of ADRs (while only 52% of
admissions)

 All patients with same diagnosis

Remove:
(1) non-responders
(2) toxic responders

Treat:
Responders and Patients
Not Predisposed to Toxicity
Which is more urgent?

What should our priorities

be?
 Improving drug efficacy
Difficulties with ensuring better Drug


Efficacy:

• Tailoring the most effective drug and

dosage for the individual patient is
extremely complex.
(exception: in oncology – some success)

• Hundreds of polymorphic gene alleles are

involved

• Many non-genetic factors participate in

drug efficacy:
 Are we Ready for Personalized
Medicine?
Better Drug Efficacy? – Not Yet!
We are not yet ready, with few exceptions:

 - Oncology (Herceptin, anti-EGFR)

 - Depression (5-HTT genotyping)
 - High blood pressure – Bidil (FDA
approved June 2005)
(ethnic considerations in drug prescription as
an interim phase – ACE inhibitors ineffective
in African-Americans, preference for NO
donors & calcium channel inhibitors)

• In most medical disciplines, we are not likely

to be ready for Personalized Medicine in the
 (Almost) Ready for Personalized
Medicine –
If we focus first on better drug
safety– almost ready..
Consideration #1: Society


 - Growing public awareness on costs of

drug toxicity
(both economic costs and human suffering)


 - Growing awareness of genetic factors

affecting health
 for complex diseases (not just for
“genetic disorders”)

 (Almost) Ready for Personalized
Medicine
Consideration #2: Government – almost ready
Drug regulatory agencies are (almost) ready:

USA: In March 2005, the FDA has issued the

“Guidance for
Industry: Pharmacogenomic Data

Submissions”
http://www.fda.gov/cber/gdlns/pharmdtasub.ht

Europe: In February 2005, WHO/CIOMS

Working Group on
Pharmacogenetics has issued the report,

“Pharmacogenetics
Towards improving treatment with medicines”

(Council for International Organizations of Medical


 (Almost) Ready for Personalized
Medicine –
If we focus first on better drug
Consideration #3: safety
 Pharmaceutical Industry
• Pharma, which traditionally objected to PGx as
a threat
to market size and profits, begin to see the
advantages:
- Lower costs for clinical trials (less
participants)
- New “orphaned markets”
- Can charge more for safer drugs
- Marketing a diagnostic test along with
the drug
can bring added revenues
 (Almost) Ready for Personalized
Medicine –
If we focus first on better drug
safety
Consideration #4: Diagnostic Tools


• Diagnostic tools focusing on better drug

safety have been approved by the FDA
and the EC and are entering the market:

• Roche Diagnostics “AmpliChip P450”:

 - approved by the EC in September
2004, and by the FDA
 in December 2004

AmpliChip CYP450: CYP2D6 &
CYP2C19
 Current Practice: “Trial and
 Error”
• - What about Safety?

Toxicity No Effect

Oops!
Too Much Too Little

Decrease dose Increase dose

Favorable Effect

No effect
Toxicity
Increase dose
Decrease dose or change drug
or change drug
Drug Pharmacokinetics
 Depression
The most prevalent affective
disorder:
10%-20% of the population

(lifetime) Decreased raphe

serotonin
•
•
Excessive activity of
the serotonin
transporter??
•
 Health, Genes, & Society:
Where do we go from here?
• Should we oblige industry to do
'something' for people who do not
have the ‘right genotype’ for their
drug? What should it include?
•
• How can society ensure better
equality in healthcare, along with
individualization of
 pharmacotherapy?
 Personalized Medicine:
Not “if”, rather: “when?”
In your wallet by
2025?

Or maybe by 2050?

Opinion: This sort of card would initially (~2025?) include

mostly information related to drug metabolizing enzymes

Around ~2050 it might include an entire individual genome

(or at least, few millions SNPs..)
"Here's my sequence...” [New
AreYorker]
we ready?
Not quite yet! We need:
•Comprehensive data
•Affordable genotyping
tools
•Professional Education
•Solving ethical issues!
Meanwhile, we should
focus on improving drug
safely:
This is almost at hand!
 REFERENCES & Conclusion
• Although it is expected to take another decade for
PharmacoGenomics to be an accepted and
integral part of mainstream healthcare, but
with the help of other Biological groups
attached with the Genomes could catapult the
industry into the public consciousness. Drugs
based on individual testing can be more
effective giving required or near to required
results. For this there is a need of developing
new Biomarkers, Cell responses, Biotechnology
tools and Bio-Informatics tools, so that
diagnosis and screening of a disease could
easily be done.
•