Current PharmacoGenomics

8/7/2019 Current PharmacoGenomics

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Mirza Ahmed Hammad

Changing the world to

individual Drugs managementsystem

Ph a rm acoG e n o m ics

:Roll No 1255 -Session 2007 2011

D

e p a r t m e n t

O f

-

B i o

I n f o r m a t

i c s


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Pharmacogenomics

The study of genome-derived data to predicta bodys response to a drug or susceptibility to adisease:

Human genetic variation in DNA Single nucleotide polymorphisms (SNPs) Copy number differences Insertions Deletions

Duplications Rearrangements

RNA and protein expression differences


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D rugs costs are

! e sca la tin g


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..Drug efficacy is questioned


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UK ADRs Study

6.5% of new hospital admissions to internalmedicine wards are directly related to ADRs!(1,225 admissions out

of 18,820 during sixmonths)

4% of bed occupancy - directly due to ADRs

Annual UK cost: EUR 706 million(direct hospitalization costs - actual costs muchhigher!)

Women: 59% of ADRs (while only 52% of admissions)


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:Treat Responders and Patients

Not Predisposed to Toxicity

l l pat ients with same diagnosis

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

Which is more urgent?

What should our prioritiesbe?


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Improving drug efficacy Difficulties with ensuring better Drug

Efficacy:

Tailoring the most effective drug anddosage for the individual patient isextremely complex.(exception: in oncology some success)

Hundreds of polymorphic gene alleles areinvolved

Many non-genetic factors participate indrug efficacy:


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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 (FDAapproved June 2005)(ethnic considerations in drug prescription asan interim phase ACE inhibitors ineffectivein African-Americans, preference for NOdonors & calcium channel inhibitors)

In most medical disciplines, we are not likelyto be ready for Personalized Medicine in the


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Medicine If we focus first on better drug

safety Consideration #1: Society almost ready..- Growing public awareness on costs of

drug toxicity(both economic costs and human suffering)

- Growing awareness of genetic factorsaffecting health

for complex diseases (not just forgenetic disorders)


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(Almost) Ready for Personalized Medicine

Consideration #2: Government almost read

Drug regulatory agencies are (almost) ready:USA: In March 2005, the FDA has issued the

Guidance forIndustry: Pharmacogenomic Data

Submissionshttp://www.fda.gov/cber/gdlns/pharmdtasub.h

Europe: In February 2005, WHO/CIOMSWorking Group onPharmacogenetics has issued the report,

Pharmacogenetics

Towards improving treatment with medicines(Council for International Organizations of Medical
http://www.fda.gov/cber/gdlns/pharmdtasub.htmhttp://www.fda.gov/cber/gdlns/pharmdtasub.htm


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safety Consideration #3: Pharmaceutical Industry Pharma, which traditionally objected to PGx a

a threat

to market size and profits, begin to see theadvantages:

- Lower costs for clinical trials (lessparticipants)

- New orphaned markets- Can charge more for safer drugs

- Marketing a diagnostic test along withthe drug

can bring added revenues


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safety Consideration #4: Diagnostic Tools Diagnostic tools focusing on better drug

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

Roche Diagnostics AmpliChip P450:- approved by the EC in September

2004, and by the FDAin December 2004


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AmpliChip CYP450: CYP2D6 &CYP2C19


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urren rac ce: r a anError

- What about Safety?

Toxicity No Effect

!Oops!Oops Too Much Too Little

Decrease dose Increase dose

No effect

Increase dose or change drug

Toxicity

Decrease dose or change drug

Favorable Effect


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Drug Pharmacokinetics


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Depression The most prevalent affective

disorder:10%-20% of the population

(lifetime)

Decreased raphe serotonin

Excessive activity of the serotonin

transporter??


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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 theirdrug? What should it include?

How can society ensure betterequality in healthcare, along withindividualization of

pharmacotherapy?


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: Personalized Medicine

, : Not if rather when?

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

In your wallet by2025?

Or maybe by 2050?

N


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... NewYorker]

Are we ready?! :Not quite yet We need

Comprehensive data Affordable genotyping

tools

Professional Education !Solving ethical issues

,Meanwhile we should focus on improving drugsafely :

!This is almost at hand


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REFERENCES & Conclusion

Although it is expected to take another decade forPharmacoGenomics to be an accepted andintegral part of mainstream healthcare, butwith the help of other Biological groupsattached with the Genomes could catapult theindustry into the public consciousness. Drugsbased on individual testing can be moreeffective giving required or near to requiredresults. For this there is a need of developing

new Biomarkers, Cell responses, Biotechnologytools and Bio-Informatics tools, so thatdiagnosis and screening of a disease couldeasily be done.

Current PharmacoGenomics

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