Current PharmacoGenomics 1

8/7/2019 Current PharmacoGenomics 1

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Mirza Ahmed Hammad

Changing the world to

individual Drugs managementsystem

PharmacoGenomics

Roll No: 1255 Session 2007-2011

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Pharmacogenomics

The study of genome-derived data to predict abodys 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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Drugs costs are

escalating!


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Drug efficacy is questioned..


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UK ADRs Study

6.5% of new hospital admissions to internal medicinewards are directly related to ADRs!(1,225 admi

ssions 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 muchhigher!)

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

Pirmohamed et al (July 2004) Adverse drug reactions as cause of admission tohospital: prospective analysis of 18 820 patients. BMJ. 329:15-19.


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Treat:

Responders and PatientsNot Predisposed to Toxicity

All patients with same diagnosis

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

Which is more urgent?

What should our prioritiesbe?


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Improving drug efficacyDifficulties with ensuring better Drug Efficacy:

Tailoring the most effective drug and dosage for theindividual patient is extremely complex.(exception: in oncology some success)

Hundreds of polymorphic gene alleles are involved

Many non-genetic factors participate in drugefficacy:

Gender; age; environment; diet; physical activity;smoking; family support etc.

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Are we Ready for PersonalizedMedicine?

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 interimphase 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 clinic before 2025;maybe only ~2050? but there will be exceptions..


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Medicine

If we focus first on better drug

safetyConsideration #1: Society almost ready..- 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)

- Worries about the graying of society and theassociated soaring health care costs in the EU and USA


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(Almost) Ready for PersonalizedMedicineConsideration #2: Government almost ready

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

Guidance forIndustry: Pharmacogenomic Data Submissions

http://www.fda.gov/cber/gdlns/pharmdtasub.htm

Europe: In February 2005, WHO/CIOMS WorkingGroup on

Pharmacogenetics has issued the report,Pharmacogenetics

Towards improving treatment with medicines(Council for International Organizations of Medical

Sciences)
http://www.fda.gov/cber/gdlns/pharmdtasub.htmhttp://www.fda.gov/cber/gdlns/pharmdtasub.htm


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Medicine


safetyConsideration #3: 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 drugcan bring added revenues


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Medicine


safetyConsideration #4: Diagnostic Tools

Diagnostic tools focusing on better drug

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

Roche Diagnostics AmpliChip P450:

- approved by the EC in September 2004,and by the FDA

in 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 doseor change drug

Toxicity

Decrease doseor change drug

Favorable Effect


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Drug Pharmacokinetics


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DepressionThe most prevalent affective disorder:

10%-20% of the population (lifetime)

Decreased rapheserotonin

Excessive activity ofthe serotonintransporter??


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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 better equalityin healthcare, along withindividualization of

pharmacotherapy?


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Personalized Medicine:

Not if, rather: when?

Opinion: This sort of card would initially (~2025?) includemostly information related to drug metabolizing enzymes

Around ~2050 it might include an entire individualgenome(or at least, few millions SNPs..)

In your wallet by2025?

Or maybe by 2050?

[New


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ere s my sequence... [NewYorker]Are we ready?

Not quite yet! Weneed: Comprehensive data

Affordablegenotyping tools Professional

Education Solving ethical issues!

Meanwhile, we should


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REFERENCES & Conclusion Although it is expected to take another decade for

PharmacoGenomics to be an accepted and integral part ofmainstream healthcare, but with the help of other Biologicalgroups attached with the Genomes could catapult theindustry into the public consciousness. Drugs based onindividual testing can be more effective giving required or

near to required results. For this there is a need of developingnew Biomarkers, Cell responses, Biotechnology tools and Bio-Informatics tools, so that diagnosis and screening of a diseasecould easily be done.

References are given with CD.

Thanks!

Documents

Current PharmacoGenomics 1