Integration of Pharmacogenomics In To Clinical Trials

By Yawo M Akrodou PHD

MS Clinical Research Administration

Walden University June 2016

Presentation Overview

Definition of Pharmacogenomics

Causes of Using Pharmacogenomics in Clinical Trial

Contributions of Pharmacogenomics

Limitation of Pharmacogenomics

Challenges of Pharmacogenomics

Advancing Pharmacogenetics

Prospective of Pharmacogenetics

Recommendation

Conclusions

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Pharmacogenomics use in clinical trials,

is it Worthy?

© 2014 Walden University, LLC

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Definition: Pharmacogenomics Concepts

• Mixing of pharmacology and genetics practices

• Investigating various drug responses due to genes

• Prediction of genetics reactions to drug side effect and adverse

• Making drug according to genetic information

• Individualization of drug therapy

• One Drug Does Not Fit All”

• Process to get the right drug to right patient

(Issa, 2000)

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Definition: Pharmacogenomics Methods

• Use of the DNA/RNA or protein sequencing tool strategy to

develop reliable markers that may help to predict drug

responses

• Use of protein sequencing to catalogue biomarker of specifics

drug response in disease treatment for drug discovery

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Definition: Pharmacogenetics' Methods

• The study of inherited factors and their influence on drug

response variability

• Use genes sequencing result to discover drugs

(Cohen, 2008)

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Causes of Using Pharmacogenomics in Clinical Trial :

Pharmaceutical Industry Challenges

Increase of drug recalls from the markets

Failure to make new drug safe and effective

Long period of clinical trial conducts (i.e.12 years)

Financial burden of clinical trial organization

Regulatory pressure on drug making industry

Globalization fueling competition

Need to make drug for complex disease

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Causes of Using Pharmacogenomics in Clinical Trial : Classic

Clinical Trial Limitation

• Use of pharmacology limited process

• Use of chemical-driven limited methods

• Cannot predict genetic induced drug reaction

• Hypothesis driven strategy

• Lack to detect all pre-market drug side effect

• Lack of knowledge of inter-individual drug responses

• Produce drugs with high individual incidence

• Obsoletes strategy and limited innovation

• Fig 1. Clinical trial of new drugs. Source : Shaw, D.D.(2013).

•

Fig 1. Clinical trial of new drugs. Source : Shaw, D.D.(2013).

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Causes of Using Pharmacogenomics:

Increasing Emerging Genetic Disorder

Source: Szade, et al.2013

Contributions of Pharmacogenomics: Innovation of Drug

Discovery Process

• Innovation of drug discovery

• Targeted drug development

• Solve inter-individual drug responses

• Tailoring drug therapy to individual

• Individualized drug uses

• Reduce drug interaction incidence

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Limitation of Pharmacogenomics

• Cannot cure all diseases

• Gene-gene interaction

• Gene regulation anomalies

• Unforeseen mutation

• Higher number of genes in multigene etiology

• Limitation of genes sequencing and profiling

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Contributions of Pharmacogenomics: Quality Drug Making

• Make drugs according to genes

variants

• Adjusting drug-doses according

• to genetic variants

• Provide drug according to genetic

deficiencies in :

Receptors,

Metabolizer

Transporter

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Figure3 . Example of gene therapy of ADA

defiecieny. Source .Szade, et al.(2013)

Contributions of Pharmacogenomics: Monogenic and Multigene

Treatment

Monogenic disease treatment

– Transduction method

– Transgene method

– Enzyme replacement

Figure2 : One of the first controlled trial of genes therapy in 1990

Source: Szade, et al.2013

Multigene Treatment

– Genes interaction test treatment

– Genes therapy to enhance treatment

10-20% pharmacogenomics treatment of

Parkinson’s Disease

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Challenges of Pharmacogenomics

• Lack of uniform method across biotech companies for DNA

treatment

• Lack of regulatory for patient safety and privacy information

protection

• Non uniform methodology for data process

• Complex of genomics and genetic application

• Unknown cost-effectiveness

• Lack of Education

• (Gudmundur, Thorisson, & Brookes, 2009).

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Advancing Pharmacogenetics: Best Pharmacogenomics Practices

• Use of genomics practices:

– Predict lead compounds reaction candidate genes in preclinical

trial

– Determine earlier subgroup genetic reaction to the compound in

clinical trial Phase I & II.

– Gather extensive data for drug registration and beyond phases

III, IV and V.

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Advancing Pharmacogenetics

Advocate for more FDA and ICH Framework establishments

Encourage the Industry of Pharmacogenomics Working Group

(I-PWG) and Personalized Medicine Initiative to have uniform

regulation and pharmacogenomics working method.

Continual cost-effectiveness assessment

Stakeholder education

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Social Implications

Enhancement of individual health

Revive Pharmacy-business

Increase drug access

Decrease health disparity

Promote new era of individualized treatments (Glass,et

al,2000)

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Prospective of Pharmacogenetics

Prospective

• Promising future

• Opportunity for drug discovery and development Innovation

• High level of cost-effectiveness

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Prospective of Pharmacogenetics

Develop rigorous methods for sample and data collection

Create general consent for proper information disclosure and

recruitment

Develop a protocol template which satisfies regulatory and

ethical standards

Devise the transparent methodology for statistical data analysis

and their translational process into clinical

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Conclusion

• Pharmacogenetics drug developments, although bearing

scientific promise, raise ethical concerns about conducting

research with human subjects, particularly as regards

confidentiality, risk–benefit analysis, DNA-banking.

• In addition, pharmacoeconomic issues remain to be resolved,

but pharmacogenetics and pharmacogenomics hold a

promising future and the potential to innovate the drug

discovery process (Issa, 2002).

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References

Cockburn, M. L. (2004). The changing structure of the pharmaceutical industry drug development

under today's new institutional arrangement. Health Affair. 23(1),10-22

doi: 10.1377/hlthaff.23.1.10

Cohen, N. (2008). Pharmacogenomics and Personalized Medicine. Louisville, KY: Humana

Press.

Issa, M. A. (2002). Ethical perspectives on pharmacogenomics profiling in the drug development

process. Reviews Drug Discovery .1(4),300-308. doi:10.1038/nrd771

Glass, W.G., McDermott, D. H., & Lim, J. K., Lekhong, S., Yu, F. S., Frank, A. W…. (2006).

CCR5 deficiency increases risk of symptomaticWest Nile virus infection. Journal of

Experimental Medicine, 203(1), 35–40

Gudmundur, A., Thorisson, J. M., & Brookes, A. J. (2009). Genotype–phenotype databases:

Challenges and solutions for the post-genomic era. Nature Reviews Genetics 10(1), 9–18.

doi:10.1038/nrg2483Szade K, Bukowska-Strakova K, Nowak WN, Szade A, Kachamakova-Trojanowska N, Zukowska

M, et al…… (2013) Murine Bone Marrow Lin−Sca-1+CD45− Very Small Embryonic-Like

(VSEL) Cells Are Heterogeneous Population Lacking Oct-4A Expression. PLoS ONE 8(5):

e63329. doi:10.1371/journal.pone.0063329

Shaw, D.D.(2013).Clinical Trial Phases. MSCreation.Retrieved from http://mscreations.org/clinical-trial-phases

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Acknowledgement

I would like to thank our Instructor for making

this presentation possible.

Dr. Shazia Qureshy

Thank you very much.

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