Orion Corporation Orion Pharma 10.12.2008 1 Antti Haapalinna Nonclinical R&D Towards better risk management and theranostics with biomarker applications in drug discovery & development Antti Haapalinna, Ph.D. (Adjunct Professor) Director, Nonclinical R&D Orion Corporation R&D, ORION PHARMA BIO MEETS NANO AND IT 2008 9 th -11 th of December 2008. Oulu - Finland
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• Drug discovery and development is a long and expensive process
• Average total investment is > 500 to 800 M€/ approved product
“for every 5000 new compounds identified, only 250 enter preclinical trials and only one in ten of these drugs are approved.”
Presenter
Presentation Notes
27) High attrition To turn out just one to two products requires about a hundred discovery projects or approaches, involving upwards of 7 million compound tests in early screening assays. This level of screening produces about a thousand compounds with some of the criteria we are looking for. Follow-up molecular design and sophisticated biological testing narrows the number of development candidates. Once safety is confirmed in animal studies, compounds are advanced into human clinical trials where efficacy, safety and toleration are confirmed.
Probability of successwhen entering phase 10% 18 %
66%
Number on molecules under evaluation /phase required to achieve one product on market 8 5
1,5
(Compiled and modified from CRM international 2007 Pharmaceutical Factbook & from Pharma 2020 The vision. Which path will you take ? by PriceWaterhouseCoopers)
• Biological marker (Biomarker)A characteristic that is objectively measured and evaluated as an indicator of:
– Normal biological processes– Pathogenic processes– Pharmacologic responses to a therapeutic intervention.
Biomarkers definitions working group. Biomarkers and surrogate endpoints: Preferred definitions and conceptual framework. Clin Pharmacol Ther 2001;69(3):89-95.
Biomarkers may be genetic markers (sequence polymorphism); mRNA expression patterns; or protein markers, metabolites (clinical chemistry)… provided the biological relevance in relation to drug and disease (or toxic phenotype) are understood.
Pharmacogenomics: to identify variants enabling prediction of drug response including the occurrence of adverse reactions by systemic genomic analysis in
Clinical Pharmacology & Therapeutics (2008); 84, 3, 306–309 doi:10.1038/clpt.2008.114 Individual Genomes Instead of Race for Personalized Medicine PC Ng1, Q Zhao1, S Levy1, RL Strausberg1 and JC Venter11J. Craig Venter Institute, Rockville, Maryland, USA
Examples - PharmacogenomicsHERCEPTIN Trastuzumab (Genetech)Finding patients who will benefit from
treatment• a humanized monoclonal antibody
against the ERBB2 receptor that is approved for the treatment of breast cancer.
• To receive therapy diagnosed overexpression of ERBB2 receptor has to be shown
• New laboratory test: SPOT-Light® HER2 CISH™ Kit, FDA approval, Jul 1 2008
WARFARINFinding optimal dosing strategy• CYP2C9 (PK), vitamin K epoxide
reductase gene (VKORC1) (PD)• Account for 30-35% of the variability.
BUCINDOLOLFinding patients who will benefit from
treatment• ARCA Biopharma, NDA Busindolol to
heart failure (Sept 2008):• Researchers announced that the heart drug
bucindolol was able to reduce the risk of deathfor any cause among 38 percent of patients sharing a genetic variation in beta 1-adrenergic receptor, when compared to a placebo arm.
• Laboratory Corporation of America of Burlington and ARCA Discovery of Denver have entered into an exclusive collaboration to develop a commercial genetic test to aid in prescribing bucindolol (BT Catalyst, March-April, 2007)
– “…a genetically targeted heart failure drug in development by ARCA.”
Company Information (from web site)Laboratory Corporation of America® Holdings (LabCorp®) is much more than a routine clinical laboratory. As a pioneer in genomic testing and the commercialization of new diagnostic technologies, LabCorp is one of the world's largest clinical laboratories, with annual revenues of $4.1 billion in 2007. Headquartered in Burlington, North Carolina, LabCorp has approximately 26,000 employees and offers a broad range of genomic/esoteric tests. Listed under the ticker symbol LH on the New York Stock Exchange (NYSE), LabCorp tests more than 370,000 specimens daily for over 220,000 clients nationwide
Probability of successwhen entering phase 10% 18 %
66%
Number on molecules under evaluation /phase required to achieve one product on market 8 5
1,5
(Compiled and modified from CRM international 2007 Pharmaceutical Factbook & from Pharma 2020 The vision. Which path will you take ? by PriceWaterhouseCoopers)
Translational research, help for risk management ?
Verification of mechanism of drug actionPrediction of patient population to benefit of drug
Imagingcompany
Technologycompany
Diagnosticcompany
BioInform.comp
Disease ModelsCROs
Pharma-companies
Multiple stakeholders are needed to achieve world class breakthroughs
YES, but
Hospital Z
Increase understanding of biological mechanismsBetter prediction of drug pharmacokinetics and pharmacodynamics in vivo in humanImprove efficacy of the drug
Adjust dosing based on a biomarkerIdentify genetic markers for drug responseUse genetic tests to select responders for Phase III studies
Improve SafetyShorten development time and reduce development costs
Test for valid and probable valid biomarkersSupport claims in the application for a new drug