1. I MPACT OF P HARMACOGENOMICS ON THE P HARMACEUTICAL I NDUSTRY Viktoriya Buchko American Institute of Chemical Engineers August 6, 2008

2. Pharmacogenomics = drug therapy + genetic diagnostic test

3. O VERVIEW Relevance: realization in 5-10 years Especially because of the passage of Genetic Information Non-discrimination Act (GINA) 2008 Objectives: Increase safety and effectiveness of drugs Efficiency and economical concerns Do not exacerbate health disparity concerns

4. M ETHODOLOGY 0.1% genetic difference Limit market size Use biomarkers or other diagnostic tests

5. B ENEFITS Short-term Reduce side effects Reduce trial-and-error dosing Long-term Improve health care system Reduce health disparities

6. C URRENT P HARMACEUTICAL D RUG D EVELOPMENT M ODEL 2-3 years 3-5 years3-7 years Compound ID’ing Clinical Trials I: 20-30 healthy volunteers safety & dosage II: 100-300 patient volunteers efficacy & side effects III: 1000-15000 patient volunteers long-term use & ADRs Preclinical Studies -lab & animal testing -toxicity research -safety Examination -New Drug App.

7. D IFFICULTY IN D RUG D EVELOPMENT Increased R&D costs, yet fewer new drugs approved 9% of candidates filed for NDA 1/10 on market considered market success Competition from generics, “me-too” drugs

8. P HARMACOGENOMIC S OLUTIONS Decrease development time Faster approach to drug candidate identification Methods for approval New niches, such as anti-obesity drugs Rescue drugs Less risk

9. C ONCERNS WITH P HARMACOGENOMIC - BASED B USINESS M ODEL High-risk for large pharmaceutical companies Identifying genetic basis Post-marketing surveillance studies

10. POLICY ACTION TO FACILITATE PHARMACOGENOMICS Genetic test standardization Laboratory Test Improvement Act (S. 736) Integration of clinical and genomic data Genomics and Personalized Medicines Act (S. 976) Mitigate ethical concerns Distributive justice Selection & prioritization of drugs Enact the Institutional Review Board

11. Incentive for coupling diagnostic and drug treatment S. 976 calls for Nat’l Academy of Sciences for analysis Mandate Phase IV clinical trials POLICY ACTION TO FACILITATE PHARMACOGENOMICS

12. K EY F INDINGS Segmenting drug development industry Cooperation of large pharmaceutical companies with smaller biotech companies Immediate relevance in Mendelian one-gene- based diseases Genetic tests as diagnostics most pertinent in all- or-nothing benefit Genetic test to be first used in complement to a drug already on the market New uses for current drugs

13. C ONCLUSIONS With passage of GINA 2008, greater security in genetic testing will allow for the realization of personalized medicine. Must increase regulatory control to keep pace with the developing pharmacogenomic-based drugs. Increase public awareness, including that of physicians, of the possibilities of safer, more efficacious drug treatments.

14. Q UESTIONS

15. B I D IL : TO REDUCE HEART FAILURE IN SELF - IDENTIFIED BLACK INDIVIDUALS Twice the fatality rate in black individuals than other Americans Reduce disparity through minority recruitment Reduce mortality rate by 43%, 1 st hospitalization rate by 33% Statistic valid for 45-64 year olds, where only 6% of mortality population is accounted for Commercial tactic to obtain new patent Self-identification is not proof of genetic basis Assessment of disparities in population targeting Level of significance to determine variation within group Off-labeling present? Follow-up genetic studies PROOFCRITICISM

16. I MPLICATIONS OF GENETIC TESTING Access predictive info Constraints Issues with direct-to-consumer genetic tests Method of administration