Personalized Medicine & Treatments

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1 Personalized Medicine & Treatments NASCHIP September 14, 2007 Teresa DeLuca, MD, MBA Vice President Department of Personalized Medicine Medco is a registered trademark of Medco Health Solutions, Inc.

2 Pipeline Management 2007 Specialty Pipeline Drugs Specialty Pipeline Mircera Anemia Torisel Renal Cell Carcinoma Cimzia Crohn s Disease Efaproxyn Breast Cancer Brain Metastasis Tasigna Chronic Myeloid Leukemia Spheramine Advanced Parkinson s Ambrisentan Pulmonary Arterial Hypertension Thelin Pulmonary Arterial Hypertension Kiacta Amyloid Amyloidosis Tykerb Breast Cancer Metastasis Vatalanib Colorectal Cancer drugs in pipeline 45% of drugs in clinical trials for new indications are specialty 21% of pipeline drugs through 2007 are specialty Sources: FDC Reports. NDA Pipeline. FDC Reports. The Pink Sheet. R&D Insight.

3 Pipeline drugs with pharmacogenomic profiles Drug Use Possible test Comment Maraviroc HIV CCR5 viral tropism Greater viral suppression against viral strains using CCR5 surface protein for cell entry Iloperidone Schizophrenia Undisclosed gene polymorphism Greater response among patients with the gene polymorphism Desvenlafaxine Depression Metabolizer status of CYP2D6 Action of drug may be affected by poor or ultrarapid metabolizer status Indacaterol Asthma/COPD Genetic testing for polymorphism at beta-adrenergic receptors Polymorphism at beta-adrenergic receptors may affect drug action Bucindolol Heart failure B1 AR389 gene polymorphism Polymorphism may affect response to beta-blockers (hospitalization/ mortality) Vatalanib Colorectal cancer Metabolizer status of CYP2D6 Action of drug may be affected by poor or ultrarapid metabolizer status Sources: The Royal Society. Personalised Medicines: Hopes and Realities. London: The Royal Society; Drug Trend Report, 2006, p

4 General approaches to personalized medicine with pharmaceuticals and biologics Predictive Target diagnostics Toxicity/ metabolism = = Identify responders vs. non-responders for a specific drug Identify slow/fast metabolizers or patients who develop severe toxicity Her 2 BCR ABL CYP 450 UGT 1A1 TPMT Prognostic Pathway = Identify the key markers that define the course of disease and therefore could guide different pathway therapies. (hormone Tx vs. chemo Tx) Oncotype Dx MammaPrint 4

5 Prevalence of people taking medications metabolized by the liver enzymes 5 Liver enzymes CYP2D6 CYP2C9 CYP2C19 Examples of drugs and drug categories Atomoxetine (Strattera ) Tamoxifen Proton-pump inhibitors (PPIs) Warfarin Non-steroidal antiinflammatory drugs (NSAIDs) Oral hypoglycemics Antidepressants Antipsychotics Beta-blockers Prevalence of members 20.24% 19.31% 14.82% Total 36.09% Source: Medco Data, 2006.

6 Warfarin-associated hospitalizations CYP2C9 + VKORC1 Risk associated with dose adjustment and any hemorrhage/thrombosis hospitalization event 1 Testing for warfarin metabolism rate may reduce risk for hospitalization associated with hemorrhage or thrombosis Dose adjustment 1 N 1,214 IP event rate 19.60% Testing may reduce the number of dose adjustments required Greater dose adjustments = greater risk for hospitalization 2 or more Total 319 1, % 21.92% FDA Advisory Committee agrees with genetic testing for warfarin 2 Sources: 1. Medco data, FDA Advisory Committee; fda.gov/cder/genomics. April 26,

7 Tamoxifen effectiveness in breast cancer by CYP450 2D6 phenotype Time to relapse Relapse-free survival % EM IM PM % EM IM PM 20 P= Year after randomization 20 P= Year after randomization Disease-free survival 100 Overall survival EM % IM 40 PM 20 P= Year after randomization Source: Goetz et al. Breast Cancer Res Treat. 2007; 101: % 80 EM 60 IM 40 PM 20 P= Year after randomization

8 Questions / discussion 8