礼来公司在fda的演讲：择思达县与pgx.pptVIP

Richard D. Hockett, Jr. M.D. Sr. Clinical Research Physician Group Leader, Genomic Medicine Pharmacogenetics Pharmacogenomics The Promise of Pharmacogenomics Pharmacogenomics will radically change the manner in which we develop drugs. Soon, we will be able to get the right drug into the right patient. Applying pharmacogenomics to drug development will cut cycle times to 1.5 - 2 years. Pharmacogenomics will be able to bring removed drugs back on the market, by predicting who is susceptible to adverse events. Pharmacogenomics: applications and key activities Genetics in Drug Development Genetic Changes as Biomarkers Disease Susceptibility Biomarkers Single Disease Genes (Mendelian Inheritance) Genetic Associations in Complex Diseases Genetic Changes Associated with Tumorogenesis Inherited Mutations Spontaneous Mutations in the Tumor Multiple Transcript Changes Leading to Reclassification Drug Activity Biomarkers Genetic Polymorphisms Predicting Drug Metabolism DNA Variations Predicting Drug Response DNA Variations Predicting Adverse Events Genetic in drug development Conditions when Lilly would choose to include genetics in drug development Early phase development (Candidate selection through phase II) Animal toxicity profile to predict human toxicity Mechanism of action Early target/receptor interaction and PK/PD effects Phase III/Phase IV development When medically necessary Safety issue When test can differentiate drug Better response profile Adverse event management Strattera and CYP2D6 Metabolism Primarily metabolized by CYP2D6 Plasma clearance EM 0.35 L/hr/kg PM 0.03 L/hr/kg AUC PM:EM 10 fold difference T1/2 EM 5.2 hours PM 21.6 hours Safety vs Tolerability vs Efficacy Issues Interplay has impact on label Empirical Bayesian Estimates of Clearance for each Patient in Population PK Analysis CYP2D6 Polymorphisms: Assessing Safety Initial clinical pharmacology studies above proposed maximum dose CYP2D6 genotype obtained under double-blind condi