Role of Pharmacogenomics in Drug Development – An Industry ...

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PGx reveals efficacy for rosiglitazone inAlzheimer’s Disease (AD)• PPARγ agonist approved for the treatment of Type 2 Diabetes• Rationale in AD– Decline in cerebral glucose utilisation linked to AD progression– PPARγ agonists may increase glucose brain entry and utilization– Positive cognitive effect in pilot study (n=30)• Phase II, 24 week placebo controlled, dose ranging study of rosiglitazoneefficacy in mild to moderate AD patients• DNA samples collected for PGx analysis of rosiglitazone response followingstratification of APOE4 carriage– APOE ε4 positive & APOE ε4 negative• Clinical study results published– Risner et al, Pharmacogenomics Journal, 2006; doi:1038/sj.tpj.6500369
APOE4 - a susceptibility gene variant forcommon forms of Alzheimer diseaseProportion of eachgenotype unaffected1.00.82/30.62/43/30.43/40.24/4060 65 70 75 80 85Age at onsetMean age ofonset ofAlzheimerdisease as afunction of theinheritance of thefive commonAPOE genotypes
Page 1 and 2: Role of Pharmacogenomics inDrug Dev
Page 3 and 4: Variation in medicine response to c
Page 5 and 6: GSK Pharmacogenetic StrategyOngoing
Page 7: Efficacy PGx: Opportunities• Asso
Page 11 and 12: ADAS-Cog Score in APOE ε4-Negative
Page 13 and 14: Rosiglitazone in ADPhase III progre
Page 15 and 16: Abacavir and Hypersensitivity (HSR)
Page 17 and 18: Abacavir HSR Prospective PGx study
Page 19 and 20: PPARγ agonist FarglitazarOedema AE
Page 21 and 22: Farglitazar oedema AE PGxSCNN1B Gen
Page 23 and 24: Ethical considerations• PGx is no

Role of Pharmacogenomics in Drug Development – An Industry ...

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