1. CRESTOR ® (ZD4522, rosuvastatin calcium) TABLETS Comments on Efficacy Joy Mele FDA Statistical Reviewer Division of Biometrics 2 Joy Mele FDA Statistical Reviewer Division of Biometrics 2 Center for Drug Evaluation and Research

2. 2 Comments on Efficacy Rosuvastatin Effect on LDL –Studies 8, 33 and 65 Comparison of Rosuvastatin and Atorvastatin –Studies 33 and 65 Rosuvastatin Effect on HDL Rosuvastatin Effect on LDL –Studies 8, 33 and 65 Comparison of Rosuvastatin and Atorvastatin –Studies 33 and 65 Rosuvastatin Effect on HDL

3. 3 Three Dose Response Studies Type IIa/IIb Patients Study Doses Sample Size Baseline LDL per arm 8 ROSU 1-40 14-18 ~190 33 ROSU 5-80 38-45 ~191 ATOR 10-80 65 ROSU 10-80 158-163 ~189 ATOR 10-80 Study Doses Sample Size Baseline LDL per arm 8 ROSU 1-40 14-18 ~190 33 ROSU 5-80 38-45 ~191 ATOR 10-80 65 ROSU 10-80 158-163 ~189 ATOR 10-80

4. 4 LDL Mean % Change from Baseline for the Dose Range of Rosuvastatin

5. 5 Comparability of Rosuvastatin and Atorvastatin Rosuvastatin is significantly more potent on mg per mg basis What doses are comparable? –2x? 4x? Treatment difference and 95% CI Rosuvastatin is significantly more potent on mg per mg basis What doses are comparable? –2x? 4x? Treatment difference and 95% CI

6. 6 Rosuvastatin vs. 2x Atorvastatin Studies 33 + 65 - LDL % change from baseline Treatment Differences and 95% CI

7. 7 Rosuvastatin 40 vs. Atorvastatin 80 Study 65 - LDL % Change from Baseline LOCF

8. 8 Rosuvastatin vs. 4x Atorvastatin Studies 33 + 65 - LDL % change from baseline Mean Treatment Differences and 95% CI

9. 9 HDL % Change from Baseline Rosuvastatin Compared to Placebo Study BSL 0 5 10 20 40 80 8 ~50 +3% +13% +14% +8% +9% 23 ~55 +3% +11% +15% 24 ~49 +4% +12% +12% 35 ~35 -2% +4% +6% +18% +15% +10% Treatment group n<30 in Studies 8, 23 and 35; ~128 in Study 24 Study BSL 0 5 10 20 40 80 8 ~50 +3% +13% +14% +8% +9% 23 ~55 +3% +11% +15% 24 ~49 +4% +12% +12% 35 ~35 -2% +4% +6% +18% +15% +10% Treatment group n<30 in Studies 8, 23 and 35; ~128 in Study 24

10. 10 HDL % Change from Baseline for Atorvastatin and Rosuvastatin Study 65 Type IIa/IIb

11. 11 SummarySummary Rosuvastatin achieves about 4% more mean LDL-lowering than 2 times the dose of atorvastatin The HDL effects are variable –No dose response relationship Small increase for 20 mg over 10 mg –Consistent with the statin class Rosuvastatin achieves about 4% more mean LDL-lowering than 2 times the dose of atorvastatin The HDL effects are variable –No dose response relationship Small increase for 20 mg over 10 mg –Consistent with the statin class