CE-1 CRESTOR ® Clinical Development Efficacy James W. Blasetto, MD, MPH Senior Director, Clinical Research

CE-2 Evolution of Lipid Management Guidelines: The National Cholesterol Education Program (NCEP) Adult Treatment Panel (ATP) Exclusive focus on LDL-C reduction Strong support for resins, niacin Statins, fibrates not first line ATP I (1988) Risk assessment guides therapy Goal LDL-C for CHD set at ≤ 100 mg/dL Statins included in "major drugs" ATP II (1993) Identifies optimal LDL-C level < 100 mg/dL High-risk patient group now includes patients with CHD risk equivalent, LDL-C goal < 100 mg/dL Increased focus on HDL-C; non-HDL-C as a secondary target of therapy ATP III (2001)

CE-3 Many Patients With CHD Fail to Achieve LDL-C and Non-HDL-C Goals Even With Dose Titration ACCESS †Patients in CHD risk category. Ballantyne CM, et al. Am J Cardiol. 2001;88: n = 2,543 † At Wk 54

CE-4 Provide an overall benefit-risk profile demonstrating –Greater beneficial effects on key lipid parameters at both the start dose and across the dose range compared with marketed statins –A similar safety profile compared with approved drugs in the statin class –A low potential for significant drug-drug interactions Objectives of the Rosuvastatin Clinical Development Program

CE-5 Efficacy in LDL-C Reduction Dose-Range Effects

CE-6 LDL-C: % Change From Baseline Rosuvastatin vs Placebo Trials 8 and 23 Pooled (Wk 6) P <.001 vs placebo; data presented as LS mean ± SE Placebo n = Baseline characteristics Mean age: 56 yr Mean LDL-C: 190 mg/dL

CE-7 Lipids: % Change From Baseline Rosuvastatin 5 mg and 10 mg Trials Pooled (Wk 12) Data presented as means ± SE. Baseline characteristics Mean age: 58 yr Mean LDL-C: 187 mg/dL

CE-8 LDL-C: % Change From Baseline Rosuvastatin 20 mg and 40 mg Multiple Trials 8 Trial N1718 Data presented as LS means.

CE-9 Across the Dose-Range Comparative Efficacy

CE-10 6-wk dietary lead-in 6-wk active treatment Randomization Rosuvastatin (643 patients) 10 mg 20 mg 40 mg 10 mg 20 mg 40 mg 80 mg 10 mg 20 mg 40 mg 10 mg 20 mg 40 mg Simvastatin (655 patients) Atorvastatin (641 patients) Pravastatin (492 patients) 80 mg Across the Dose-Range Comparison Trial Design Trial 65 – STELLAR Baseline characteristics Mean age: 57 yr Mean LDL-C: 189 mg/dL

CE-11 LDL-C: % Change From Baseline Rosuvastatin 10 to 40 mg vs Comparators Trial 65 – STELLAR (Wk 6) P <.001 vs comparators on a mg-to-mg basis. Data presented as means.

CE Rosuva, mg % change from baseline LDL-C: % Change From Baseline Rosuvastatin 10 to 40 mg vs Comparators Trial 65 – STELLAR (Wk 6) Atorva, mg N = Simva, mg Prava, mg

CE-13 HDL-C: % Change From Baseline Rosuvastatin 10 to 40 mg vs Comparators Trial 65 – STELLAR (Wk 6) P <.002 RSV 10 mg vs PRA 10 mg. P <.002 RSV 20 mg vs ATV 20 mg, 40 mg, 80 mg; PRA 20 mg, 40 mg; SIM 40 mg. P <.002 RSV 40 mg vs ATV 40 mg, 80 mg; PRA 40 mg; SIM 40 mg. Data presented as LS means ± SE. N =

CE-14 Non HDL-C: % Change From Baseline Rosuvastatin 10 to 40 mg vs Comparators Trial 65 – STELLAR (Wk 6) P <.002 RSV 10 mg vs ATV 10 mg; PRA 10 to 40 mg; SIM 10 to 40 mg. P <.002 RSV 20 mg vs ATV 20 mg; PRA 20 mg, 40 mg; SIM 20 to 80 mg. P <.002 RSV 40 mg vs ATV 40 mg; PRA 40 mg; SIM 40 mg, 80 mg. Data presented as LS means ± SE. N=

CE-15 Efficacy in Achievement of NCEP Targets Trial 26 Titration to Goal Comparison to Atorvastatin

CE-16 Rosuva 5 mg Rosuva 10 mg 10 mg 20 mg 40 mg 80 mg 40 mg 80 mg 20 mg 40 mg 80 mg Atorva 10 mg Titration to Goal Comparison With Atorvastatin: Titration Scheme Trial 26 Baseline characteristics Mean age: 57 yr Mean LDL-C: 187 mg/dL 6-wk dietary lead-in 52-wk active treatment Titrated to goals if needed after wk 12 Randomization Titration phase n = 138 n = 134 n = 140

CE-17 % Achieving ATP II LDL-C Goal Rosuvastatin 10 to 40 mg vs Atorvastatin 10 to 80 mg Trial 26 (Wk 52) Rosuvastatin n = 106 Atorvastatin n = 116 Patients, % *P <.05 vs atorvastatin. Reached on 10 mg 82% 59% Reached on 80 mg Reached on 40 mg Reached on 20 mg * 96% 87%

CE-18 Efficacy in Patients With Severe Hypercholesterolemia: Comparison With Atorvastatin Trial 30 Patients With Heterozygous Familial Hypercholesterolemia (FH)

CE-19 Heterozygous Familial Hypercholesterolemia Rosuvastatin vs Atorvastatin—Trial Design Trial 30 Forced-titration Baseline characteristics Mean age: 48 yr Mean LDL-C: 291 mg/dL RSV 20 mg n = 435 ATV 20 mg n = mg80 mg 40 mg80 mg 6-wk dietary lead-in 18-wk active treatment Titrated at Wk 6, 12, and 18

CE-20 LDL-C: % Change From Baseline Rosuvastatin vs Atorvastatin: Heterozygous FH Trial 30 (Wk ) * * *P <.05 vs atorvastatin; data presented as LS means ± SE. * 20 mg40 mg 80 mg

CE-21 HDL-C: % Change From Baseline Rosuvastatin vs Atorvastatin: Heterozygous FH Trial 30 (Wk ) *P <.05 vs atorvastatin; data presented as LS means ± SE. * * * 20 mg40 mg80 mg

CE-22 % Achieving ATP III LDL-C Goal—All Categories Rosuvastatin vs Atorvastatin: Heterozygous FH Trial 30 (Wk ) *P <.05 vs atorvastatin. * * * 20 mg40 mg80 mg

CE-23 % Achieving ATP III LDL-C Goal—High Risk Rosuvastatin vs Atorvastatin: Heterozygous FH Trial 30 (Wk ) *P <.05 vs atorvastatin; high-risk patients with atherosclerosis/diabetes. * LDL-C goal < 100 mg/dL * 20 mg40 mg80 mg

CE-24 Summary of Efficacy Rosuvastatin 10 mg to 40 mg reduced LDL-C 50% to 62% Rosuvastatin lowered LDL-C and non-HDL-C more than atorvastatin, simvastatin, and pravastastin across the dose range –Greater increases in HDL-C observed More patients achieved NCEP goals with a rosuvastatin regimen (10 to 40 mg), than with atorvastatin (10 to 80 mg), simvastatin (20 to 80 mg), or pravastatin (20 to 40 mg)