1. Downloaded from www.ezetrol.aewww.ezetrol.ae Slide 1 Dual Inhibition of Two Sources of Cholesterol: Absorption and Production Results of a Clinical Trial with Ezetimibe Coadministered with Simvastatin

2. Downloaded from www.ezetrol.aewww.ezetrol.ae Slide 2 Ezetimibe Coadministered with Simvastatin* Efficacy Factorial Study Design –Multicenter, double-blind, randomized, placebo-controlled, factorial design, 12-week study Treatment groups –Ezetimibe + Simvastatin 10–80 mg once daily (n=353) –Simvastatin 10–80 mg once daily (n=349) –Ezetimibe 10 mg once daily (n=92) –Placebo (n=93) Selected entry criteria –Age  18 years –LDL-C 145–250 mg/dl (3.7–6.4 mmol/L) –Triglycerides ≤350 mg/dl (≤3.96 mmol/L) *Eze+Simva in this presentation. Adapted from Goldberg AC et al. Poster presentation at the 53rd ACC, March 7–10, 2004.

3. Downloaded from www.ezetrol.aewww.ezetrol.ae Slide 3 Endpoints Primary –Percent change from baseline in plasma LDL-C Key secondary –Percentage of patients reaching target LDL-C levels (<100 mg/dl) –Percent change from baseline in other lipid and inflammatory parameters Adapted from Goldberg AC et al. Poster presentation at the 53rd ACC, March 7–10, 2004.

4. Downloaded from www.ezetrol.aewww.ezetrol.ae Slide 4 Baseline Characteristics Eze+ Simva 10–80 mg (n=340–353) Simvastatin 10–80 mg (n=328–349) Ezetimibe 10 mg (n=84–92) Placebo (n=88–93) Age (%) <65 years  65 years 75 25 77 23 79 21 71 29 Gender (% of patients) Male Female 48 52 49 51 38 62 41 59 Race (% of patients) White Black Hispanic Other 83 3 9 5 79 4 10 7 77 7 10 7 81 5 9 5 Mean LDL-C (mg/dl)175 176174 Mean total cholesterol (mg/dl)260259262258 Mean HDL-C (mg/dl)51495150 Median triglycerides (mg/dl)169167163162 Adapted from Goldberg AC et al. Poster presentation at the 53rd ACC, March 7–10, 2004.

5. Downloaded from www.ezetrol.aewww.ezetrol.ae Slide 5 LDL-C Reduction Across the Dose Range Mean % change from baseline to week 12 0 –20 –30 –40 –50 –10 –70 –60 Eze+ Simva 10 mg (n=87) –46%* Simva 10 mg (n=79) –31% Eze+ Simva 20 mg (n=86) –51%* Simva 20 mg (n=89) –35% Eze+ Simva 40 mg (n=89) –55%* Simva 40 mg (n=90) –42% Eze+ Simva 80 mg (n=91) –61%* Simva 80 mg (n=87) –46% *p<0.001 vs. corresponding dose of simvastatin Adapted from Goldberg AC et al. Poster presentation at the 53rd ACC, March 7–10, 2004.

6. Downloaded from www.ezetrol.aewww.ezetrol.ae Slide 6 Percentage of Patients Reaching Target LDL-C Goal *Subgroup of patients who were not at goal at baseline **p<0.001 vs. simvastatin Adapted from Goldberg AC et al. Poster presentation at the 53rd ACC, March 7–10, 2004. % Patients* at goal at week 12 100 80 60 40 20 Target LDL-C (<100 mg/dl) 0 Eze+Simva 10–80 mg pooled doses (n=291) Simvastatin 10–80 mg pooled doses (n=148) 43% 82%**

7. Downloaded from www.ezetrol.aewww.ezetrol.ae Slide 7 Changes in Other Lipid Parameters *Except for triglycerides, shown as median percent changes **p<0.001 vs. simvastatin Adapted from Goldberg AC et al. Poster presentation at the 53rd ACC, March 7–10, 2004. Mean* % change from baseline to week 12 0 –20 –40 –60 –26% –38%** Total cholesterolHDL-C +8% Triglycerides –28%** –15% 20 Eze+Simva 10–80 mg pooled doses (n=353) Simvastatin 10–80 mg pooled doses (n=345)

8. Downloaded from www.ezetrol.aewww.ezetrol.ae Slide 8 Changes in Other Cardiovascular Parameters *Except for C-reactive protein (CRP), shown as median percent changes **p<0.001 vs. simvastatin 10–80 mg Adapted from Goldberg AC et al. Poster presentation at the 53rd ACC, March 7–10, 2004. Mean* % change from baseline to week 12 0 –20 –40 –60 –42%** –9% –33%** Apo BCRP –34% –49%** Non–HDL-C Eze+Simva 10–80 mg pooled doses Simvastatin 10–80 mg pooled doses (n=340)(n=328)(n=353)(n=345)(n=209)(n=204) –29%

9. Downloaded from www.ezetrol.aewww.ezetrol.ae Slide 9 LDL-C–Lowering Efficacy Over Time Mean % change from baseline 0 –20 –30 –40 –50 –60 Baseline Eze+Simva 20–80 mg pooled doses (n=539) Simvastatin 20–80 mg pooled doses (n=229) –10 Week 24Week 36Week 48Week 60 Extension study endpoint

10. Downloaded from www.ezetrol.aewww.ezetrol.ae Slide 10 Safety Profile Results Adapted from Goldberg AC et al. Poster presentation at the 53rd ACC, March 7–10, 2004. Number (%) Pooled Eze+ Simva 10–80 mg (n=353) Pooled Simvastatin 10–80 mg (n=349) Ezetimibe 10 mg (n=92) Placebo (n=93) Clinical AE214 (61)219 (63)52 (57)61 (66) Drug-related clinical AE48 (14)46 (13)8 (9) Serious clinical AE3 (<1)4 (1)01 (1) Drug-related serious clinical AE0000 Discontinuation due to any AE16 (5)7 (2)3 (3)2 (2) Discontinuation due to any drug- related AE 13 (4)5 (1)2 (2)0 Consecutive  3  ULN elevation in ALT and/or AST 6 (2)000 CPK  10  ULN 2 (<1)1 (<1)01 (1)

11. Downloaded from www.ezetrol.aewww.ezetrol.ae Slide 11 Conclusions Eze+Simva was significantly more effective (p<0.001) in reducing plasma LDL-C than simvastatin monotherapy through Dual Inhibition of two sources of cholesterol: production and absorption Mean LDL-C reductions approximately 15% greater with Eze+Simva vs. the corresponding dose of simvastatin Greater LDL-C efficacy across the dose range of Eze+Simva vs. simvastatin—61% reduction with Eze+Simva 80 mg Significantly more patients achieved target LDL-C goals with Eze+Simva than with simvastatin alone (p<0.001) Eze+Simva improved the overall lipid profile vs. baseline (total C, apo B, triglycerides, HDL-C, non–HDL-C) and CRP

12. Downloaded from www.ezetrol.aewww.ezetrol.ae Slide 12 References Please refer to notes page.

13. Downloaded from www.ezetrol.aewww.ezetrol.ae Slide 13 Dual Inhibition of Two Sources of Cholesterol: Absorption and Production Before prescribing, please consult the manufacturers’ prescribing information. MSP does not recommend the use of any product in any different manner than as described in the prescribing information. Copyright © 2004 MSP Singapore Company, LLC. All rights reserved.5-05 EZT 2004-W-6132-SS Printed in USA