1. Slide 1 EZT 2002-W-6022-SS Ezetimibe Co-administered with Statins: Efficacy and Tolerability Copyright © 2003 MSP Singapore Company, LLC. All rights reserved.

2. Slide 2 EZT 2002-W-6022-SS Ezetimibe Together with Statins Co-administration Studies Ezetimibe 10 mg co-administered with a statin in eight randomized phase III clinical trials Double-blind placebo-controlled studies –Co-administration at start of therapy (lovastatin, simvastatin, pravastatin, atorvastatin) –Addition to current statin in patients with CHD or multiple cardiovascular risk factors –Addition to therapy in patients not controlled by atorvastatin 10 mg or simvastatin 20 mg Double-blind study –Addition to statin in patients with HoFH Statins administered across the full range of recommended doses Doses administered once daily CHD = coronary heart disease; HoFH = homozygous familial hypercholesterolemia

3. Slide 3 EZT 2002-W-6022-SS Initial Co-administration Study Design *Only atorvastatin and simvastatin were given in an 80 mg dose. Placebo Ezetimibe 10 mg StatinStatinStatinStatin Placebo 10 mg20 mg40 mg80 mg* Statins: atorvastatin*, simvastatin*, lovastatin, and pravastatin >2300 patients; 65 patients per group Primary endpoint: % reduction from baseline in LDL-C –Statin alone vs. ezetimibe + statin –Pairwise comparisons between treatment groups

4. Slide 4 EZT 2002-W-6022-SS Ezetimibe Co-administered with Statins: LDL-C Efficacy *p<0.01 ezetimibe + pooled statin doses vs. pooled statin doses alone Ezetimibe 10 mg + pooled atorvastatin (n=255) Pooled atorvastatin (n=248) Ezetimibe 10 mg + pooled simvastatin (n=274) Pooled simvastatin (n=263) Ezetimibe 10 mg + pooled lovastatin (n=192) Pooled lovastatin (n=220) Ezetimibe 10 mg + pooled pravastatin (n=204) Pooled pravastatin (n=205) –50 –40 –30 –20 –10 0 –60 –56.3 –44.2 12.1%* 14.8%* –51.3 –36.5 15.0%* –40.4 –25.4 13.4%* –38.6 –25.2 Mean % change in calculated LDL-C from baseline at 12 weeks

5. Slide 5 EZT 2002-W-6022-SS Ezetimibe Co-administered with Simvastatin: LDL-C Efficacy *p<0.01 combination therapy vs. statin alone –46 –45 –27* –36* –38* Mean % change in calculated LDL-C from baseline at 12 weeks 10 mg Ezetimibe 10 mg + simvastatin 10 mg 80 mg40 mg20 mg Simvastatin –50 –40 –30 –20 –10 0 –60

6. Slide 6 EZT 2002-W-6022-SS Ezetimibe Co-administered with Atorvastatin: LDL-C Efficacy *p<0.01 combination therapy vs. statin alone 10 mg Ezetimibe 10 mg + atorvastatin 10 mg 80 mg40 mg20 mg Atorvastatin –50 –40 –30 –20 –10 0 –60 – 54 – 45* – 42* – 37* – 53 Mean % change in calculated LDL-C from baseline at 12 weeks

7. Slide 7 EZT 2002-W-6022-SS *p  0.01 ezetimibe + pooled statin doses vs. pooled statin doses alone Ezetimibe Co-administered with Statins: TG Efficacy –30 –20 –10 0 –40 –33 –24 –29 –20 –25 –12 –21 –14 9%* 13%* 7%* Mean % change in TG from baseline at 12 weeks Ezetimibe 10 mg + pooled atorvastatin (n=255) Pooled atorvastatin (n=248) Ezetimibe 10 mg + pooled simvastatin (n=274) Pooled simvastatin (n=263) Ezetimibe 10 mg + pooled lovastatin (n=192) Pooled lovastatin (n=220) Ezetimibe 10 mg + pooled pravastatin (n=204) Pooled pravastatin (n=205)

8. Slide 8 EZT 2002-W-6022-SS *p  0.05 ezetimibe + pooled statin doses vs. pooled statin doses alone Ezetimibe Co-administered with Statins: HDL-C Efficacy Mean % change in HDL-C from baseline at 12 weeks 2 4 6 8 10 0 7 9 7 9 4 8 7 4 3%* 2%* 5%* 1% Ezetimibe 10 mg + pooled atorvastatin (n=255) Pooled atorvastatin (n=248) Ezetimibe 10 mg + pooled simvastatin (n=274) Pooled simvastatin (n=263) Ezetimibe 10 mg + pooled lovastatin (n=192) Pooled lovastatin (n=220) Ezetimibe 10 mg + pooled pravastatin (n=204) Pooled pravastatin (n=205)

9. Slide 9 EZT 2002-W-6022-SS Ezetimibe Co-administered with Statins versus High-Dose Statins Ezetimibe 10 mg once daily together with the lowest statin dose reduced plasma LDL-C as much as or more than the highest dose tested of statin alone. Mean % change in LDL-C from baseline –40 –20 0 –60 Atorvastatin 80 mg (n=62) –54 Ezetimibe 10 mg + atorvastatin 10 mg (n=65) –53 Simvastatin 80 mg (n=66) –45 Ezetimibe 10 mg + simvastatin 10 mg (n=67) –46 Lovastatin 40 mg (n=73) –30 Ezetimibe 10 mg + lovastatin 10 mg (n=64) –34 Pravastatin 40 mg (n=69) –31 Ezetimibe 10 mg + pravastatin 10 mg (n=71) –34

10. Slide 10 EZT 2002-W-6022-SS Ezetimibe Co-administered with Statins: Easier Control of LDL-C One-step co-administration of ezetimibe equivalent to three-step statin titration Adapted from Stein E Eur Heart J Suppl 2001;3(suppl E):E11-E16. 060 Three-step titration One-step co-administration Statin 10 mg + Ezetimibe 10 mg 5040302010 20 mg 40 mg 80 mg % reduction in LDL-C

11. Slide 11 EZT 2002-W-6022-SS Ezetimibe Co-administration with Ongoing Statin Study Objectives Adapted from Gagné C et al Am J Cardiol 2002;90:1084-1091. Assess efficacy and safety profile of ezetimibe 10 mg/day co-administered with ongoing statin monotherapy in patients needing further LDL-C lowering Primary endpoint –LDL-C–lowering efficacy of co-administering ezetimibe 10 mg/day vs. placebo with a statin Secondary endpoints –TG-lowering and HDL-C–increasing efficacy –Patients achieving target LDL-C values with ezetimibe vs. placebo –Tolerability

12. Slide 12 EZT 2002-W-6022-SS Ezetimibe Co-administration with Ongoing Statin Study Design *21 patients in the placebo group and 23 patients in the ezetimibe group were enrolled while taking nonmarketed doses of statins. Adapted from Gagné C et al Am J Cardiol 2002;90:1084-1091. Screening Co-administration phase (ezetimibe or placebo with statin)* Simvastatin(n=240) Atorvastatin(n=308) Other statins (n=221) Randomize Ezetimibe 10 mg (n=114) Placebo (n=112) Patients taking statin who require further LDL-C lowering Ezetimibe 10 mg (n=136) Placebo (n=152) Ezetimibe 10 mg (n=106) Placebo (n=105)

13. Slide 13 EZT 2002-W-6022-SS Ezetimibe Co-administered with Ongoing Statin Therapy: Effect on Lipid Levels *p<0.001 vs. statin + placebo **p<0.05 vs. statin + placebo ***median % change Adapted from Gagné C et al Am J Cardiol 2002;90:1084-1091. – 25* – 14* –4–4 –3–3 1 3** –30 –25 –20 –15 –10 –5–5 0 5 Mean % change from baseline at 8 weeks Mean % change from baseline at 8 weeks –11% –21% Statin and placebo (n=390) Statin and ezetimibe (n=379) LDL-C HDL-C TG***

14. Slide 14 EZT 2002-W-6022-SS Ezetimibe Co-administered with Ongoing Statin Therapy: Better LDL-C Goal Attainment *p<0.001 vs. statin monotherapy **p<0.01 vs. statin monotherapy NCEP ATP = National Cholesterol Education Program Adult Treatment Panel Adapted from Gagné C et al Am J Cardiol 2002;90:1084-1091. Statin monotherapy (n=388) Ezetimibe + statin (n=375) % of patients at LDL-C goal at 8 weeks All patientsPatients not above goal at baseline 20 40 60 0 80 100 76* 27 72* 19 NCEP ATP II Goal Attainment

15. Slide 15 EZT 2002-W-6022-SS Ezetimibe Co-administered with Ongoing Statin Therapy: Consistent LDL-C Reductions Across Patient Subgroups BMI = body mass index Adapted from Gagné C et al Am J Cardiol 2002;90:1084-1091. Placebo + statin Ezetimibe 10 mg + statin Difference between treatments Mean difference in % LDL-C reduction between treatments % LDL-C reduction by treatment group Non-Caucasian Caucasian  65 years <65 years WomenMen 2 4 6 8 10 12 14 16 18 20 22 24 26 28 30 2 4 6 8 10 12 14 16 18 20 22 24 26 28 30 10 15 20 25 30 Similar consistency observed for NCEP ATP II risk grades and BMI subcategories

16. Slide 16 EZT 2002-W-6022-SS Ezetimibe Co-administered with Statins: Consistency of Study Results Ezetimibe plus statin resulted in 20 to 22% lower LDL-C than statin alone Mean LDL-C (mmol/L) at study end 0.5 1.5 2.5 3.0 3.5 0 1.0 2.0 Statin alone Statin + ezetimibe Atorvastatin 2.1 2.7 22% Simvastatin 2.3 2.9 21% Pravastatin 2.8 3.5 20% Lovastatin 2.8 3.5 20% Ongoing statins 2.7 3.4 21% 0.5 1.5 2.5 3.0 3.5 0 1.0 2.0

17. Slide 17 EZT 2002-W-6022-SS Ezetimibe Co-administration with a Statin for Treatment of HoFH *p=0.007 vs. statin alone **p=0.0001 vs. statin alone Adapted from Gagné C et al Circulation 2002;105:2469-2475. % LDL-C reduction at 12 weeks –20 –10 0 –30 Statin 80 mg (n=17) Ezetimibe + statin 40 or 80 mg (n=33) –20.7% * –6.7% –27.5% ** –7.0% Statin 80 mg (n=17) Ezetimibe + statin 80 mg (n=17)

18. Slide 18 EZT 2002-W-6022-SS Data from Controlled Clinical Trials: Ezetimibe Tolerability and Safety Profile in Co-administration Tolerability profile of ezetimibe + statin similar to that of statin alone Tolerability profile of ezetimibe monotherapy similar to that of placebo No increased risk of hematologic or blood chemistry abnormalities over statin alone No clinically significant ezetimibe–statin pharmacokinetic interactions Ezetimibe PlaceboEzetimibeStatin+ statin (n=259)(n=262)(n=936)(n=925) Treatment-related AE (%)18.115.616.919.5 Discontinuation due to 3.9 2.7 2.5 3.7 treatment-related AE (%) Serious treatment-related AE (%)0 0.4 0.1 1.1

19. Slide 19 EZT 2002-W-6022-SS Ezetimibe Initial Co-administration with Statin Studies: Pooled Safety Data *From placebo-controlled monotherapy studies **All asymptomatic and reversible with drug continuation or discontinuation GI = gastrointestinal; ULN = upper limit of normal; ALT = alanine aminotransferase; AST = aspartate aminotransferase; GGT = gamma-glutanyl transpepsidase; CK = creatine kinase Adapted from Melani L et al. Presented at American Diabetes Association Meeting, San Francisco, CA, July 14–18, 2002. Ezetimibe Ezetimibe Statin + statin Placebo* 10 mg(pooled) (pooled) (n=259) (n=262) (n=936) (n=925) Adverse events, no. (%)166 (64.1) 177 (67.6)606 (64.7)593 (64.1) GI disorders, no. (%) 47 (18.1) 54 (20.6)171 (18.3)155 (16.8) Liver function tests (  3  ULN)** ALT, no. (%)—total 0 (0) 0 (0) 4 (0.4) 12 (1.3) AST, no. (%) 0 (0) 0 (0) 3 (0.3) 5 (0.5) GGT, no. (%) 3 (1.2) 9 (3.5) 26 (2.8) 33 (3.6) CK (  10  ULN), no. (%) 0 (0) 0 (0) 4 (0.4) 1 (0.1) Myalgia, no. (%) 12 (4.6) 13 (5.0) 38 (4.1) 42 (4.5)

20. Slide 20 EZT 2002-W-6022-SS Initial Co-administration of Ezetimibe with Statins: Summary Phase III trials of ezetimibe + statin show –Additive effects of ezetimibe + atorvastatin, simvastatin, pravastatin, or lovastatin on LDL-C reduction –LDL-C–lowering efficacy of ezetimibe + lowest-dose statin comparable to maximum dose of every statin tested –Beneficial effects on HDL-C and TG –Good tolerability

21. Slide 21 EZT 2002-W-6022-SS Ezetimibe Co-administration with Ongoing Statin Therapy: Summary Significant additional efficacy –LDL-C lowered 21% more than placebo (p<0.001) –HDL-C raised 2% more than placebo (p<0.05) –TG lowered 11% more than placebo (p<0.001) Significantly better NCEP ATP II goal attainment among patients not at goal when randomized (p<0.001) –72% (vs. 19%, statin + placebo) Adapted from Gagné C et al Am J Cardiol 2002;90:1084-1091.

22. Slide 22 EZT 2002-W-6022-SS Ezetimibe: Dosage and Administration Recommended dose of ezetimibe is 10 mg once daily, co- administered with a statin or alone, to be used as per approved product information Ezetimibe may be taken at any time of day, with or without food Ezetimibe is not recommended for patients with moderate or severe hepatic insufficiency Ezetimibe co-administration with fibrates has not been studied and is not recommended No important interactions with commonly used drugs (cholestyramine lowered mean AUC of ezetimibe by 55%) AUC = area under the plasma concentration-time curve

23. Slide 23 EZT 2002-W-6022-SS Before prescribing, please consult full manufacturer’s prescribing information.