New Analysis Showed VYTORIN® Superior to Lipitor® in Achieving Lower Levels of LDL Cholesterol, Apolipoprotein B and C-Reactive Protein

Business Wire, March 13, 2006

ATLANTA -- Results from a new post-hoc analysis of the previously presented VYtorin Versus Atorvastatin (VYVA) study of 1,902 patients with high cholesterol showed that a significantly greater number of patients taking VYTORIN(R) (ezetimibe/simvastatin) achieved levels of LDL ("bad") cholesterol of less than 70 mg/dl and Apolipoprotein B(1) (Apo B) levels of less than 90 mg/dL compared with patients taking Lipitor(R) pooled across the dosing range (p<0.001). The analysis also showed that a significantly greater number of patients taking VYTORIN reached levels of LDL cholesterol less than 70 mg/dL and C-Reactive Protein (CRP) levels less than 2 mg/L, compared with patients taking Lipitor pooled across the dosing range (p<0.001). This new analysis was presented today at the American College of Cardiology's 55th Annual Scientific Session.

VYTORIN is indicated as adjunctive therapy to diet for the reduction of elevated total cholesterol, LDL cholesterol, Apo B, triglycerides and non-HDL cholesterol and to increase HDL cholesterol in patients with primary (heterozygous familial and non-familial) hypercholesterolemia or mixed hyperlipidemia. The active ingredients in VYTORIN are ezetimibe and simvastatin. VYTORIN is a prescription medicine and should not be taken by people who are hypersensitive to any of its components. VYTORIN should not be taken by anyone with active liver disease or unexplained persistent elevations of serum transaminases. Women who are of childbearing age (unless highly unlikely to conceive), are nursing or who are pregnant should not take VYTORIN.

High LDL ("bad") cholesterol is widely regarded as a major risk factor for the development of cardiovascular disease (CVD) with a causal relationship to atherosclerosis. Apolipoprotein B is also a well-recognized marker of cardiovascular risk (reflecting levels of LDL together with other atherogenic lipoproteins). According to the American Heart Association (AHA) CRP, a marker of inflammation, is considered an emerging risk factor for cardiovascular disease.(i) Studies of CRP have demonstrated that higher levels are associated with a higher risk for developing coronary events.(ii) The specific relationship between reductions in CRP and/or Apo B in the reduction of CVD risk has not been established. In addition, no drugs including VYTORIN are approved for use in reducing CRP.

"This post hoc analysis showed that VYTORIN was not only significantly better than Lipitor in helping patients achieve an LDL cholesterol of less than 70 mg/dL but significantly more of the patients taking VYTORIN also achieved lower levels of Apo B or CRP than those taking Lipitor," said Christie Ballantyne, M.D., director of the Center for Cardiovascular Disease Prevention, Methodist DeBakey Heart Center, Houston, TX, and lead investigator of the study. "This analysis is interesting; however the clinical significance of these comparisons has not been established and additional studies will be needed to confirm these findings," said Dr. Ballantyne. The NCEP ATP III update does include optional LDL cholesterol of less than 70 mg/dL for very high risk patients and does not include treatment targets for Apo B or CRP.

Overall results from the analysis pooled across the dose range, showed that 32.5 percent of the patients taking VYTORIN (n=891) achieved both levels of LDL cholesterol of less than 70 mg/dL as well as Apo B levels of less than 90 mg/dL as compared to 16 percent of patients taking Lipitor (n=899) across the dosing range. As for patients achieving an LDL cholesterol level of less than 70 mg/dL and a CRP level of less than 2 mg/L, 20.7 percent of the patients taking VYTORIN (n=915) achieved this as compared to 9.8 percent of patients taking Lipitor (n=917; p<0.001) across the dosing range. Mean baseline LDL cholesterol for VYTORIN and Lipitor were 178 mg/dL and 179. mg/dL. The mean baseline Apo B levels were 165 mg/dL in each group and the median baseline CRP was 2.3 mg/L for VYTORIN and 2.5 mg/L for Lipitor.

Study showed VYTORIN was well tolerated

Both VYTORIN and Lipitor were well tolerated in the study. The percentage of patients with clinical and laboratory adverse experiences was generally similar between the two treatment groups.

More on VYVA study

The VYVA study was a multi-center, double-blind, randomized, active-controlled, 8-arm, parallel-group study (6 weeks of active treatment) of 1,902 patients designed to evaluate the efficacy and safety of VYTORIN as compared to Lipitor across their respective dosing ranges in patients with hypercholesterolemia who had not met their LDL cholesterol goal as defined by NCEP ATP III. Mean pooled baseline LDL cholesterol values for VYTORIN and Lipitor were 178 mg/dL and 179 mg/dL, respectively. Mean baseline LDL cholesterol values for VYTORIN and Lipitor were comparable at each dose comparison.

VYTORIN lowered LDL cholesterol by 53 percent across the dosing range as compared to 45 percent lowering seen in those patients taking Lipitor across the dosing range. At the most commonly used starting doses, patients taking VYTORIN 10/20 mg/dL reduced their LDL cholesterol by 51 percent as compared to the 36 percent reduction seen in patients taking Lipitor 10 mg (p<0.001).