FDA Approves Vytorin

Vytorin Merck/Schering-Plough Pharmaceuticals - Treatment for Cholesterol Reduction

WHITEHOUSE STATION and KENILWORTH, NJ -- July 26, 2004 -- Merck and Schering-Plough Pharmaceuticals announced that the U.S. Food and Drug Administration has approved Vytorin™ (ezetimibe/simvastatin) for the treaent of high LDL cholesterol (LDL-C) in patients with primary hypercholesterolemia or mixed hyperlipidemia as adjunctive therapy to diet when diet alone is not enough. Vytorin, which is also marketed as Inegy™ in Germany, is the first and only product approved to treat the two sources of cholesterol by inhibiting the production of cholesterol in the liver and blocking the absorption of cholesterol in the intestine, including cholesterol from food. The active ingredients in Vytorin (Inegy) are ezetimibe and simvastatin. The recommended starting dose of Vytorin in the United States is 10/20 mg (10 mg ezetimibe/20 mg simvastatin).

"Many patients who continue to have high cholesterol despite diet and other lifestyle modifications may require powerful LDL cholesterol lowering agents and to do this we frequently look to highly efficacious medicines to provide the reduction they need," said Christie Ballantyne, M.D., director of the Center for Cardiovascular Disease Prevention, Methodist DeBakey Heart Center, Houston, Texas, U.S.A.

Vytorin (Inegy) lowered LDL cholesterol by 52 percent at the recommended starting dose (10/20 mg) and 60 percent at the maximum dose (10/80 mg)

In a 12-week, multi-center, double-blind, placebo-controlled clinical study of 1,528 patients with LDL cholesterol levels of 145 mg/dL to 250 mg/dL, Vytorin (Inegy) provided LDL cholesterol reductions of 52 percent at the recommended starting dose (10/20 mg), 55 percent at the 10/40 mg dose and 60 percent at the maximum dose (10/80 mg). Vytorin (Inegy) is administered as a once-daily tablet and should be taken in the evening with or without food.

"Vytorin is the first single cholesterol treaent to provide LDL cholesterol lowering through dual inhibition of cholesterol production and absorption. Vytorin represents an important new treaent alternative for the millions of patients in the United States with elevated cholesterol for whom diet alone is not enough," said Raymond V. Gilmartin, chairman, president, and chief executive officer of Merck & Co., Inc. "With the approval of Vytorin, physicians have a powerful new option that treats the two sources of cholesterol in one tablet," said Fred Hassan, chairman and chief executive officer of Schering-Plough. "Vytorin represents an important new therapy that can provide patients with significant LDL cholesterol reductions."

In head-to-head trials, Vytorin (Inegy) provided greater reductions in LDL cholesterol than atorvastatin (Lipitor®) and simvastatin (Zocor®) across the dosing range

In a 24-week, multi-center, randomized, double-blind, active-controlled, forced titration study of 788 patients, Vytorin (Inegy, doses ranging from 10/10 mg to 10/80 mg) was compared to atorvastatin monotherapy (doses ranging from 10 mg to 80 mg). The average LDL cholesterol levels at baseline across treaent groups ranged from 179 mg/dL to 181 mg/dL. At each pre-specified dose comparison Vytorin (Inegy) lowered LDL cholesterol to a significantly greater degree than atorvastatin. At the recommended usual starting doses, Vytorin (Inegy) 10/20 mg lowered LDL cholesterol by 50 percent vs. 37 percent for atorvastatin 10 mg and 44 percent for atorvastatin 20 mg. The impact on clinical outcomes of these differences in lipid altering effects is unknown.

In the 12-week study of 1,528 patients with LDL cholesterol levels of 145 mg/dL to 250 mg/dL, those taking Vytorin (Inegy) experienced significantly greater LDL cholesterol reductions compared to simvastatin. Vytorin (Inegy) 10/20 mg achieved a 52 percent LDL cholesterol reduction compared to reductions of 34 percent and 41 percent, respectively, for simvastatin 20 mg and 40 mg (typical starting doses for simvastatin). No incremental benefit of Vytorin (Inegy) on cardiovascular morbidity and mortality over and above that demonstrated for simvastatin has been established.

In a clinical trial, greater LDL cholesterol reduction with Vytorin (Inegy) compared to simvastatin (Zocor) resulted in greater goal attainment

Results from a phase III, multi-center, randomized, double-blind, controlled study of 710 patients showed that after five weeks of treaent, Vytorin (Inegy) 10/20 mg lowered LDL cholesterol by 53 percent compared to a 38 percent reduction with simvastatin 20 mg. This greater LDL cholesterol reduction resulted in 83 percent of patients treated with Vytorin 10/20 mg achieving the National Cholesterol Education Program/Adult Treaent Panel (NCEP/ATP) III [i] LDL cholesterol goal of less than 100 mg/dL as compared to 46 percent of patients taking simvastatin 20 mg.

Patients in this study were randomized to one of four treaent groups for 23 weeks: Vytorin (Inegy, 10/10 mg, 10/20 mg, or 10/40 mg) or simvastatin 20 mg. All 710 patients enrolled in the study had LDL cholesterol levels of 130 mg/dL or more (mean 165 mg/dl to 174 mg/dl across treaent arms) and coronary heart disease (CHD) or CHD risk equivalents as defined by NCEP ATP III Guidelines.

Vytorin (Inegy) lowers cholesterol through dual inhibition of cholesterol production by the body and absorption in the small intestine

Cholesterol in the blood is derived from two sources - production by the body and absorption from the small intestine. The most widely prescribed cholesterol lowering medications, called statins, work in the liver to reduce cholesterol production and increase clearance of cholesterol from the bloodstream. Vytorin inhibits absorption of cholesterol in the small intestine, while also reducing cholesterol synthesis in the liver leading to clearance of cholesterol from the bloodstream.

Posted: July 2004

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Vytorin (ezetimibe/simvastatin) FDA Approval History

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