Merck/Schering-Plough Pharmaceuticals, a joint venture between Merck & Co Inc and Schering-Plough Corporation, announced that the US Food and Drug Administration has approved Vytorin (ezetimibe/simvastatin) for the treatment 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 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 are ezetimibe and simvastatin. The recommended starting dose of Vytorin is 10/20 mg (10 mg ezetimibe/20 mg simvastatin), a release from Merck says.

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

"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, director of the Centre for Cardiovascular Disease Prevention, Methodist DeBakey Heart Center, Houston, TX.

In a 24-week, multi-centre, randomized, double-blind, active-controlled, forced titration study of 788 patients, Vytorin (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 treatment groups ranged from 179 mg/dl to 181 mg/dl. At each pre-specified dose comparison, Vytorin lowered LDL cholesterol to a significantly greater degree than atorvastatin. At the recommended usual starting doses, Vytorin 10/20 mg lowered LDL cholesterol by 50 per cent vs. 37 per cent for atorvastatin 10 mg and 44 per cent for atorvastatin 20 mg. The impact on clinical outcomes of these differences in lipid altering effects is unknown, the release says.

"Vytorin is the first single cholesterol treatment to provide LDL cholesterol lowering through dual inhibition of cholesterol production and absorption. Vytorin represents an important new treatment alternative for the millions of patients 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," Fred added.

"The dual inhibition of cholesterol provided by Vytorin delivers impressive LDL cholesterol reductions across the dosing range and offers physicians a unique and powerful new option in the evolving treatment of hyperlipidemia, especially in people who need more aggressive treatment to reach goal," said Margo Denke, clinical professor, University of Texas Health Science Centre, San Antonio, TX.

Results from a phase III, multi-centre, randomized, double-blind controlled study of 710 patients showed that, after five weeks of treatment, Vytorin 10/20 mg lowered LDL cholesterol by 53 per cent compared to a 38 per cent reduction with simvastatin 20 mg. This greater LDL cholesterol reduction resulted in 83 per cent of patients treated with Vytorin 10/20 mg achieving the study LDL cholesterol goal of less than 100 mg/dL as compared to 46 per cent of patients taking simvastatin 20 mg.

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, the release added.

Merck/Schering-Plough Pharmaceuticals is formed to develop and market in the United States new prescription medicines in cholesterol management.