INEGY™ (ezetimibe/simvastatin) Is Superior To Crestor™ (rosuvastatin) In Reducing LDL Cholesterol

Main Category: Statins
Also Included In: Cholesterol;  Cardiovascular / Cardiology
Article Date: 20 Oct 2006 - 8:00 PDT

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INEGY™ (ezetimibe/simvastatin) provides significantly greater LDL ("bad") cholesterol (LDL-C) reduction compared with rosuvastatin (Crestor™) in patients with primary hypercholesterolemia, according to data published this week in the international journal Current Medical Research and Opinion (CMRO).(1)

The study, which provides the first comparative data for INEGY™ versus rosuvastatin, was performed to assess the efficacy for LDL-C lowering of INEGY™ compared with rosuvastatin at the approved usual and alternate starting doses and maximum doses. At each dose comparison and across doses, INEGY™ reduced LDL-C levels significantly more than rosuvastatin. When averaged across doses, there was a greater reduction in LDL-C from baseline with INEGY compared to rosuvastatin, (-4.2 per cent, p<0.05).(1)

Additional data from the study showed that when treating two sources of cholesterol - that is, inhibiting both cholesterol absorption and production - with INEGY™, a significantly greater percentage of high-risk patients reached their NCEP ATP III goal of LDL-C <100 mg/dL (INEGY = 90.1 per cent versus. rosuvastatin = 82.0 percent, p<0.05 - when pooled across doses). Furthermore, significantly more patients on INEGY reached the optional LDL-C goal of <70 mg/dL at all dose comparisons compared with those taking rosuvastatin (p<0.05).(2) INEGY and rosuvastatin were well tolerated at all doses in the study.(1)

"Reducing LDL cholesterol to goal, such as the NCEP ATP III target or the goal set by the ESC (i.e.,<2.5mmol/l), is of the highest importance," said Professor Alberico Catapano, Professor of Pharmacology, University of Milan, Italy, an investigator and study author. "Many patients with hypercholesterolemia do not meet such goals using a recommended statin dose, even with a highly effective statin. These patients may require an increase in statin dose. However, doubling a statin dose yields an average of only six percent additional reduction in LDL-C. This study shows that clinicians can set a new standard in LDL-cholesterol treatment by treating two sources of cholesterol using ezetimibe/simvastatin, thus providing patients with significantly greater LDL cholesterol control."

INEGY provided greater LDL-C reduction than rosuvastatin across the dose range and at each dose comparison

The study, which was a multicenter, double-blind, six week, parallel-group study was carried out in 2,959 patients who were randomized equally to one of six arms: INEGY (ezetimibe/simvastatin) 10/20 mg, 10/40 mg, 10/80 mg, or rosuvastatin 10 mg, 20 mg, or 40 mg. The primary endpoint was LDL-C reduction from baseline averaged across all doses, and key secondary endpoints included LDL-C reductions from baseline at each dose comparison. (The modified intent-to-treat population included 2,855 patients.)

Results showed that INEGY provided significantly greater LDL-C reduction compared to rosuvastatin when averaged across all doses (-4.2 per cent, p<0.05), and at individual dose comparisons (rosuvastatin 10 vs. INEGY 10/20 = -5.7; rosuvastatin 20 vs. INEGY 10/40 = -2.5; rosuvastatin 40 vs. INEGY 10/80 = -4.3; p<0.05 for each arm). These results indicate that greater LDL-C reductions are experienced with INEGY through treating two sources of cholesterol - absorption in the intestine and production** in the liver.(1) Increases in HDL ("good") cholesterol were comparable between INEGY and rosuvastatin at all doses in this study. INEGY and rosuvastatin were well tolerated in all treatment groups.(1)

**NCEP ATP III is the U.S. National Cholesterol Education Program Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults, a set of guidelines for effective patient identification, assessment, diagnosis, and treatment.

A greater proportion of high-risk patients achieve LDL-C <70 mg/dL with INEGY compared to rosuvastatin

A secondary endpoint in the same study compared LDL-C target attainment (<100 mg/dL or <70 mg/dL), among 715 high risk patients (i.e., those with CHD or CHD risk equivalent by NCEP ATP lll)

Results showed that INEGY was superior to rosuvastatin for achievement of LDL-C optional target of 70 mg/dL in high risk patients (overall 50.1 per cent with INEGY compared to 29.4 per cent with rosuvastatin; P<0.05).(2)

In addition, numerically more of these high risk patients were able to reach their NCEP ATP III LDL-C goal <100 mg/dL (overall 90.1 per cent with INEGY compared to 82.0 per cent with rosuvastatin; p<0.05).(2)

Treating two sources of cholesterol through Dual Inhibition

Cholesterol in the body originates from two main sources: absorption in the intestine of both biliary and dietary cholesterol, and production in the liver and peripheral tissues.(3,4) Approximately two-thirds of intestinal cholesterol comes from biliary sources; one third comes from dietary sources.(5) Approximately 50 percent of cholesterol in the intestine is absorbed and re-circulated in the blood; the remainder is excreted.(6) Cholesterol-lowering agents (statins) reduce cholesterol levels through the partial inhibition of one pathway; that is, by inhibiting the production (synthesis) of cholesterol in the liver. INEGY contains the statin simvastatin, plus the active ingredient of EZETROL™ (ezetimibe), the first and only cholesterol absorption inhibitor which works by inhibiting intestinal absorption of cholesterol. INEGY is the first single product to powerfully target two sources of cholesterol through Dual Inhibition of cholesterol production and absorption, providing greater LDL-C reduction and allowing more hypercholesterolemia patients to reach their NCEP ATP III targets.(1,2)

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Article adapted by Medical News Today from original press release.
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About INEGY
INEGY has been developed and is being marketed by Merck & Co., Inc., Whitehouse Station, N.J., USA (NYSE: MRK) and Schering-Plough Corporation (NYSE: SGP) in connection with a partnership formed by both companies to develop and market worldwide (excluding Japan) new prescription medicines in cholesterol management.

Branded as INEGY in Europe, Middle East and Africa, the product is indicated (in the EU) as adjunctive therapy to diet for use in patients with primary (heterozygous familial and non-familial) hypercholesterolemia or mixed hyperlipidemia where use of a combination product is appropriate:

1) patients not appropriately controlled with a statin alone; and
2) patients already treated with a statin and ezetimibe.

INEGY has an additional indication for homozygous familial hypercholesterolemia. It has been approved in more than 50 nations around the world including the United States, where the Food and Drug Administration approved it in 2004 - under the brand name VYTORIN - for the treatment of high LDL cholesterol as adjuvant therapy to diet. The tolerability profile of INEGY is similar to simvastatin or atorvastatin and is maintained over long-term therapy.

About Merck
Merck & Co., Inc., which operates in many countries as MSD (Merck Sharp & Dohme), is a global research-driven pharmaceutical company dedicated to putting patients first. Established in 1891, Merck currently discovers, develops, manufactures and markets vaccines and medicines to address unmet medical needs. The Company devotes extensive efforts to increase access to medicines through far-reaching programs that not only donate Merck medicines but help deliver them to the people who need them. Merck also publishes unbiased health information as a not-for-profit service. For more information, visit http://www.merck.com/

About Schering-Plough
Schering-Plough Corporation is a global science-based health care company with leading prescription, consumer and animal health products. Through internal research and collaborations with partners, Schering-Plough discovers, develops, manufactures and markets advanced drug therapies to meet important medical needs. Schering-Plough's vision is to earn the trust of the physicians, patients and customers served by its more than 30,000 people around the world. The company is based in Kenilworth, N.J., and its Web site is http://www.schering-plough.com.

This press release contains "forward-looking statements" as that term is defined in the Private Securities Litigation Reform Act of 1995. These statements are based on management's current expectations and involve risks and uncertainties, which may cause results to differ materially from those set forth in the statements. The forward-looking statements may include statements regarding product development, product potential or financial performance. No forward-looking statement can be guaranteed, and actual results may differ materially from those projected. Merck undertakes no obligation to publicly update any forward-looking statement, whether as a result of new information, future events, or otherwise. Forward-looking statements in this press release should be evaluated together with the many uncertainties that affect Merck's business, particularly those mentioned in the cautionary statements in Item 1 of Merck's Form 10-K for the year ended Dec. 31, 2005, and in its periodic reports on Form 10-Q and Form 8-K, which the Company incorporates by reference.

References
1. Current Medical Research and Opinion (CMRO) 2006, Vol. 22 Issue 10: 2041 - 2053.

2. Shepherd J. The role of the exogenous pathway in hypercholesterolemia. Eur Heart J Suppl 2001;3(suppl E):E2-E5.

3. Van Heek M, Farley C, Compton DS et al. Comparison of the activity and disposition of the novel cholesterol absorption inhibitor, SCH58235, and its glucuronide, SCH60663. Br J Pharmacol 2000;129:1748-1754.

4. Wilson MD, Rudel LL. Review of cholesterol absorption with emphasis on dietary and biliary cholesterol. J Lipid Res 1994; 35:943-955.

5. Clearfield MB. A novel therapeutic approach to dyslipidemia. J Am Osteopath Assoc 2003;103(suppl 1):S16-S20.

6. Bays H. Ezetimibe. Expert Opin Investig Drugs. 2002;11(11):15 87-1604.

The data has been published in the October issue of the international journal Current Medical Research and Opinion