Healthcare Industry News: ezetimibe
News Release - March 26, 2007
Merck and Schering-Plough to Develop Another New Cholesterol Lowering MedicineNew Medicine Will Be Fixed Dose Combination of ezetimibe and Atorvastatin
WHITEHOUSE STATION, N.J.--(HSMN NewsFeed)--Merck & Co., Inc. (NYSE: MRK ) announced today an agreement to commence development of an ezetimibe and atorvastatin combination product in collaboration with Schering-Plough Corporation.
Merck and Schering-Plough are the two parent companies of Merck/Schering-Plough Pharmaceuticals, a joint venture that was formed in 2000 to develop and market in the United States new prescription medicines in cholesterol management and respiratory disease. The cholesterol collaboration was expanded in 2001 and includes worldwide markets (excluding Japan). The joint venture/partnership also markets ZETIAŽ (ezetimibe) and VYTORINŽ (ezetimibe/simvastatin) in the U.S. and these medicines are marketed as EZETROL and INEGY, respectively, in many countries outside the U.S.
"Everyone at Merck is delighted that we have entered into this agreement with Schering-Plough," said Richard T. Clark, president and chief executive officer of Merck & Co., Inc. "This agreement exemplifies Merck's Plan to Win by expanding our lead in cutting-edge science through investments in our own internal research as well as through external collaborations and is a logical next step for our very strong and successful partnership with Schering-Plough."
The development program is timed such that this combination product could be available at the time that patent exclusivity for atorvastatin expires in the U.S. and internationally.
The cholesterol-management market is one of the largest worldwide, with total worldwide sales of $32 billion (IMS Full Year 2006 Constant USD) and sales in the U.S. of $22 billion in 2006 (IMS Health).
"Based on the outstanding performance of VYTORIN and INEGY in markets around the world, the excellent LDL cholesterol efficacy and wide acceptance of the dual inhibition approach to the treatment of elevated cholesterol has clearly been established. The development of ezetimibe and atorvastatin is an extension of this approach," said Peter Loescher, president, Global Human Health, Merck & Co., Inc.
ZETIA, which works in the digestive tract to inhibit the absorption of cholesterol, is complementary to the class of cholesterol-lowering agents known as statins, which work in the liver to reduce the production of cholesterol. In a multi-center, double blind, placebo controlled 12-week clinical trial in 628 patients with high cholesterol, the co-administration of atorvastatin (10 mg, 20 mg, 40 mg, 80 mg) with ZETIA 10mg lowered LDL "bad" cholesterol by an average of 53 to 61 percent from baseline across the dosing range compared to average LDL cholesterol reductions of 37 to 54 percent with atorvastatin alone. ZETIA, either alone or in addition to a statin, has not been shown to prevent heart disease or heart attacks.
ZETIA is indicated, along with a healthy diet, for use either by itself or together with statins in patients with high cholesterol to reduce LDL cholesterol and total cholesterol when the response to diet has been inadequate. It is also available in a once-daily tablet with Zocor (simvastatin), a Merck statin and marketed under the brand names VYTORIN in the United States and INEGY internationally.
Important information about ZETIA
ZETIA is a prescription medication and should not be taken by people who are allergic to any of its ingredients. When ZETIA is prescribed with a statin, it should not be taken by women who are nursing or pregnant or who may become pregnant, or by anyone with active liver disease. Statins should not be taken by anyone with these conditions. If you have ever had liver problems or are pregnant or nursing, your doctor will decide if ZETIA is right for you. Your doctor may do blood tests to check your liver before you start taking ZETIA with a statin and during treatment.
Due to the unknown effects of increased exposure to ZETIA in patients with moderate or severe hepatic insufficiency, ZETIA is not recommended in these patients. In clinical trials, there was no increased incidence of myopathy (muscle pain) or rhabdomyolysis (muscle breakdown) associated with ZETIA; however myopathy and rhabdomyolysis are known adverse reactions to statins and other lipid-lowering drugs.
There are no adequate and well-controlled studies of ZETIA in pregnant women. ZETIA should not be used in pregnant or nursing women unless the benefit outweighs the potential risks.
When ZETIA was co-administered with a statin, consecutive elevations in liver enzymes, more than three times the upper limit of normal, were slightly higher than those with the statin alone (1.3 percent vs. 0.4 percent). These elevations were generally asymptomatic and returned to baseline after discontinuation of therapy or with continued treatment. When ZETIA was co-administered with fenofibrate, consecutive elevations in liver enzymes more than three times the upper limit of normal, were 2.7 percent, and 4.5 percent in patients treated with fenofibrate alone. Caution should be exercised when initiating ZETIA in patients treated with cyclosporine, particularly in patients with severe renal insufficiency, due to increased blood levels of ZETIA.
In clinical trials, most frequent side effects for ZETIA alone versus placebo included: back pain (4.1 percent vs. 3.9 percent), arthralgia (3.8 percent vs. 3.4 percent), and fatigue (2.2 percent vs. 1.8 percent); for ZETIA plus statin versus statin or placebo alone: back pain (4.3 percent vs. 3.7 percent vs. 3.5 percent), abdominal pain (3.5 percent vs. 3.1 percent vs. 2.3 percent), and fatigue (2.8 percent vs. 1.4 percent vs. 1.9 percent).
Important information about VYTORIN
VYTORIN contains simvastatin and ezetimibe. VYTORIN is indicated as adjunctive therapy to diet when diet alone is not enough, for the reduction of elevated total cholesterol, LDL cholesterol, Apo B(1), triglycerides and non-HDL cholesterol and to increase HDL cholesterol in patients with primary (heterozygous familial and non-familial) hypercholesterolemia or mixed hyperlipidemia. No incremental benefit of VYTORIN on cardiovascular morbidity and mortality over and above that demonstrated for simvastatin has been established.
VYTORIN is also indicated for the reduction of elevated total cholesterol and LDL cholesterol in patients with homozygous familial hypercholesterolemia, as an adjunct to other lipid-lowering treatments (e.g. LDL apheresis) or if such treatments are unavailable.
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.
Selected cautionary information for VYTORIN
Muscle pain, tenderness or weakness in people taking VYTORIN should be reported to a doctor promptly because these could be signs of a serious side effect. VYTORIN should be discontinued if myopathy is diagnosed or suspected. To help avoid serious side effects, patients should talk to their doctor about medicine or food they should avoid while taking VYTORIN.
In three placebo-controlled, 12-week trials, the incidence of consecutive elevations (=>3 X ULN) in serum transaminases were 1.7 percent overall for patients treated with VYTORIN and 2.6 percent for patients treated with VYTORIN 10/80 mg. In controlled long-term (4 -week) extensions, which included both newly-treated and previously-treated patients, the incidence of consecutive elevations (=>3 X ULN) in serum transaminases was 1.8 percent overall and 3.6 percent for patients treated with VYTORIN 10/80 mg. These elevations in transaminases were generally asymptomatic, not associated with cholestasis and returned to baseline after discontinuation of therapy or with continued treatment. Doctors should perform blood tests before, and periodically during treatment with VYTORIN when clinically indicated to check for liver problems. People taking VYTORIN 10/80 mg should receive an additional liver function test prior to and three months after titration and periodically during the first year.
Due to the unknown effects of increased exposure to ezetimibe (an ingredient in VYTORIN) in patients with moderate or severe hepatic insufficiency, VYTORIN is not recommended in these patients. The safety and effectiveness of VYTORIN with fibrates have not been established; therefore, co-administration with fibrates is not recommended. Caution should be exercised when initiating VYTORIN in patients treated with cyclosporine and in patients with severe renal insufficiency.
VYTORIN has been evaluated for safety in more than 3,800 patients in clinical trials and was generally well tolerated at all doses (10/10 mg, 10/20 mg, 10/40 mg, 10/80 mg). In clinical trials, the most commonly reported side effects, regardless of cause, included headache (6.8 percent), upper respiratory tract infection (3.9 percent), myalgia (3.5 percent), influenza (2.6 percent) and extremity pain (2.3 percent).
Merck & Co., Inc. is a global research-driven pharmaceutical company dedicated to putting patients first. Established in 1891, Merck currently discovers, develops, manufactures and markets vaccines and medicine 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 www.merck.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, 2006, and in its periodic reports on Form 10-Q and Form 8-K, which the Company incorporates by reference.
(1) Apo B is the protein component of lipoproteins, LDL and VLDL, which carry cholesterol in the blood.
ZETIAŽ and VYTORINŽ are registered trademarks of MSP Singapore Company LLC.
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