Schering-Plough announces ZETIA spproved in Japan

Apr 20 2007

Schering-Plough Corporation has announced that Schering-Plough K.K., the company's country operation in Japan, has received marketing approval for ZETIA (ezetimibe), a novel cholesterol-lowering agent that inhibits the absorption of cholesterol in the intestine.

ZETIA is approved in Japan for use in patients with hypercholesterolemia, familial hypercholesterolemia or homozygous sitosterolemia. ZETIA can be used as a monotherapy and co- administered with a statin, for further reduction of LDL "bad" cholesterol in patients with hypercholesterolemia, familial hypercholesterolemia or homozygous sitosterolemia. ZETIA will not become available in Japan until National Health Insurance Reimbursement price listing.

"ZETIA has achieved worldwide recognition for its unique mechanism of action in lowering LDL cholesterol levels. The ezetimibe molecule represents an important innovation by Schering-Plough's scientists," said Robert J. Spiegel, M.D., chief medical officer and senior vice president of medical affairs, Schering-Plough Research Institute (SPRI). "ZETIA offers an advance for Japanese patients at risk for cardiovascular disease, and provides a new option in the physician's armamentarium for the treatment of elevated LDL cholesterol," Spiegel added.

Schering-Plough obtained FDA approval for ZETIA in 2002, and the medication has been approved in 90 countries worldwide. The cholesterol- management market is one of the largest worldwide, with total global sales of $34 billion and sales in the United States of $22 billion in 2006 (IMS Health). The total number of hypercholesterolemia patients in Japan, including those undiagnosed, is estimated to be approximately 30 million.

ZETIA will be co-marketed in Japan with Bayer Yakuhin Ltd., a global pharmaceutical company with a large expertise in cardiovascular disease- related products. Schering-Plough, in collaboration with Merck, has developed and commercialized ZETIA for lipid management in the United States and the rest of the world (excluding Japan).

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. ZETIA, alone or in combination with statins, has been proven to significantly improve LDL cholesterol levels. 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. ZETIA is also marketed under the trade name EZETROL 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%, and 4.5% 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 vs. 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 vs. 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).