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`FDA approves Zetia -- first new class to treat cholesterol since statins
`introduced
`WHITEHOUSE STATION & KENILWORTH, N.J., October 28, 2002 -- Following a 10-month review, the FDA has
`approved Zetia (ezetimibe), the first in a new class of cholesterol-lowering agents that inhibit the intestinal absorption
`of cholesterol.
`
`Merck/Schering-Plough Pharmaceuticals announced that the once-daily tablet of Zetia 10 mg was approved for use
`either by itself or together with statins in patients with high cholesterol, to reduce both LDL ("bad") cholesterol and
`total cholesterol.
`
`Cholesterol-lowering medicines are recommended for use, in addition to an appropriate diet, when the response to
`diet and exercise has been inadequate.
`
`In clinical trials, Zetia was generally well tolerated with an overall side effect profile similar to placebo.
`
`"Sixty percent of the estimated 13 million patients taking statins continue to have LDL cholesterol higher than
`recommended levels," said H. Bryan Brewer, M.D., chief of the molecular disease branch, National Heart, Lung and
`Blood Institute, National Institutes of Health (NIH).
`
`"As the first breakthrough to treat cholesterol since statins were introduced 15 years ago, Zetia provides physicians
`with a new option to get more of these patients to goal. This is particularly important in view of last year's changes to
`the NIH's cholesterol guidelines, which substantially expand the number of Americans eligible for drug therapy and
`call for lower cholesterol goals for many patients," he said.
`
`"Discovered by Schering-Plough scientists and developed in partnership with Merck, Zetia offers patients an
`important therapeutic advance in the treatment of high cholesterol," said Richard Jay Kogan, Chairman and CEO of
`Schering-Plough.
`
`Zetia has a unique, complementary mechanism of action. Cholesterol in the blood is controlled primarily by two
`organs: the liver, which produces cholesterol and bile acids (which are used in digestion); and the intestine, which
`absorbs cholesterol both from food and from the bile (made by the liver). Zetia lowers cholesterol through a unique
`mechanism of action by inhibiting cholesterol absorption in the intestine.
`
`This mechanism of action makes Zetia complementary to statins, which work in the liver. Therefore, patients who take
`Zetia with a statin can achieve additional reductions in LDL and total cholesterol. The mechanism of Zetia is also quite
`different from a currently available class of drugs known as "bile acid sequestrants," which lower cholesterol by
`physically binding to bile acids in the small intestine.
`
`In a pivotal, multi-center study known as the "Add-On" study, patients who had not reached their LDL cholesterol goal
`on a stable dose of a statin alone had Zetia or placebo added to their statin regimen. The statin dose remained
`constant. The study showed that adding Zetia to ongoing statin treatment provided a 25 percent (36 mg/dL) additional
`reduction in LDL cholesterol versus 4 percent (6 mg/dL) with the addition of placebo. Mean LDL cholesterol levels of
`patients on statin therapy dropped from 138 mg/dL to 102 mg/dL when Zetia was added versus a drop from 139
`mg/dL to 133 mg/dL when placebo was added.
`
`Most of the response in LDL cholesterol reduction was seen within two weeks of adding Zetia and the additive
`reduction provided by Zetia was generally consistent across all statins tested.
`
`Another important endpoint of the "Add-On" study was the percentage of patients who reached the National
`
`CFAD Ex. 1017 (1 of 2)
`
`

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`Cholesterol Education Program (NCEP) II target LDL cholesterol goal when either Zetia or placebo was added to their
`ongoing statin therapy. The study showed that 72 percent of the patients who were not at goal on their statin dose at
`baseline reached goal when Zetia was added, compared to 19 percent of patients with the addition of placebo.
`
`Zetia delivered significant reductions in LDL cholesterol when co-administered with all statins tested, including Lipitor
`and Zocor.
`
`The U.S. approval of Zetia was also based on four placebo-controlled co-administration studies, in which Zetia and
`either Lipitor (atorvastatin), Zocor (simvastatin), Pravachol (pravastatin) or Mevacor (lovastatin) were started together
`in previously untreated patients with high cholesterol levels.
`
`Zetia co-administered with Lipitor and Zocor further improved triglycerides and HDL ("good") cholesterol.
`
`The FDA also approved Zetia for use in two rare genetic disorders: homozygous familial hypercholesterolemia and
`homozygous sitosterolemia. In homozygous familial hypercholesterolemia, Zetia, administered with Lipitor or Zocor, is
`indicated for the reduction of elevated total cholesterol and LDL cholesterol as an adjunct to other lipid-lowering
`treatments.
`
`In sitosterolemia, Zetia is indicated as adjunctive therapy for the reduction of elevated sitosterol and campesterol
`levels in addition to diet. Zetia is the only medicine approved for this serious condition.
`
`Source: Merck/Schering-Plough Pharmaceuticals
`
`Posted: October 2002
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`CFAD Ex. 1017 (2 of 2)