FDA approves two-in-one cholesterol-lowering drug

Washington -- Two pharmaceutical companies are set to begin marketing a new blended medication they say lowers harmful LDL cholesterol as sharply as the most popular high-dose statin alone.

Vytorin (ezetimibe/simvastatin) was approved by the Food and Drug Administration July 23 and is expected to be available by Labor Day at the latest, said company officials.

The new medication is a combination of Schering-Plough's Zetia (ezetimibe) which blocks the absorption of cholesterol in the intestines and Merck & Co. Inc.'s Zocor (simvastatin), a traditional statin that cuts cholesterol production in the liver.

Cholesterol-lowering medication in general is attracting additional interest since an updated version of federal cholesterol guidelines was released last month. Citing new research on the health benefits of lowering LDL cholesterol, this latest round of recommendations offers physicians the option of striving for even lower LDL levels among patients at high risk for heart attacks.

The guidelines lowered target levels from 100 mg/dL, to 70 mg/dL for patients who have coronary heart disease or diabetes or for those who smoke and have hypertension.

The change in advice could add millions of additional patients to the enormous group already taking cholesterol medication, predominately statins.

Thus, Vytorin's introduction is expected to touch off a price and advertising war in the profitable multibillion dollar anticholesterol drug market.

The drug will be promoted to physicians and their patients as a first-line agent to use when LDL cholesterol is not lowered sufficiently by changes in diet and exercise, said company officials.

"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, chair, president and chief executive officer of Merck.

The drug, which will be available in 10 mg doses of Zetia and varying doses of Zocor, is expected to be marketed as an alternative to the best-selling statin, Lipitor (atorvastatin), which is marketed by Pfizer Inc.

Company data on Vytorin show that it lowered LDL cholesterol by 52% at its recommended starting dose of 10 mg of Zetia and 20 mg of Zocor. An 80 mg dose of Lipitor can reduce LDL levels by about 60%, according to information on Pfizer's Web site.

Vytorin will cost about $70 per month for all strengths. In comparison, a monthly prescription of Lipitor costs at least $100.

High-dose dilemma

Although the new drug is poised to make a dent in sales of individual statins, physicians should consider the much longer track record of the well-studied statins before switching patients to Vytorin, cautions Eric Topol, MD, co-director of the Cleveland Clinic's Heart Center.

"I think it's been hyped up," he said of the newcomer. "Statins have been shown to have extraordinary benefits, but we don't know if this combination with ezetimibe is the same as a statin effect." Zetia gained FDA approval in Oct. 2002.

In addition, statins do a lot more than just lower cholesterol, said Dr. Topol. "They have a potent anti-inflammatory effect as well."

Statins have been shown to have a beneficial effect on multiple sclerosis and in rheumatoid arthritis, he said, and in other areas "where LDL lowering isn't even a part of the story."

Although company trials show that Vytorin lowers LDL cholesterol, there are no trials to show it reduces death, heart attack or stroke as there are for statins, said Dr. Topol. The new drug could have a place in the physician's toolbox, he added. But it should be held in reserve for those patients who can't tolerate statins at a dose high enough to sufficiently lower their LDL levels, he said. "It should be used as a fallback. You just don't have the same level of comfort as you would if you could achieve that with statins alone."

Although statins are generally very safe, higher doses are associated with additional side effects, and some physicians like the fact that the Vytorin combination can lower LDL levels using a less potent statin. In addition, doubling the dose of a statin on average lowers LDL cholesterol only an additional 6%.

Pointing to the new federal guidelines, Christopher Cannon, MD, associate professor at Harvard Medical School and a cardiologist at Brigham and Women's Hospital in Boston, welcomed approval of the new drug. "Many people will need a strong drug like this in order to reach those new goals." In addition, he noted the convenience factor of having both drugs in one pill. "It makes it simple for patients and doctors to reach cholesterol levels that prevent heart attacks."

John LaRosa, MD, president of SUNY Downstate Medical Center in Brooklyn, noted that patients are more likely to adhere to a drug routine if it is simple. "The two things that best predict whether people take what is prescribed is the frequency that it has to be taken during a 24-hour period and the number of medications they have to take," he said. Vytorin is taken once a day as are statins.

Dr. LaRosa also cautioned that he wouldn't want the drug to be prescribed for the wrong reason, namely that physicians are afraid to prescribe higher doses of statins. "Approved doses of statins have very acceptable side effects, even at the higher dose."