FDA panel rejects sales of Mevacor over counter

BETHESDA, Md. -- Federal advisers rejected Merck & Co.'s quest to become the first American drug maker to sell cholesterol-fighting statins over the counter, saying the company's own studies raised potential health risks while offering modest life-saving benefits.

The majority of the panel, which advises the Food and Drug Administration, wasn't ready to knock down all barriers for potent medications that advocates credit with saving thousands of lives per year.

The panel suggested the agency take a more restrained step, asking the FDA to mimic in the United States a system used successfully in England. So-called behind-the-counter sales in England provide drugs to consumers without prescription and require guidance by a pharmacist, but not by a doctor.

The FDA, however, said it has never approved -- nor has it received -- such an application in recent memory.

Merck spokesman Tony Plohoros said the company and its marketing partner, Johnson & Johnson, were ''disappointed with the outcome of the deliberations." He said the company continues to believe that over-the-counter sales of the statin drug, Mevacor, would ''help lower cholesterol and contribute to improved public health."

The panel's decision marked the second time Mevacor was rejected for over-the-counter sales. Statins reduce levels of ''bad" cholesterol while modestly boosting ''good" cholesterol.

The FDA will formally rule on Merck's application by Feb. 24. It does not have to follow its advisory panel's recommendations, but often does.

Federal advisers questioned Merck's analysis, noting that the bulk of consumers who tried Mevacor without a prescription in a trial did so even though they failed to meet the two most crucial label requirements: age and cholesterol levels.

Some women too young to fit the label criteria were of child-bearing age, raising worries since animal studies linked Mevacor to severe birth defects. And some people who tried the drug during a 26-week trial sponsored by Merck and Johnson & Johnson had cholesterol levels that were too high for the drug.

Using a 20 mg over-the-counter dose of Mevacor instead of a more potent prescription dose potentially carries its own health risk: nine extra heart attacks and strokes suffered per 100 people taking the wrong dose for a decade, said Dean Follman, a biostatistician at the National Institutes of Allergy and Infectious Diseases in Bethesda, Md.

The panel, made up of 25 doctors, statisticians, pharmacists, and other medical experts, weighed their actions carefully.

The panel felt that over-the-counter approval of Mevacor would lead to scores of other products to reduce bad cholesterol, tame high blood pressure, and keep diabetes in check. Because the precedent they set for Mevacor would apply to a long line of other drugs, they pushed for more rigorous studies.

According to Merck, some 23 million Americans have moderately high cholesterol levels. Of that group, Merck expected to target up to 15 million at moderate risk for heart disease who are not taking a prescription drug. The company said it expected to nibble at that ''treatment gap" by attracting just a few million consumers with its over-the-counter product.

Federal advisers were skeptical, saying an expected marketing blitz would put Mevacor in more hands than Merck acknowledged, including some inappropriate candidates.

In animal studies, lovastatin, as the drug is known generically, was linked to fetal deaths, malformed skeletons, and behavioral delays, according to Karen Davis-Bruno, a FDA supervisory pharmacologist. The FDA could not definitively link side effects reported by pregnant women who took lovastatin in their first trimester, but pregnant women are barred from taking the prescription product.

Doctors can police that restriction. Worries rise with over-the-counter sales, since no doctor's advice is needed.

Indeed, 1 percent of the women who took Mevacor in Merck's most recent trial were younger than 45, said Sonia Patten, a consumer representative on the panel. According to the March of Dimes, half of all pregnancies among American women are unplanned.

''Increasing maternal ages and widespread public recognition of statins may increase the likelihood of statin use during pregnancy," according to testimony presented to the panel by Dr. Nancy Green, the White Plains, N.Y., organization's medical director.

Dr. Frank Davidoff, a Connecticut internist, took Merck to task for simply focusing on how the drug reduces cholesterol. A better statistic would be the absolute risk reduction for people suffering cardiovascular events, data that were not presented, he said. Instead of selling Mevacor over the counter in a ''massive uncontrolled experiment," Davidoff said he wanted to see those studies.

A vocal minority said the company's application deserved approval to offer treatment to people who need to lower cholesterol but lack insurance to pay for pricier prescription cholesterol drugs.

''The reality is the vast majority of these patients are receiving no therapy right now and should," said Dr. Alastair Wood, a Vanderbilt University medical professor who was the panel's chair. ''The idea that we should deny these patients therapy is disturbing."

Diedtra Henderson can be reached at dhenderson@globe.com.