A joint FDA panel decision to recommend against approval of over-the-counter Mevacor Daily was tempered by the endorsement of a behind-the-counter drug class by a number of panelists.

The agency's Nonprescription Drugs and Endocrinologic & Metabolic Drugs advisory committees voted 20-3 against approval of an Rx-to-OTC switch of J&J/Merck's cholesterol-lowering agent.

"I think that the behind-the-counter option would be a perfect solution to this dilemma," said pediatrician Leslie Clapp, MD, joining many panelists who voiced support for a "pharmacy-only" approach while voting against OTC approval.

"Mevacor seems to be crucial in heart health, and a great drug for it," Clapp explained. However, widespread OTC marketing would "shift the risk-benefit ratio" of the drug because of inappropriate self-selection, Clapp maintained.

"I'm hoping that the FDA will have some solution for the future of changing access to over-the-counter medicines to behind-the-counter as they do in the UK."

Many panelists who objected to a switch maintained Mevacor 20 mg is safe and effective for the targeted population, but voiced concerns about the public health impact of a switch.

The appropriate population is "a moving target, and I'm not convinced that patients who fall outside that target are properly channeled where they should be if they fail to reach goal or if new conditions develop," said EMDAC member Nelson Watts, MD, University of Cincinnati.

"I'm not at all convinced that patients can self-select for the target population. Considerable help from health professionals is needed, and that's why it's a prescription drug," Watts said.

Mevacor Daily is indicated for consumers with LDL cholesterol between 130 and 170 mg/dL, in addition to other CHD risk factors.

"There needs to be better care available in terms of pharmacist care, or someone to ensure that there is better follow up," maintained NDAC panelist Neil Benowitz, MD, University of California-San Francisco.

In all, nine panelists cited the British "P" designation or pharmacy class as a desirable model for statin marketing.

The UK approved Merck's Zocor for pharmacy class sale in May 2004.

There is some support within FDA for creation of a third class of drugs model in the U.S., Charles Ganley, MD, director of FDA's Division of OTC Drug Products acknowledged during an interview following the meeting.

Establishment of a third class likely would require legislative changes, as FDA's authority to approve drugs behind the counter is unclear, he allowed.

"I think clearly there would have to be some interpretation from our lawyers of whether they think we have that authority."

However, "I think that's something some of the folks at FDA are willing to look into," Ganley noted.

"I'm not sure that's the course we'll take in the time we have left to get the [Mevacor] review done," he said.

The OTC industry has consistently opposed the concept of a third drug class in the U.S.

Ganley expressed his personal opinion on the subject: "It's the option we ought to look at, particularly when you look at trying to control healthcare costs and trying to provide therapies to individuals who don't have the insurance coverage, or may not have prescription coverage."

"I think it's a realistic thing to try to look at. It may be an option that is a viable one in this country."

Panel objections to OTC status focused on Merck's CUSTOM actual-use trial and the small group of individuals able to accurately self-select for treatment.

Only 10% of lovastatin users in CUSTOM were in the appropriate target population as defined by label criteria, according to FDA's analysis of Merck's data.

Moreover, only 1% of consumers appropriately determined that they could begin using Mevacor "right away," the agency's interpretation of Merck's label comprehension study revealed.

J&J/Merck said it was "disappointed" with the outcome but "encouraged by the discussion and recognizes the vote of the committees reflected a wide range of opinions."

The firm says it will continue to pursue a switch.

The vote does not close the door on OTC statins, Ganley emphasized.

"I think the thing people should focus on isn't what the vote is, it's what the comments were around the vote," Ganley said. "I think there were a lot of very positive statements and though the vote may have seemed lopsided, I think there was clearly an encouragement to try to get this process forward."

For example, during the morning session the panel agreed unanimously that Mevacor would be effective in lowering cholesterol in the target population, and side effects related to toxicity should not preclude a switch of the drug.

The panel said the sponsor provided enough evidence from CUSTOM and previous Rx statin trials to support the cholesterol-lowering effects of the 20 mg dose of lovastatin.

Liver monitoring before or during use of the drug should not be required, the panel maintained.

Finally, the committee voted that risk of muscle toxicity was "acceptable" for use by consumers in an OTC setting.

The committee did express concern over whether Mevacor Dailyis appropriate for certain female populations, considering lovastatin carries risks for women of childbearing age.

All statins currently are labeled as pregnancy Category X, meaning they should not be used during pregnancy.

Nineteen members asserted the data did not present sufficient fetal toxicity concerns to prevent OTC marketing; five panelists disagreed with one abstention.

However, the panel agreed unanimously that Merck's proposed pregnancy labeling was inadequate.

Among those in favor of a switch was NDAC Chair Alastair Wood, MD, Vanderbilt University.

"The drug is safe and effective for use without the intervention of a doctor in the target population that it was designed to look at," Wood said.

"The reality is that the vast majority of these patients are receiving no therapy right now, and should be, and I think the idea that we should deny these patients therapy is disturbing to me."

Mevacor OTC Panel Rejection Elicits Third Drug Class Talk

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