FDA panel votes against Mevacor Daily OTC switch

SILVER SPRING, Md. —It’s safe. It’s effective. But again it was the lack of appropriate self-selection that scuttled Merck’s third attempt at switching its Mevacor statin from prescription to over-the-counter status.

A pair of Food and Drug Administration advisory panels last month voted 10-2 (with one abstention) against the switch of Merck’s Mevacor 20 mg, suggesting that a statin will not be switched to OTC in this country. While the FDA may yet approve Mevacor Daily—the chosen trade name for the OTC lovastatin—the agency only acts against the advice of its advisory panels on rare occasions.

The anticipated action date on whether to approve an OTC Mevacor Daily is slated for Jan. 26, Merck has reported.

While Merck improved self-selection scores in a consumer label-comprehension study from two years ago, FDA advisers raised concerns that a few patients reported they would substitute an OTC statin in place of their prescribed statin, suggesting that they may move from being adequately protected against potential heart disease to underprotected.

“The switching issue is the one that’s troubling,” said one member of the panel. “If you switch from a stronger prescription medicine, if you use [Mevacor Daily] instead, to me that would be much more likely to happen if this over-the-counter drug was very cheap,” he said.

Even new partner GlaxoSmithKline, which signed on to the Mevacor switch team as the consumer healthcare distributor a month before the FDA meeting, could not sway the majority of advisory panelists from nay to yea.

“GlaxoSmithKline has a [proven] track record…for first-in-class switches,” noted George Quesnelle, president of consumer healthcare for North America for GlaxoSmithKline, during his presentation in support of the switch. As examples, Quesnelle pointed to the company’s successful switch of such complicated regimens as smoking cessation products and the diet aid Alli. If switched, non-branded education to help raise awareness around statins will be launched into the marketplace, Quesnelle said, long before Mevacor Daily actually hits shelves.

Merck’s new studies found that more consumers correctly self-selected as compared with 2005. “For the small fraction that made a mistake” the chance of a serious adverse event is extremely low, noted Edwin Hemwall, Merck’s executive director of worldwide OTC regulatory and scientific affairs. Indeed, consumers approached a 90-percent level in making appropriate decisions regarding the use of Mevacor Daily, Hemwall said.

“We know that Mevacor Daily is indicated for a motivated, [health-conscious] consumer,” Quesnelle said. GlaxoSmithKline’s marketing initiatives were submitted along with the application, he added.

To help consumers with self-selection, Merck made label revisions, including a highlighted age-exclusion graphic on the front of the package and a stronger warning against the use of Mevacor Daily in women who are pregnant or could become pregnant.

Merck presented usage studies of two labels—one that asked consumers to evaluate whether they should take Mevacor Daily based in part on their knowledge of their total cholesterol scores and one that based that evaluation on a consumer’s low-density lipid levels. Merck concluded that consumers were more familiar with their total cholesterol levels.

Merck also proposed selling Mevacor Daily “on the open shelf but only in those stores with pharmacies.” Limiting distribution to stores with pharmacies affords the consumer convenient access to a healthcare professional should they have questions.

However, the new studies did not alleviate all of the FDA’s concerns over appropriate self-selection. In the usage study based on a consumer’s knowledge of their LDL levels, for example, 98 percent of consumers appropriately chose not to take the medicine, but only 16 percent of those who chose to take the medicine did so appropriately.

In addition, more than 30 percent of participants who already were taking a lipid-lowering drug stated that it would be appropriate for them to use an OTC statin. Of those, 55 percent would replace their current lipid therapy with the Mevacor Daily, and 28 percent would take Mevacor Daily in conjunction with their current statin therapy. Half of those already on a statin regimen would make the switch to Mevacor Daily based on cost concerns, with the assumption that an OTC medicine would be cheaper than their prescription-drug co-pays; 29 percent cited improved convenience in buying Mevacor over-the-counter; 15 percent said an OTC statin would mean they wouldn’t have to see their doctor as often; and 11.3 percent opined that OTC medicines present fewer side effects than their prescription-only drugs.

“I was…concerned about the reasons why people decided they would rather have an OTC [statin],” commented Mary Tinetti, chairman of both the meeting and the nonprescription drugs advisory committee. “Things like…it was ‘safer and more natural [because it was OTC].’ Obviously, that’s not the case. It just tells us that at this point we’re not in a situation where people can make that [qualitative] decision.”

“We felt we presented a compelling case to the committee that nonprescription Mevacor 20 mg would be a valuable option for motivated consumers who know they have moderately elevated cholesterol and certain risk factors and are already talking with their healthcare provider,” stated Edwin Hemwall, Merck’s vice president of global OTC regulatory and scientific affairs.

The next question is whether Merck will make a fourth switch pitch for its Mevacor statin. A GlaxoSmithKline spokesman declined to speculate on that possibility following the vote, though with the last-minute addition of GSK to the switch process, a fourth attempt benefiting from GSK’s switch expertise may be in the realm of possibility.

The FDA certainly wouldn’t object. When asked during a press conference if the latest vote against an OTC Mevacor amounted to “three strikes and you’re out,” Andrea Leonard-Segal, FDA director of the nonprescription clinical evaluation division of the office of nonprescription products, said no. “We are open-minded [at the FDA],” she said.