FDA may be moving toward softening its firm stance, announced in a 1997 guidance, against over-the-counter use of cholesterol-lowering drugs.

The agency's Nonprescription Drugs and Endocrinologic & Metabolic Drugs Advisory Committees are scheduled to meet jointly July 13-14, reportedly to consider one or more applications to switch a statin Rx drug to OTC status.

In addition, FDA is said to be contemplating holding a meeting in late May that will examine the potential for OTC treatment of chronic, long-term conditions that require interaction between patient and physician.

Potential issues to be raised by FDA in one or both of these meetings could include physician diagnosis, total cholesterol levels and measurements as compared to those of subcomponents, and condition management.

In the October 1997 guidance, FDA said it concurred with the recommendations of the two committees that hypercholesterolemia treatment requires both preliminary and ongoing medical management and, consequently, is not suitable as an OTC indication.

The advisory committees' findings and the 1997 guidance stemmed from Bristol-Myers Squibb's failed attempts to switch Questran (cholestyramine). The agency issued the guidance, in part, to advise companies against expending resources to switch cholesterol-lowering drugs.

The guidance, however, has come under heavy industry criticism, and various FDAers confirmed that "no" simply meant no at the time of the guidance, and that certain technological and scientific advances could alter the agency's position.

At a December meeting sponsored by the Food & Drug Law Institute, Center for Drug Evaluation & Research Director Janet Woodcock, MD, said the agency would re-examine the question of potential Rx-to-OTC switches for cholesterol-lowering drugs in 2000 (¹ Also see "OTC Cholesterol Drugs May Be Revisited By FDA In 2000" - Pink Sheet, 20 December, 1999.).

Merck's joint venture with Johnson & Johnson is evaluating Mevacor (lovastatin) as a possible switch candidate and is testing the drug in subjects with slightly elevated cholesterol (² Also see "J&J/Merck Mevacor Tests Include Subjects With Slightly Elevated Cholesterol" - Pink Sheet, 12 April, 1999.).

In March 1999, Mevacor was the first statin to receive FDA approval for the primary prevention of coronary heart disease in patients with normal or slightly elevated total cholesterol levels and no symptomatic cardiovascular disease. The new condition was thought to help bolster the company's argument for a switch.

An OTC application presumably would seek approval for use of Mevacor in a population similar to that covered by the new supplemental indication. Marketing exclusivity for the indication expires March 11, 2002; the patent expires June 15, 2001.

Although Merck is not a party to FDA's litigation with supplement marketer Pharmanex to block continued sales of Cholestin, a red yeast rice supplement, the drug company has provided extensive comments to FDA on the matter, asserting Cholestin is an unapproved new drug because of its lovastatin content. A Denver federal appeals court is scheduled to hear oral arguments in the case May 10.

One key obstacle to an OTC switch could be Mevacor's labeling requirements for liver testing before treatment initiation, at six and 12 weeks after initial therapy or dose elevation, and periodically thereafter. Current liver function test labeling requirements for HMG-CoA reductase inhibitors vary. Bristol Myers-Squibb's Pravachol (pravastatin) and Novartis' Lescol (fluvastatin) have the least stringent monitoring requirements.

Novartis previously has pointed to Lescol's safety profile as supportive of an OTC switch (³ Also see "Novartis' Lescol, Lamisil, Voltaren Emulgel mentioned as OTC switch candidates." - Pink Sheet, 23 March, 1998.). Marketing exclusivity for Lescol's current Rx indication expires Oct. 1, 2000; the drug goes off-patent in 2011. Novartis says it has not filed an NDA to switch the drug.

Pravachol received a supplemental indication in March 1998 for use in patients with normal cholesterol levels and previous myocardial infarction to reduce risk of recurrent MI, myocardial revascularization and cerebrovascular disease. Marketing exclusivity for the indication expires March 27, 2001. Pravachol's first patent expiration date is October 2005.

Pharmacia's Colestid (colestipol) also has been mentioned in the past as a possible switch candidate, and despite its failed attempt to switch Questran, Bristol previously has stated it would continue to pursue OTC status for the product.

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