Alli Sparks Reevaluation Of OTC Weight-Loss Indication

Understanding of obesity, weight loss has “evolved,” since the OTC weight loss monograph was established more than two decades ago, FDA’s Office of Nonprescription Products says.

FDA will revisit its thinking about weight loss as an OTC indication as the agency decides whether to allow Xenical to be sold without a prescription.

Currently, weight loss in and of itself is an approvable OTC indication, and it is under this indication that GlaxoSmithKline is sponsoring an Rx-to-OTC switch of Xenical, which would be marketed over-the-counter as Alli .

"We think it is clear that the science and thinking has evolved" since the proposed monograph for weight control drugs was established in 1982, FDA's Office of Nonprescription Products said. "We would have to take that into consideration in evaluating therapies."

The Nonprescription Drugs and Endocrinologic & Metabolic Drugs advisory committees voted in favor of the switch Jan. 23 but struggled with the "cosmetic" nature of the indication, at times pointing out that the Rx guideline requires prescription weight-loss drugs to show clinical benefit.

An FDA review of the drug prior to the meeting also expressed concern that the drug would not provide any long-term clinical benefit and pointed out that obesity is now understood to be a chronic condition requiring long-term treatment.

If Alli (orlistat 60 mg) were approved for the current OTC indication, it would be a substantially different indication than that of Rx Xenical (orlistat 120 mg).

However, NDAC Chair Alastair Wood, Vanderbilt University School of Medicine, compared the weight-loss indication to that of laxatives or Rx erectile dysfunction drugs.

In both cases, the drug essentially either works or does not work, and the drugs do not have to demonstrate clinical benefit such as reduction in mortality or morbidity.

If a sponsor comes to an advisory committee "with an approvable indication such as athlete's foot…we don't necessarily have to demonstrate this long term ability or mortality benefit," he said.

However, many committee members still added caveats about a lack of long-term benefit to their affirmative vote. Other members, including Wood, also said that a decreased use of dietary supplements could be a potential benefit of having an FDA-approved OTC on the market.

The expressed desire for Alli to have a benefit beyond short-term weight loss hints that the laxative and athlete's foot analogy does not sit comfortably with panelists.

However, Wood questioned what he saw as the committee's assumption that a drug "should not be used for cosmetic weight loss," such as losing weight for a college reunion.

The drug has a good safety profile, he noted.

Cosmetic weight-loss would put OTC orlistat in the realm of "lifestyle enhancement" drugs like Pfizer's Viagra , noted Eric Colman, Division of Metabolism & Endocrinology Products. "It is safe to say that if I were a reviewer for [Viagra], I would have recommended non-approval," he asserted.

"You have to look at the individual drug, but this is a general principle: you don't go to drugs right off the bat, and you try to target higher risk patients with the drug," Colman added.

"It seems to me that the question that GSK is here asking is for over-the-counter use for a drug to produce weight loss - just weight loss," Wood stated. "Rightly or wrongly, that's an approvable indication."

ONP says that revisiting the proposed OTC monograph for weight control drugs is "not one of our priorities right now."

Recommendations regarding the monograph could come in the form of a proposed rule, the office said.

Changes to the monograph would not "necessitate another advisory review panel," but "if we wanted an advisory group to look at it we could bring the issue before NDAC with additional [special government employee] experts," ONP stated.

- Katia Fowler