FDA questions on long term benefits of Orlistat
Jan 21, 2006 - 5:12:37 PM

Efficacy concerns surrounding GlaxoSmithKline's orlistat may prove to be a bigger hurdle to overcome than safety or self-selection issues as the firm pursues an Rx-to-OTC switch of the drug.

Although the proposed OTC dose of 60 mg shows statistically significant weight loss, 'there is no evi­dence presented that a modest, transient weight loss due to orlistat will afford any long-term clinical benefit through either a change in behavior or a reduced risk of serious clinical diseases manifested by being over­weight,' an FDA review of studies on the drug finds.

The FDA documents, released Jan. 20, question whether GSK's proposed six-month treatment submitted under the trade name Alli would be beneficial for a 'chronic' condition such as obesity.

The documents were released in advance of a Jan. 23 review of the switch proposal by the agency's Nonprescription Drugs and Endocrinologic & Metabolic Drugs advisory committees.

GSK filed the orlistat switch application in June after purchasing licensing rights to the drug's OTC version from Roche in July 2004.

According to the agency, drug treatment for chronic conditions 'must be maintained long-term or chronically' to result in clinical benefit.

"It is difficult to define the clinical benefits of short-term treatment with orlistat," FDA states.

"Although not studied by the sponsor, it is well known that once weight-loss treatment is stopped, lost weight is quickly regained and improvements in co-morbidities become undone."

Efficacy of orlistat use in �mildly overweight� people with a Body Mass Index of 25-28 also was questioned in the agency's review.

Comparing studies conducted for orlistat's Rx approval and proposed switch "raise[s] the possibility that orlistat may be less effective in mildly overweight individuals than in obese subjects," the agency states.

The prescription NDA study was conducted in people with a BMI of at least 28. Among the subjects, a 5% or greater weight loss was achieved by 42% of those who took a 60 mg dose, 45% of subjects who took a 120 mg dose and 23% of those taking placebo.

In a more recent study conducted to support an orlistat switch, participants had a BMI of 25-28. A 5% or more weight loss was achieved in 36% of those taking the 60 mg dose and 28% taking placebo.

The difficulty in determining the benefits of short-term treatment is "further complicated," the agency states, because "some evidence suggests that the overweight BMI range of 25- <30 is not associated with increased mortality

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