Xenical Should Be Pulled From Market Due To Possible Precancer Ties, Public Citizen Says

A petition from the advocacy group comes days after GSK receives an “approvable” letter for the obesity drug’s Rx-to-OTC switch.

Public Citizen is calling for the withdrawal of Roche's prescription obesity drug Xenical (orlistat) just days after FDA sent an "approvable" letter to GlaxoSmithKline for an OTC version of the drug.

GSK said that it had received an approvable letter April 6 for its over-the-counter switch application for orlistat, which the firm would market as Alli . At a meeting of FDA's Nonprescription and Endocrinologic & Metabolic Drugs advisory committees in January, committee members voted to recommend approval of the switch but discussed the need for more actual-use clinical data (¹ (Also see "Glaxo's Alli Favored For OTC Weight-Loss Use By FDA Joint Panel" - Pink Sheet, 23 Jan, 2006.)).

However, while FDA appears to be moving toward approval of the Rx-to-OTC switch, Public Citizen asserts that orlistat "has been known to cause a significant increase in aberrant crypt foci (ACF), which are widely believed to be a precursor to colon cancer."

In an April 10 ² petition addressed to FDA Acting Commissioner Andrew von Eschenbach, Public Citizen urges FDA to remove prescription Xenical from the market and says that the ACF relationship "makes it even clearer how ill-advised switching orlistat to OTC status would be."

The advocacy group uses data from rat models that demonstrate that "both a high-fat diet and orlistat (which by itself increases the excretion of fat) increased ACF formation."

According to the petition, human data demonstrates "a correlation between the stage of colon cancer and the relative risk of having an advanced form of ACF, i.e., those with colon cancer had a 30% increased risk of having nondysplastic ACF and an 18-fold greater risk of having dysplastic aberrant foci (foci further along the path toward colon cancer) compared to those people without colon cancer."

Public Citizen also notes that FDA's review of Xenical, which was approved in 1999, had evaluated whether there is an increased risk of breast cancer associated with orlistat. As a condition of approval, the agency requested monthly updates about breast cancer diagnoses in orlistat users.

However, Roche asserted that an increase in breast cancer cases seen in clinical trials was coincidental rather than causal.

Current labeling for Xenical does not refer to increased risk of ACF, colon cancer or breast cancer.

Labeling for Xenical refers to two studies of up to six weeks duration that reported no statistically significant changes in colonic cell proliferation rate.

In the petition, Public Citizen appeals to von Eschenbach's role as director of the National Cancer Institute, noting that "you have repeatedly talked about preventing death and suffering from cancer."

"The failure to ban the prescription version of this drug, or, worse, to make it much more widely available by allowing OTC sales, is a decision that is likely to increase cancer incidence."

-Kathleen Michael