From: WSJ

The Food and Drug Administration said a proposed GlaxoSmithKline PLC cancer drug was associated with a risk of severe liver injury and questioned whether the drug should be approved.

Glaxo is seeking FDA approval of the drug, pazopanib, to treat patients with advanced kidney cancer. It faces a review by an outside panel of medical experts who serve on the agency's oncologic drugs advisory committee.

The FDA posted a review of the pazopanib on its Web site Thursday in advance of the panel meeting on Monday.

Pazopanib, a tablet taken orally, works by attacking a protein involved with cancer tumor growth and blood vessels that help tumors grow. It falls into the same class of other targeted cancer drugs approved for use in kidney cancer like Pfizer Inc.'s Sutent and Nexavar, marketed by Bayer Pharmaceuticals Corp. and Onyx Pharmaceuticals Inc.

The FDA said there were three deaths seen in clinical trials of pazopanib from liver injury that were "related to or associated with pazopanib." The agency said the "findings strongly suggest that pazopanib may be associated with a significant risk of severe idiosyncratic hepatic injury if used in a larger population."

The agency said it was concerned about the benefit-to-risk ratio of pazopanib, particularly "in a setting in which there are other effective products approved for the treatment of advanced [kidney] cancer."

The FDA has approved five kidney cancer treatments since December 2005 including Sutent and Nexavar.

GlaxoSmithKline, in a document also posted to FDA's Web site, said the toxicity of chronic therapy to treat advanced kidney cancer "is an important challenge" and that there are differences in the safety profiles of all the drugs "making some therapies less tolerable than others for individual subjects." The company said pazopanib would be a "valuable treatment option" to treat advanced kidney cancer.

The FDA said there's been a "few" cases of liver failure associated with Sutent and Nexavar reported in medical literature, which may be "suggestive of a class effect." But the agency said neither drug showed a significant liver-safety problem during pre-marketing clinical studies.

The agency said the effectiveness of pazopanib at treating kidney cancer appears to be similar to Sutent and Nexavar. The agency said "exposure of patients to the risk of severe and fatal hepatoxicity to pazopanib is problematic" given that there are other treatments for the disease.