U.S. FDA staff questions Glaxo kidney cancer drug

WASHINGTON (Reuters) - The U.S. Food and Drug Administration's review staff expressed doubts that GlaxoSmithKline Plc's experimental kidney cancer drug Votrient should be approved given concerns about liver injury, documents released on Thursday said.

Votrient, also known by its chemical name pazopanib, aims to treat advanced renal cell carcinoma. But while the company's data showed a five-month improvement in median progression-free survival, the FDA reviewers saw no "statistically significant improvement" in overall survival.

"FDA is concerned about the benefit-to-risk ratio of pazopanib in the intended population of patients. This is particularly true in a setting in which there are other effective products approved for the treatment of advanced renal cell cancer," the staffers wrote.

If approved, it would be the sixth medication on the U.S. market to treat the disease.

Other renal cell cancer drugs include Pfizer's Sutent, Roche unit Genentech's Avastin, Wyeth's Torisel, Novartis AG's Afinitor, and Onyx Pharmaceuticals Inc and Bayer AG's Nexavar.

At an FDA advisory panel meeting on Monday, Glaxo officials will make their case for approval. The FDA, which released the memo ahead of the meeting, usually follows its advisers' recommendations, but is not bound by them.

Glaxo, in a separate document also released on Thursday, said Votrient was effective. It noted that all similar renal cell drugs can be toxic and that Votrient's side effects were manageable.

"Pazopanib represents a valuable option for the treatment of patients with this disease," it said.

But FDA staff pointed to a number of safety concerns.

In particular, there were higher liver enzyme, or ALT, levels in patients given Votrient compared with placebo, they said. Three liver-related deaths associated with the drug also "strongly suggest" it could cause a significant increase in severe liver injury if it was approved for use, they added.

Votrient is a type of renal cancer drug that targets a vascular endothelial growth factor (VEGF) receptor and aims to limit new blood vessels that can feed tumors.

Such drugs, including Votrient, are known to cause high blood pressure, blood clots and perforations of the stomach or intestines, among other side effects, the FDA said. Pfizer and Bayer's drugs are also VEGF inhibitors.

To conduct its trial, Glaxo went outside the United States to countries without approved advanced renal cell cancer drugs. It is currently conducting a study comparing Votrient to Pfizer's drug, which has become the standard U.S. treatment, the company said.

Glaxo has said it expects the FDA to make its approval decision by October 19.

The FDA released the memo on its website here

(Reporting by Susan Heavey, editing by Gerald E. McCormick and Maureen Bavdek)