FDA panel votes against wider use of Amgen drug

An advisory panel on Wednesday recommended that U.S. health regulators reject the use of Amgen Inc's drug Xgeva to delay the spread of prostate cancer to the bone, dimming the chance of a wider use for one of the company's key growth drivers.

The outside advisers to the Food and Drug Administration voted 12-to-1 that the benefits of the injectable drug, known chemically as denosumab, did not outweigh the risk of developing a jawbone-destroying condition.

Xgeva is already approved to prevent fractures and related problems in advanced prostate cancer that has spread to the bone, and the company is seeking additional approval for use of the drug to delay or prevent the spread.

The drug did delay the spread of cancer to the bone by a little longer than four months in a clinical trial of 1,432 men with prostate cancer who had stopped responding to hormone therapy.

But about one in 15 men who took the drug developed osteonecrosis of the jaw, a severe side effect in which jawbone tissue dies, exposing the bone. That rate is far higher than has been seen with widely used osteoporosis drugs.

"If you ask a patient, 'Do you want to delay your disease by five minutes, but get significant toxicities?' I think that would give them pause," said panel member Maha Hussain, a professor of medicine in the hematology and oncology division at the University of Michigan.

The FDA usually follows the recommendations of its expert panels and will make a final decision by April 26.

Most analysts had expected the unfavorable panel vote because the FDA had questioned whether delaying the spread of cancer to the bone was a meaningful benefit to patients given that the drug did not help men live longer or delay the growth of prostate cancer..

"We believe the panel recommendation reinforces the FDA's view, which has been consistently negative, and approval is unlikely," said Geoff Meacham, analyst at JP Morgan, in a research note.

However, he said the risk of a rejection of wider approval for Xgeva had only a modest risk to his long-term revenue estimates for Amgen, the world's largest biotechnology company.

Benefits to patients?

Xgeva and a related osteoporosis drug Prolia are seen as among the most important growth drivers for Amgen and are expected to help offset declining sales of the anemia drugs that had been the company's backbone.

In the fourth quarter of 2011, sales of Xgeva rose to $134 million from $100 million in the prior quarter, and it is expected to eventually become a $1 billion-a-year drug.

The company said the new use for Xgeva would be targeted at about 50,000 men in the United States at that advanced stage of the disease.

Panel members questioned whether using the drug earlier actually benefited patients, as many did not have symptoms of the disease, but would suffer any drug-related side effects.

However, the patient representative on the panel voted in favor of approval.

"There isn't a treatment that a man with prostate cancer gets that doesn't have devastating effects on his masculinity and his quality of life," said James Kiefert, of Olympia, Washington. "In my opinion, the men who would be candidates for this treatment would be standing up and cheering another option for them."

His views echoed the favorable comments of several urologists, who testified in favor of the drug during the public hearing.

Amgen said Xgeva provided a meaningful benefit to prostate cancer patients by preventing the spread of their disease to the bones, which is not uncommon.

"We look forward to further discussions with the FDA as they continue to review our application," the company said in a statement after the vote.

If Xgeva gains wider approval, it would be the first drug to delay the spread of prostate cancer to the bone, Amgen said.

Amgen said it was also testing Xgeva in other cancers, including breast and lung cancer and the blood cancer multiple myeloma.