Washington Editor

GAITHERSBURG, Md. - While federal advisers Thursday said anemia drugs should remain available for patients with cancer, they asked the FDA to restrict the use of those products to certain types of cancers.

In a 13-to-1 vote, the Oncologic Drugs Advisory Committee told the FDA that Amgen Inc.'s Aranesp and Ortho Biotech Products LP's Procrit should continue to be marketed to patients with cancer. But panelists voted 11 to 2, with one abstention, and 9 to 5 that the drugs, known as erythropoiesis-stimulating agents (ESAs), should no longer be indicated for patients with curable cancers and in patients with metastatic breast and head and neck cancers, respectively.

The FDA is not required to accept the recommendations of its advisory committees, but generally does so.

John Jenkins, director of the FDA's Office of New Drugs, told reporters regulators would act on the panel's recommendations as soon as possible.

Richard Pazdur, director of the FDA's Office of Oncology Drug Products, noted that the agency not only takes into account a committee's vote, but it equally weighs the advisers' discussions.

The products, along with Amgen's Epogen, are approved in the U.S. to treat anemia caused by chemotherapy in certain patients with cancer. However, under an agreement with Ortho Biotech, Amgen does not actively market Epogen for that indication.

Bridgewater, N.J.-based Ortho Biotech, a subsidiary of Johnson & Johnson, said the firm was "concerned" about the committee's recommendation to restrict access to ESAs in patients with metastatic breast and head and neck cancers and patients treated with curative intent.

"The company believes that fully informed patients and their physicians should have the choice to use this important medication, which is the only therapeutic alternative to blood transfusions," the company said in a statement.

Thousand Oaks, Calif.-based Amgen had little to say about the panel's votes, stating simply that it "takes very seriously the safety signals seen in recent trials" and was "committed to working with the FDA to consider the input from the committee and to implement future label changes."

Shares of Amgen (NASDAQ:AMGN) rose $2.19 Thursday, to close at $47.18.

Analyst Mark Schoenebaum, of Bear Stearns & Co., estimated that the use of Aranesp in patients with curable cancers with chemotherapy-induced anemia accounts for about 25 percent of the product's sales.

There is "virtually no use" in patients with head and neck cancer and use in metastatic breast cancer represents about 8 percent of Aranesp to treat chemotherapy-induced anemia, he said in a research note.

Thus, Schoenebaum predicted, new restrictions could cut fourth-quarter sales of Aranesp by about 33 percent.

Panelists reviewed data from eight studies that showed an increased risk of tumor growth and shortened survival in patients administered the drugs.

The labeling for ESAs has been revised three times in the past year, most recently last week, with stronger warnings about the risks of using the drugs in high dosages. (See BioWorld Today, March 11, 2008.)

Use of ESAs has decreased by 60 percent since last year when the FDA asked Amgen and Ortho Biotech to add a black-box warning to ESA labeling, noted Paul Eisenberg, senior vice president of global regulatory affairs and safety for Amgen.

The current black box warns about an increased risk of mortality, serious cardiovascular and thromboembolic events and tumor progression.

ESAs shortened overall survival and time-to-tumor progression in clinical studies in patients with breast, non-small-cell lung, head and neck, lymphoid and cervical cancers when dosed to target a hemoglobin of greater than 12 g/dL, the warning stated. The labeling noted that the risks of shortened survival and tumor progression have not been excluded when ESAs are dosed to target a hemoglobin of less than 12 g/dL.

Prescribers are advised to use the lowest dose needed to avoid red blood cell transfusions and to use the products only for the treatment of anemia due to concomitant myelosuppressive chemotherapy. ESAs should be discontinued following the completion of a chemotherapy course, the labeling advises.

Amgen and Ortho Biotech surprised the FDA Thursday by proposing that the labeling should be further revised to advise that the drugs be started in patients with a hemoglobin level of 10 g/dL or below.

Patricia Keegan, director of the FDA's Division of Biologic Oncology Products, told reporters that the firm had not made that proposal to regulators before Thursday's meeting. In addition, she said, a proposed risk minimization plan presented Thursday was "somewhat different" than one the firms discussed earlier with the FDA.

FDA's Pazdur asked the companies whether their suggestion to start ESAs at 10 g/dL or lower was an effort to fall in line with a decision made in July by the Centers for Medicare & Medicare Services to restrict payments for the product in patients with cancer to those whose hemoglobin levels decrease to less than 10 g/dL.

Eisenberg said his firm's proposal followed what was now recommended by European regulators for use of the drugs in patients with cancer, calling it a "conservative approach."

Amgen and Ortho Biotech argued that ESAs provide a substantial benefit in patients with chemotherapy-induced anemia.

ESAs have decreased the number of blood transfusions in patients receiving chemotherapy by about 30 percent, Eisenberg said. In the absence of ESAs, he contended, about half of patients receiving chemotherapy require transfusions, which, he said, have transient benefits and are associated with known and unknown risks.

About 85 percent of patients treated for cancer are in a community setting, where access to blood transfusions might be limited, Eisenberg added.

Panelist Wyndham Wilson, head of lymphoma therapeutics at the National Cancer Institute, noted that because of strict screening processes and new technologies, transfusions are much safer than they were when ESAs were first approved in 1993 for use in patients with cancer.

But panelist Michael Perry, director of the division of hematology and medical oncology at the University of Missouri in Columbia, argued that transfusions not only are difficult to perform but are "hazardous" because of the increased risk of lung injury and iron overload.

In addition, he said, "fewer and fewer people are choosing to donate [blood] while the population continues to rise."

Perry noted that he had received both a blood transfusion and an ESA therapy, and "if you give me the choice, I would rather have the ESA."

The panel in a 10-to-1 vote, with two abstentions, declined to back a restricted distribution program for oncology patients receiving the drugs. However, the advisers voted 8 to 5, with one abstention, in favor of mandating a written informed consent form, which should be signed by physicians and patients.

Regulators told reporters after the meeting they were perplexed by the panel's informed consent vote since the expert advisers had voted against a restricted distribution program, which is generally where an informed consent program is included.