New FDA Authority Tested With Amgen Anemia Drugs

Washington, DCA new law that gives the US Food and Drug Administration (FDA) the authority to mandate changes to a drug's labeling, has just been tested with Amgen's flagship anemia drugs.

In the past, the FDA always negotiated changes to a drug's labeling in concert with the drug manufacturer—a practice it maintains to this day. However, should the two camps not agree on specific wording, or not agree to a change at all, the FDA now has the authority to mandate a change on its own.

That authority is tied to a law passed in Congress last year, and was tested for the first time after negotiating with Amgen and Johnson & Johnson with regard to Aransep and Procrit, two anemia drugs that have seen sales plummet over the last year after studies suggested that their use to fight the anemia caused by chemotherapy in cancer patients could actually make the cancer worse, and effectively shorten lives.

Even though the labels were changed more than once last year due to emerging safety concerns, an FDA advisory committee recommended in March that use of the drugs should be restricted further. Following negotiations, the FDA and the manufacturer could not agree on the final language of the labeling update, although there was agreement on most points. Once the stalemate appeared, the FDA invoked its newfound authority to order the final changes it wanted.

Aransep, considered by most as Amgen's flagship product, is also used by patients suffering from kidney disease. However, the concern has to do with the use of Aransep and its sister product, Procrit, with cancer patients suffering anemia during, or following chemotherapy.

At issue is prior language that allegedly implied that the drugs were safe to use until a patient's hemoglobin rose to 12 grams per deciliter. In actual fact, according to Dr. Richard Pazdur of the FDA's oncology drug office, safety is— more correctly, unknown.

The label change removes that implication, and revises the hemoglobin count to 10. In other words, use of the drugs should not begin until a patient's hemoglobin level drops to 10 grams per deciliter.

Anemia drugs have proven useful to combat the fatigue experienced by patients suffering from anemia, a condition worsened further due to the rigors of chemotherapy required by cancer patients. While the anemia drugs appeared to effectively combat fatigue, it also appears to worsen the cancer itself, and there are no accepted theories as to why that is.

The new label goes further, suggesting that the drugs should not be used if chemotherapy is being used in an attempt to actually cure a patient, rather than to simply extend the patient's life. For example, sometimes chemotherapy is used as adjuvant therapy, following the successful removal of a cancerous tumor. The chemotherapy, in this case, is used almost as a failsafe, in an attempt to ward against the cancer coming back.

When cancer is advanced, chemotherapy is not considered curative, but is used in an attempt to slow its progression. In such an instance the anemia drugs, according to the FDA, should not be used.

It should be noted that the FDA did concede one point recommended by its own advisory panel. The latter recommended that Aransep and Procrit not be used for all types of breast cancer, or head and neck cancers, given that the risks associated with the drugs appeared to be stronger for those particular forms of cancer. However, the FDA conceded that point, and will leave it to the discretion of doctors.

Aransep and Procrit are both manufactured by Amgen, but Procrit is sold under license by Johnson & Johnson. Both companies indicate they will co-operate fully with the FDA and abide by the agency's stated restrictions. Sales of both drugs have fallen dramatically over the year, and are expected to dip further as a result of the new labeling. However, it has been reported that Amgen factored in the expected drop in sales fuelled by the label change into its financial guidance, which it provided to investors July 28th.

It should be noted that the label change might make it tougher for Amgen to persuade Medicare to loosen its policy with regard to paying for use of the drugs in patients with hemoglobin levels above 10 grams per deciliter. Currently, Medicare protocol provides that it will not allow reimbursement for any anemia drug used in a patient whose hemoglobin count is above 10. The manufacturer, together with many oncologists, had been arguing that the drug labeling suggested that the FDA supported use up to, and including a 12 count as being safe.

The new change removes any reference to a 12 count. Amgen wanted the 12 count upper limit to remain, and also wanted doctors to have the discretion to start the drugs in patients whose hemoglobin count had not yet dropped to 10, but could not tolerate that degree of anemia.

The FDA took an opposing view, and thanks to its new powers, got its way.