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FDA Documents Question Safety Of Anemia Medications In Advance Of Meeting

September 09, 2017

FDA on Tuesday posted documents on its Web site questioning the safety of higher doses of anemia drugs manufactured by Amgen and Johnson & Johnson that are used by chemotherapy and kidney failure patients, the Wall Street Journal reports. FDA released the documents in advance of an advisory panel meeting scheduled for Thursday that will consider whether the labels for Amgen's Aranesp and Epogen and J&J's Procrit require new warnings for cancer patients (Loftus, Wall Street Journal, 5/9).

FDA in March issued a black box warning for the drugs -- known collectively as erythropoietin drugs -- to warn doctors that they should use only the lowest dose necessary to avoid the need for blood transfusions. FDA's warning pertains to the use of EPO drugs to raise anemia patients' hemoglobin levels to more than 12 grams per deciliter of blood, the lowest hemoglobin level considered non-anemic (Kaiser Daily Health Policy Report, 3/15).

FDA in the documents released on Tuesday said, "Further modifications to product labeling may be appropriate to minimize risks to patients, through restrictions of the indicated patient population or further limitations on dosing to achieve the minimal hemoglobin level necessary to avoid transfusions." FDA said clinical studies have shown EPO drugs prescribed in certain ways to cancer patients can increase the risk of death, cardiovascular disease and tumor growth. Five randomized clinical trials demonstrated that cancer patients who received EPO drugs had decreased survival times compared with patients who received blood transfusions, FDA said.

Moreover, three randomized clinical trials found that tumor outcomes for patients taking EPO drugs were inferior to the outcomes of patients who received transfusions, according to FDA. Most of the studies targeted higher-than-recommended hemoglobin levels, FDA said.

Reaction
Amgen in documents submitted to FDA in advance of Thursday's meeting said that the findings of studies assuming a "negative impact on tumor progression and survival in cancer patients" were "questionable" (Wall Street Journal, 5/9). Eric Schmidt, an analyst at Cowen & Co., said, "There are more questions than answers right now. But if I'm reading the tea leaves, I would say the companies shouldn't be waiting for positive news." Schmidt added that EPO drug sales are predicted to fall by about 20% this year and that additional restrictions might reduce sales by an additional 20% (Costello, Los Angeles Times, 5/9).

Physician Payments
The New York Times on Wednesday examined how Amgen and J&J pay "hundreds of millions of dollars to doctors every year" to treat patients with EPO drugs. Federal law prohibits pharmaceutical companies from paying doctors to prescribe medicines that are given in pill form and purchased by patients at pharmacies, but companies can rebate part of the price to doctors who purchase treatments that are administered in their offices. Anemia drugs are injected or delivered intravenously in doctors' offices or dialysis centers. Physicians receive rebates after they buy the drugs from the companies. Rebates generally are higher for physicians who agree to use one company's EPO drugs exclusively. Doctors also receive reimbursements from Medicare or private insurance companies for the drugs, often at a markup more than the purchase price.

Neither Amgen nor J&J has disclosed the total sum of their payments to physicians, but the Times was given documents showing that one medical practice in the Pacific Northwest employing six cancer physicians received $2.7 million from Amgen in 2006 for administering $9 million worth of its EPO drugs. According to the Times, "very few people outside of the doctors who receive them are aware" of the size of the payments, and some cancer and kidney doctors argue that the payments "give physicians an incentive to prescribe the medicines at levels that might increase patients' risks of heart attacks or strokes."

Dialysis patients in the U.S. receive doses of EPO drugs more than twice as high as patients in Europe. U.S. cancer patients are three times as likely as European patients to receive the drugs, which they receive at somewhat higher doses. Ajay Singh -- an associate professor at Harvard Medical School who led a clinical trial that reported last year that the drugs might be unsafe in kidney patients at commonly prescribed doses -- said that the companies have a "burden of proof" to show that the drugs are safe at prescribed levels. Amgen and J&J said that rebates are a normal component of market competition (Berenson/Pollack, New York Times, 5/9).

"Reprinted with permission from kaisernetwork. You can view the entire Kaiser Daily Health Policy Report, search the archives, or sign up for email delivery at kaisernetwork/dailyreports/healthpolicy. The Kaiser Daily Health Policy Report is published for kaisernetwork, a free service of The Henry J. Kaiser Family Foundation . © 2005 Advisory Board Company and Kaiser Family Foundation. All rights reserved.