Doctor hits FDA on Epogen oversight
He says dialysis patients at risk from anemia drug
A Boston researcher whose clinical trial linked aggressive use of anemia drugs to an increased risk of fatal heart attacks and strokes says the government is not doing enough to protect dialysis patients from the potential dangers.
Dr. Ajay Singh , clinical chief of the renal division at Brigham and Women's Hospital , oversaw a trial of the anti anemia drug Procrit in 1,432 kidney disease patients. The trial, called CHOIR , was halted last year because patients whose red blood cell counts were boosted the most died at an unexpectedly high rate. The complete study results are expected to be published this month.
In September, the Globe reported that dangerously high red blood cell levels revealed by CHOIR are found in about 65,000 of 325,000 patients treated with a nearly identical drug, Epogen, in dialysis clinics nationwide. It is part of a trend toward greater Epogen dosing by the dialysis industry. Another 160,000 patients have red blood cell levels below the danger zone demonstrated in the halted study, but still above the Food and Drug Administration's recommended limit.
Singh said the pattern of higher dosing raises safety questions that need to be addressed by the FDA, as well as the federal Medicare insurance program, which covers most dialysis treatments in the United States and pays nearly $2 billion a year for Epogen.
"If the government's not out there protecting this vulnerable population, who is?" said Singh, an associate professor at Harvard Medical School . He suggested that regulators' inaction is linked to the influence of pharmaceutical and dialysis industries, but did not cite any companies by name.
"There is lobbying going on. There's money being thrown in that is desensitizing people to what is going on," he said.
According to data gathered by the nonprofit Center for Responsive Politics , which tracks lobbying expenditures, Amgen spent $5.7 million lobbying Congress and federal agencies in 2005. DaVita Inc., the nation's second-largest for-profit dialysis chain, spent $380,000, and Fresenius Medical Care , the largest dialysis chain, spent $160,000. Kidney Care Partners , an industry group, spent $1 million, according to the center.
In anticipation of the CHOIR study's publication, physicians and policy specialists are debating a basic question: How much Epogen is too much? Even though the drug is widely used to manage anemia in all kidney patients -- not just the 325,000 on regular dialysis -- as well as in cancer patients undergoing chemotherapy, definitive studies on its effectiveness and safety thresholds have not been performed.
Singh said the FDA should require Amgen and other manufacturers of the drugs -- synthetic hormones which stimulate red blood cell production in bone marrow -- to sponsor studies to establish a threshold for anemia treatment.
"They can't abdicate this responsibility. They need to take it on," he said.
Before Amgen introduced Epogen in 1989, dialysis patients required blood transfusions to combat anemia. Amgen said it has never promoted use of the drug beyond FDA recommendations. The company said data showing patients with high red blood cell counts reflects temporary fluctuations, not longer-term dosing. In a written response to questions from the Globe, the Thousand Oaks, Calif., company said, "We are confident that over its 17-year history, Epogen has improved the quality of life for 1.4 million patients and provided meaningful clinical benefits in this vulnerable population when used in accordance with the FDA-approved product label."
The FDA has said physicians and clinic staff should not push red blood cell counts above the agency's recommended limit. This week it said it is working on ways to get the message out that the label should be strictly observed.
Critics say dialysis clinics have an incentive to increase Epogen doses because federal law guarantees them at least 6 percent profit on every dose.
Days before the CHOIR trial results were publicly summarized at an April scientific meeting, Medicare loosened its guidelines to allow for larger Epogen doses, saying a more flexible policy was needed because individual patients react differently to the treatment. The FDA-approved label for the drug recommends a limit of 12 grams of red blood cells per deciliter of blood, but Medicare now permits up to 13 grams.
A National Kidney Foundation panel this year also issued practice guidelines that said red blood cell counts of up to 13 grams are desirable. The panel, which conducted its research with grant money from Amgen, reviewed available clinical studies and statistical information. But it noted that the guidelines were not based on rigorous clinical trial evidence, the gold standard for pharmaceutical safety and effectiveness.
"The question is: How do you translate what the FDA asks for into practice?" said the panel's chairman, Dr. David Van Wyck , a physician and researcher at the University of Arizona College of Medicine in Tucson. "The FDA isn't even clear about that."
The CHOIR trial evidence was not included in the panel's deliberations because the study's results had not been published in an academic medical journal, Van Wyck said.
Christopher Rowland can be reached at crowland@globe.com. 