FDA Abandons ESA Target Range, Lowers Dosing Recommendations

The U.S. Food and Drug Administration (FDA) recently recommended more conservative dosing guidelines for erythropoiesis-stimulating agents (ESAs) used to treat anemia in patients with chronic kidney disease (CKD), for both patients receiving dialysis and those not receiving dialysis. Before the FDA’s announcement on June 24, 2011, product labels for ESAs recommended dosing to achieve and maintain hemoglobin levels within the target range of 10–12 g/dL in patients with CKD.

The modified guidelines remove the concept of a target hemoglobin range and instead now recommend that “Physicians and their patients with chronic kidney disease should weigh the possible benefits of using ESAs to decrease the need for red blood cell transfusions against the increased risks for serious adverse cardiovascular events. For each patient, individualize dosing and use the lowest dose of ESA sufficient to reduce the need for transfusion.”

For patients with the anemia of CKD who are not receiving dialysis, the FDA now recommends that physicians consider starting ESA treatment only when the hemoglobin level is less than 10 g/dL and when certain other considerations apply, and that if the hemoglobin level exceeds 10 g/dL, the dosage of ESA should be reduced or interrupted.

The FDA also now recommends that for patients with the anemia of CKD who are receiving dialysis, physicians begin ESA treatment when the hemoglobin level is less than 10 g/dL. If the hemoglobin level approaches or exceeds 11 g/dL, the dosage of ESA should be reduced or interrupted.

“Health care practitioners should carefully consider when to begin treatment with an ESA and actively monitor dosing in patients with chronic kidney disease, keeping in mind the increased risk for serious cardiovascular events, and should talk to their patients about these potential risks,” said John Jenkins, MD, director of the office of new drugs in the FDA’s Center for Drug Evaluation and Research. “The goal is to individualize therapy and use the lowest ESA dose possible to reduce the need for red blood cell transfusions.”

The FDA cited data from clinical trials, including TREAT (Trial to Reduce Cardiovascular Events with Aranesp Therapy), as the basis for guideline changes, stating that “TREAT showed using ESAs to target a hemoglobin level of greater than 11 g/dL increased the risk of serious adverse cardiovascular events, such as heart attack and stroke, and provided no additional benefit to patients.” The use of ESAs to treat anemia in patients with CKD was most recently discussed at the Cardiovascular and Renal Drugs Advisory Committee meeting in October 2010. ASN public policy board member Wolfgang Winkelmayer, MD, ScD, FASN, presented testimony on behalf of the society at that meeting.

Besides changing the labels and recommendations for ESAs, the FDA is also requiring Amgen, the manufacturer of Epogen, to conduct at least two new clinical trials of its product. One trial should identify the optimal ESA dosage and schedule strategy in patients with CKD who are receiving dialysis, and the other should determine whether a fixed dosage strategy different from what the currently approved label recommends can further reduce exposure to ESA while preserving the benefit of reducing transfusion use in patients with CKD who are not receiving dialysis.

“Though the long-term effects of the new FDA recommendations are as of yet unclear, I see some potential pros and cons,” said ASN public policy board chair Thomas Hostetter, MD. “I think it’s heartening that the FDA has so emphasized individualizing patient care. Yet, as always, we remain deeply concerned about protecting patients’ access to ESAs in order avoid blood transfusions and maintain a high quality of life.”

August 2011 (Vol. 3, Number 8)