Rafel Dwaine Rieves, MD Acting Director Division of Medical Imaging and Hematology Products Center for Drug Evaluation and Research Food and Drug Administration 5600 Fishers Lane Rockville, MD 20857 Re: Recommendations and Comments of the Cardiovascular and Renal Drugs Advisory Committee and the Drug Safety and Risk Management Advisory Committee on Erythropoiesis-Stimulating Agents Dear Dr. Rieves, On September 11, 2007, the Cardiovascular and Renal Drugs Advisory Committee (CRDAC) and the Drug Safety and Risk Management Advisory Committee (DSRMAC) held a joint meeting to discuss updated information on the benefits and risks of erythropoiesis-stimulating agents (ESA) used for the treatment of anemia due to chronic renal failure. Kidney Care Partners (KCP), a coalition of members of the entire kidney care community, strongly encourages you to follow the recommendations and comments made by the Advisory Committees for purposes of determining the appropriate hemoglobin range and consideration for retention of quality of life claims. We also would like the FDA to clarify how it is interpreting the vote on question 4 regarding dosing guidance derived from the Normal Hematocrit Study and the CHOIR study as it appeared there was some confusion about this question. We are supportive of the outcomes of the September 11th FDA advisory board. The only clarification we seek is the FDAs interpretation of the vote on question 4 posed at the meeting on the use of the Normal Hematocrit Study and CHOIR to support ESA dosage recommendations. We believe that it would be inappropriate for FDA to rely upon the Normal Hematocrit Study and CHOIR to support ESA dosage recommendations. Both the Normal Hematocrit Study and CHOIR were off label with regard to target hemoglobin and dosing regimen and should not be the basis of dosing recommendations. Neither study was designed to address the question of optimal ESA dosing. We believe that the Advisory Committees vote on this issue appeared to be confused and, therefore, should not be followed. KCP applauds the Advisory Committees recommendation to reaffirm ESA dosing practices with the institution of a target. It is the kidney care communitys belief, as presented in the public session, that the optimal hemoglobin target is 11-12 g/dL. Panel members overwhelmingly voted (14 to 5) against changing ESA product labels to state that the target hemoglobin should not exceed approximately 11 g/dL for both patients on kidney dialysis and patients with advanced kidney disease who are not on dialysis. The kidney care community supports this decision because we recognize that if the target were lowered to 11 g/dL, more patients would be at risk of requiring blood transfusions. Patients, physicians, and facilities alike believe that blood transfusions should be minimized, because (1) transfusions can result in serious risks to patients and (2) these risks can exceed those known risks associated with the use of ESAs. The label should be clarified to ensure that patients are not forced to undergo unnecessary and risky blood transfusions. We also support the Advisory Committees conclusion that not only would it be too restrictive to set a hemoglobin target not to exceed approximately 11g/dL, but also that there is no evidence to demonstrate that the upper end of the target range at 12 g/dL is unsafe. These findings are consistent with the recently published, and scientifically based, guidelines of the National Kidney Foundation Kidney Disease Outcomes Quality Initiative (KDOQI). After an extensive review of the results of six new studies, the KDOQI workgroup updated its Clinical Practice Guideline on Anemia to recommend that ESA therapy in dialysis and non-dialysis CKD patients should target hemoglobin levels in the range of 11 to 12 g/dL. KCP strongly encourages the FDA to follow the recommendation of the Advisory Committees and avoid limiting the upper threshold of hemoglobin levels to 11 g/dL. Additionally, we are concerned about the complete removal of quality of life language from the Epoetin alfa label. The members of both Advisory Committees acknowledged that patient quality of life issues are an important part of the discussion on the risks and benefits of ESAs. As was discussed during the public session, before the availability of ESA treatment for anemia, most dialysis patients experienced a severely impaired quality of life as a result of their physical and mental fatigue. Since the advent of ESAs, published reports measuring their impact on patient quality of life have demonstrated improvements in physical functioning, daily activities, cognitive function, and anemia symptoms, including energy, weakness and shortness of breath. It is imperative that such benefits be carefully balanced with the labeled risks by providers as they treat anemia in kidney patients. Although we understand that the FDA has recently established draft guidance with regard to the methods used to obtain patient reported outcomes (PRO) claims in labels, it is not clear that these guidelines were written to be applied retrospectively. We agree with other organizations, such as BIO, that there may be potential legal and policy considerations that counsel against the retroactive application of these draft guidances. While new quality of life studies may be conducted in the future using the final FDA guidance on PROs, we believe it is inappropriate to disregard the original studies that were conducted that lead the FDA to include PROs on the Epoetin alfa label. In addition, KCP agrees with the Advisory Committees comments suggesting that additional attention should be focused on defining, identifying, and treating patients who are hyporesponders to ESAs. KCP encourages the conduct of studies and the development of industry consensus on issues related to hypo-responsive patients. The September 11, 2007 meeting of the Advisory Committees on ESAs underscores the complexities of ESA dosing and other issues associated with anemia treatment in patients suffering from chronic kidney disease. KCP appreciates the Advisory Committees thoughtful review and discussion of these issues as well as FDAs consideration of all relevant public comments. If you have any additional questions or need additional information, please do not hesitate to contact Kathy Lester at 202.457.6562. Sincerely, Edward R. Jones, MD Chairman Kidney Care Partners: Abbott Laboratories AMAG Pharmaceuticals American Kidney Fund American Nephrology Nurses Association American Regent, Inc. American Renal Associates, Inc. American Society of Nephrology American Society of Pediatric Nephrology Board of Nephrology Examiners Nursing and Technicians California Dialysis Council Centers for Dialysis Care DaVita, Inc. DaVita Patient Citizens DSI Fresenius Medical Care North America Fresenius Medical Care Products and Hospital Group Genzyme Kidney Care Council National Association of Nephrology Technicians and Technologists National Kidney Foundation National Renal Administrators Association National Renal Alliance, LLC Northwest Kidney Centers Renal Advantage Inc. Renal Physicians Association Renal Support Network Renal Ventures Management, LLC Roche Satellite Healthcare U.S. Renal Care Watson Pharma, Inc.  KCP is a coalition of members of the kidney care community, including renal patient advocates, dialysis care professionals, providers, and suppliers who collaborate to improve the quality of care for chronic kidney disease (CKD) patients with irreversible kidney failure, also known as end stage renal disease (ESRD).