Reacting to a February 2007 FDA safety alert on the off-label use of erythropoietic stimulating agents (ESAs), Noridian Administrative Services (Noridian), a Medicare Administrative Contractor for 13 states in the west and midwest, announced that, effective March 5, 2007, Medicare will deny payment for the off-label use of darbepoetin alpha (ARANESP or DPA). Other Medicare contractors are likely to follow Noridian’s lead in the coming weeks. Three ESAs –ARANESP, EPOGEN, and PROCRIT– are FDA approved to treat anemia in patients with chronic kidney failure and cancer patients undergoing chemotherapy. However, these drugs are also used off-label to treat anemia and fatigue in surgical patients and patients with HIV. Noridian’s revised Local Coverage Decision (LCD) revoking payment for ARANESP noted several important developments. FDA’s February 16, 2007 alert states that “ESAs are not FDA approved to treat anemia in cancer patients not receiving chemotherapy.” The United States Pharmacopeia-Drug Information (USP-DI), a Medicare-recognized drug compendium, described the treatment of cancer-related anemia with DPA as “unaccepted.” Additionally, Amgen, the manufacturer of ARANESP, recently issued a letter to health professionals stating that DPA “should be used only in accordance with its approved product labeling.” Amgen issued the letter after observing increased mortality in patients treated with DPA for cancer-related anemia.
Noridian’s policy revision is noteworthy and may be used by other contractors to revoke payment for ARANESP and other ESAs. The Medicare contractor used a provision in the Medicare Program Integrity Manual (PIM) to revise its LCD on ARANESP without notice and comment. Chapter 13, section 13.7.3 of the PIM allows Medicare contractors to revise coverage policy immediately when there are safety concerns about a product or procedure. Based on the safety concerns raised by FDA’s alert combined with the actions of the USP-DI and Amgen, Noridian decided that sufficient safety concerns existed to immediately revoke Medicare payment for the off-label use of ARAESP. However, the revised policy does not affect ARAESP used on-label to treat anemia caused by chemotherapy. Noridian also plans to review Medicare coverage of ESAs in the coming weeks and requests public comment and peer-reviewed literature on their use. FDA, on March 9, 2007, approved a "black box" warning and other labeling revisions for both DPA and epoetin alpha (EPOGEN/PROCRIT). CMS, on March 14, 2007, announced that it will review the use of ESAs in all non-end-stage renal disease applications. CMS also took a step toward generating a National Coverage Decision (NCD) by opening a National Coverage Analysis (NCA) with a 30-day public comment period on ESAs in all non-renal applications. CMS will use the NCA to analyze clinical studies, medical literature and other medical evidence submitted in public comments to determine whether the agency’s coverage and reimbursement policies on ESAs should be revised.
Considering Medicare’s heightened review and recent FDA action, manufacturers should monitor updates to the Medicare Coverage Database and contractor websites for updates to coverage and reimbursement for ESAs in the coming weeks. Manufacturer submission of public comments on the NCA may also be effective to ensure that CMS’s review of its ESA coverage and reimbursement policies and any ensuing NCD are based on sound medical evidence.