FDA Determines Erythropoiesis-Stimulating Agents Risk Evaluation and Mitigation Strategy No Longer N

In 2017, the FDA determined that the ESA Risk Evaluation and Mitigation Strategy (REMS), which was limited to the use of Epogen/Procrit and Aranesp to treat patients with anemia due to associated myelosuppressive chemotherapy is no longer necessary to ensure that the benefits of Epogen/Procrit and Aranesp outweigh its risks of shortened overall survival and/or increased risk of tumor progression or recurrence in patients with cancer.

Epoetin alfa and darbepoetin alfa are Erythropoiesis-Stimulating Agents (ESAs), approved for the treatment of anemia (low red blood cells) resulting from chronic kidney disease, chemotherapy, certain treatments for Human Immunodeficiency Virus (HIV), and also to reduce the number of blood transfusions during and after certain major surgeries. ESAs work like the human protein erythropoietin, which stimulates bone marrow to make red blood cells. Epoetin alfa and darbepoetin alfa are manufactured by Amgen, Inc.

The FDA made this determination based on an evaluation of the results of the REMS Assessments submitted by Amgen and additional FDA analyses to understand the impact of the various regulatory and other actions on the use of ESAs.

The REMS Assessment showed that the results from surveyed prescribers demonstrate acceptable knowledge of the product risks of decreased survival and/or the increased risk of tumor progression or recurrence and the need to counsel patients about these risks. It also showed that the drug utilization data indicates appropriate prescribing of ESAs consistent with the intended use as a treatment alternative to RBC transfusion for anemia associated with myelosuppressive chemotherapy.

The FDA conducted an evaluation of the impact of multiple actions, including the ESA REMS, on the utilization of the ESAs using sponsor-submitted data from outpatient oncology practices between 2006 and 2014. During 2004-2009, the FDA took multiple regulatory actions, including labeling changes. In 2007, the Center for Medicare and Medicaid Services (CMS) made a National Coverage Determination (NCD) to limit coverage of ESAs for non-renal disease indications. These actions coincided with a decrease in the proportion of patients receiving chemotherapy using ESAs, an increase in the proportion of patients receiving chemotherapy who initiate ESAs at a hemoglobin level <10g/dl, and an increase in the proportion of patients who initiate ESAs at a dosage consistent with product prescribing. information.

Full implementation of the ESA REMS in 2011 had minimal impact on trends in these three ESA utilization metrics beyond the changes observed after the CMS coverage determination and multiple other FDA regulatory actions.

This information led the FDA to conclude it is no longer necessary to require the certification of prescribers and hospitals that prescribe and/or dispense ESAs to patients with cancer in order to ensure the benefits outweigh the risks.