FDA announced on April 13, 2017 the elimination of the risk evaluation and mitigation strategy (REMS) for Aranesp (darbepoetin).
Aranesp was approved on September 17, 2001, for the treatment of anemia associated with chronic renal failure, including patients on dialysis and patients not on dialysis, and on March 23, 2006 for the treatment of anemia due to the effects of concomitant myelosuppressive chemotherapy. Aranesp is an Erythropoiesis-Stimulating Agent (ESA). ESAs work like the human protein erythropoietin, which stimulates bone marrow to make red blood cells.
Aranesp increases the risk of death, myocardial infarction, stroke, venous thromboembolism, and thrombosis of vascular access and tumor progression or recurrence. Aranesp can also lead to an increase in adverse cardiovascular events, hypertension, seizures, and severe anemia.
In 2008, FDA determined a REMS was necessary for the ESAs, Aranesp (darbopoetin alfa) and Epogen/Procrit (Epoetin alfa), to ensure the benefits for use as treatment for anemia associated with myelosuppressive chemotherapy outweigh its risks of shortened overall survival and/or increased risk of tumor progression or recurrence in patients with cancer. The REMS was approved in 2010. Under the ESA REMS program, referred to as the ESA APPRISE Oncology Program, healthcare providers that prescribed and/or dispensed Aranesp to patients with cancer and hospitals that dispensed Aranesp to patients with cancer were required to enroll and become certified in the ESA REMS. The ESA REMS also required a Patient and Healthcare Provider Acknowledgement Form be completed for each patient with cancer before the new ESA treatment course to ensure patients were counseled about the benefits and risks of these products.
The FDA determined that the ESA 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.
The agency made this determination based on an evaluation of the results of the REMS Assessments submitted by Amgen, Inc., 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.
- The drug utilization data that indicates appropriate prescribing of ESAs consistent with the FDA approved indication.
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, 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 the 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 l,="">10g>
- 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 that 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.
The FDA has released the REMS requirements for the ESA products, Epogen/Procrit and Aranesp, and the risks can be communicated by the current product prescribing information. The appropriate use of ESAs is supported by the CMS NCD, the American Society of Clinical Oncology (ASCO) and American Society of Hematology (ASH) clinical guidelines which are evidence-based guidelines intended to provide a basis for the standard of care in clinical oncology.
Prescribers should continue to follow the labeled directions for initiation and dose selection of Aranesp in order to treat anemia associated with chemotherapy in patients with cancer.
By eliminating the Aranesp REMS:
- Health care professionals who prescribe Aranesp for the treatment of anemia due to myelosuppressive chemotherapy will no longer be required to enroll and become certified in the ESA REMS patients with cancer to prescribe or dispense Aranesp.
- Prescribers will no longer be required to complete a Patient and Healthcare Provider Acknowledgement Form for each patient with cancer before the new Aranesp treatment course.
- Hospitals that dispense Aranesp to patients with cancer will no longer be required to enroll and become certified to dispense Aranesp.
While the REMS is no longer necessary to ensure the benefits outweigh the risks, the serious risks of shortened overall survival and/or increased risk of tumor progression or recurrence associated with Aranesp remains a concern. The prescribing information continues to note an increased risk of tumor progression or recurrence, as well as death, myocardial infarction, stroke, venous thromboembolism, and thrombosis of vascular access.