An FDA Advisory Committee has recommended the continued use of Aranesp (Darbepoetin alfa), a synthetic form of erythropoietin used to treat anemia in patients with mild to moderate chronic (long-term) kidney disease. Although the Advisory Committee’s recommendations are not binding, the FDA usually goes along with what their members say. The Committee voted 15 in favor with 1 abstention not to withdraw the medication. They had met after studies involving 4,000 participants showed that the risk of stroke for those taking Aranesp was equal to those on a placebo. The Advisers also voted on whether use should be limited to rescue therapy for individuals with extremely low levels of iron – they voted 9 to 5 that there should not be this limit.

Safety concerns have affected the sales of Aranesp since 2006. The medication is also used for treating patients with anemia caused by cancer chemotherapy. Treating kidney patients not on dialysis accounts for $600 million’s worth of Arenesp’s annual sales.

Reshma Kewalramani, M.D., FASN, executive director, Global Development at Amgen, the makers and marketers of Aranesp, said:

This Advisory Committee meeting is a valuable forum for the FDA, Amgen and the nephrology community to review the results from TREAT, which further inform use of ESAs in patients with chronic renal failure who are not on dialysis. We look forward to sharing our analyses of TREAT and describing proposed label changes that will help guide nephrologists in focusing their use of ESA therapy on patients most likely to benefit.

TREAT is the largest study of erythropoiesis-stimulating agent (ESA) use in patients with chronic renal failure. It is a double-blind, randomized, placebo-controlled Phase III study of individuals with moderate kidney dysfunction (not on dialysis), with moderate anemia as well as diabetes Type 2, and were treated to a hemoglobin target of 13 g/dL, a higher level than recommended in the current approved ESA label, Amgen informs.

The trial’s endpoints of all-cause mortality reduction or cardiovascular morbidity reduction were not met, the study also showed a higher risk of stroke in the Aranesp group of patients.

Amgen stresses that the cardiovascular risks have been included in the boxed warning of the FDA-approved ESA labels since 2007. Amgen adds that since December 2009, the warnings have been strengthened to include the specific stroke risk.

Amgen proposes that ESA labels be altered, limiting treatment to those most likely to benefit – patients with significant anemia who have a high risk for transfusion and for whom avoiding transfusion is clinically important, including individuals for whom preserving kidney transplant eligibility is important. For patients with chronic renal failure who are receiving dialysis (not studied in TREAT) the benefits are clear and unchanged, the company adds.

Robert Toto, M.D., University of Texas Southwestern Medical Center, said:

The nephrology community has, and will continue to gain, significant understanding about the treatment of anemia in patients with chronic kidney disease not on dialysis from this large and rigorously designed and conducted clinical trial. First and foremost, TREAT has informed us that the risks of treatment may outweigh the benefits for some patients with chronic kidney disease and anemia who are not on dialysis. However, ESAs remain an important therapeutic option for patients on dialysis, where the benefits are clear, and for certain patients not on dialysis; specifically those with significant anemia in whom blood transfusion avoidance is important, especially to preserve eligibility for kidney transplantation, the preferred treatment option for patients with failing kidneys.

Over 26 million Americans are affected by chronic kidney disease, which invariably leads to progressive kidney damage and impaired kidney function. Chronic kidney disease is most commonly caused by diabetes Type 2 or hypertension (high blood pressure). When a person with chronic kidney disease develops kidney failure there are two options for staying alive – regular long-term dialysis or a kidney transplant. A common complication of chronic kidney disease is anemia, which may occur during the disease’s early stages. As kidney function gets worse anemia becomes more common.

Aranesp was approved in both the USA and the European Union in 2001 for the treatment of anemia linked to chronic renal failure for patients not on dialysis as well as those on dialysis. In 2008 the European Commission updated Aranesp use also for chronic renal failure patients with symptomatic anemia.

The FDA approved Aranesp in 2002 for anemia treatment caused by chemotherapy in individuals with nonmyeloid malignancies. In 2002 the European Commission approved Aranesp treatment for anemia caused by concomitantly administered chemotherapy in patients with non-haematological malignancies. In 2003 its use was extended in Europe to include non-myeloid malignancies in patients receiving chemotherapy.

Sources: FDA, Amgen

Written by Christian Nordqvist