Amgen Warns of Mortality Risk for Off-Label Use of Aranesp

ROCKVILLE, Md., Jan. 29 -- For cancer patients with anemia not caused by chemotherapy, the off-label use of Aranesp (darbepoetin alfa) is ineffective and also boosts mortality, the FDA reported.

The agency drew attention to a letter to doctors from Amgen, pointing out that in a randomized placebo-controlled study of cancer patients with anemia not related to cancer therapy, Aranesp did not reduce the need for red blood cell transfusions and significantly increased mortality.

Aranesp is FDA-approved for treatment of anemia associated with chronic renal failure and for treatment of chemotherapy-related anemia in patients with nonmyeloid malignancies.

The mortality and transfusion findings come from an Amgen- sponsored phase III study that was designed to establish the effectiveness of Aranesp for a new indication.

However, the use of Aranesp for the off-label indication was associated with a 25% increase in mortality (hazard ratio 1.25, 95% confidence interval 1.04-151), according to Amgen.

Eighteen percent of patients in the Aranesp arm required RBC transfusions during the 16-week treatment phase versus 24% of patients in the placebo arm, (P=0.15), said Sean Harper, M.D., chief medical officer at Amgen.

The Amgen letter warned that Aranesp "should be used only in accordance with its approved product labeling for the treatment of anemia in patients with non-myeloid malignancies where anemia is due to the effect of concomitantly administered chemotherapy."

The trial enrolled 989 patients with hemoglobin at less than 11 g/dL, with active cancer, and who were not receiving myelosuppressive chemotherapy or radiotherapy.

Approximately 60% of patients enrolled had advanced stage IV disease.

The treatment period was supplemented with a pre-planned 16 week extension study to assess additional information on safety and effectiveness. Patients will be followed for a minimum of two years.

During the 16-week treatment phase 136 of the 515 patients randomized to Aranesp died versus 94 deaths among the 470 patients in the placebo arm.

With a median follow-up of 4.3 months deaths in the Aranesp arm increased to 250 (49%) versus 216 deaths in the placebo arm (46%).

The company said that details of the study will be presented and published in a peer-reviewed journal as soon as possible.