FDA MedWatch: Aranesp (darbepoetin alfa) Study Showing the Drug Ineffective in Reducing RBC Transfusions or Fatigue in Cancer Patients with Anemia and a Higher Mortality Rate Observed in the Aranesp Treatment GroupMedWatch - The FDA Safety Information and Adverse Event Reporting Program
ROCKVILLE, MD., Jan. 27, 2007--Amgen notified the oncology medical community of the results of a large, multicenter, randomized, placebo-controlled study showing that Aranesp was ineffective in reducing red blood cell transfusions or fatigue in patients with cancer who have anemia that is not due to concurrent chemotherapy. The study also showed higher mortality in patients receiving Aranesp. Aranesp is approved for the treatment of patients with anemia caused by the chemotherapy treatment of the malignant disease and should only be used in accordance with its approved product labeling.
Read the Dear Healthcare Professional letter below:
January 26, 2007
Dear Health Care Professional:
Amgen wishes to inform you of the results of a large, multicenter, randomized, placebo-controlled study showing that Aranesp was ineffective in reducing RBC transfusions in patients with cancer who have anemia that is not due to concurrent chemotherapy. In addition, this study showed higher mortality in patients receiving Aranesp. In the study, Aranesp® (darbepoetin alfa) was compared to placebo in patients with active malignant disease not receiving or expected to receive chemotherapy or radiation therapy. This study was designed to establish the effectiveness of Aranesp in this new indication and failed to meet its primary endpoint of reducing RBC transfusions in the Aranesp treatment group. This study was not optimal in design to establish the effect on survival, a safety endpoint, however more deaths occurred in the Aranesp treatment group when compared to the placebo group.
Aranesp is not approved for use in this population. Aranesp is approved for the treatment of patients with anemia, which is caused by chemotherapy treatment of their malignant disease, rather than the underlying malignant disease itself. 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.
Study Description. This Amgen-sponsored study was a Phase 3, double-blind, randomized, placebo controlled clinical study, monitored by an independent Data Safety Monitoring Board. The treatment period was 16 weeks; additional information on safety and effectiveness will be obtained from a 16 week extension study in which randomized treatment with Aranesp or placebo was continued. All patients have completed this extension study. Survival follow up will continue on patients for a minimum of 2 years. The target hemoglobin in the Aranesp treatment group was 12 g/dl. A total of 989 patients with hemoglobin (Hgb) < 11 g/dl, with active cancer, and who were not receiving myelosuppressive chemotherapy or radiotherapy were enrolled. Approximately 60% of patients enrolled had advanced (stage IV) disease.
The final analysis of the initial 16-week treatment period did not show a statistically significant effect on the primary efficacy endpoint (Hazard ratio 0.89; 95% Confidence Interval: 0.65, 1.22), with an incidence of RBC transfusions of 24% in the placebo vs. 18% in the Aranesp group, p=0.15.
In the 16-week treatment phase of the study, more deaths were reported in the Aranesp treatment group (26% (136/515)) than the placebo group (20% (94/470)). With median survival follow-up of 4.3 months the absolute number of deaths was greater in the Aranesp treatment group (216/470=46% and 250/515=49% for the placebo and the Aranesp arms, respectively, Hazard Ratio 1.25; 95% Confidence Interval: 1.04, 1.51). Follow-up of surviving patients continues. Details of this study will be presented and published in a peer-reviewed setting as soon as possible.
A copy of the prescribing information for Aranesp is enclosed. Should you have any questions or require further information regarding the use of Aranesp, please contact Amgen’s Medical Information Connection™ at 1-800-77AMGEN or online at http://www.amgenmedinfo.com
Sean Harper, M.D.
Senior Vice President
Global Development and
Corporate Chief Medical Officer
Call 1-888-INFO-FDA (1-888-463-6332)
Posted: January 2007
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