FDA Announcement Regarding Aranesp® Evolving Safety Information

The following is a message from the FDA's Office of Oncology Drug Products Director, Dr. Richard Pazdur:

FDA was recently notified of the results of a 989 patient, multicenter, double-blind, randomized, placebo-controlled study of Aranesp® (darbepoetin alfa, Amgen, Thousand Oaks, CA) in anemic cancer patients not receiving concurrent cytotoxic therapy. The study results demonstrated an increased mortality in patients receiving Aranesp® compared to those receiving placebo (hazard ratio 1.25; 95 percent confidence interval: 1.04, 1.51). In addition, Aranesp® did not reduce red blood cell transfusion requirements in these patients. The target hemoglobin in the Aranesp® treatment group was 12 g/dl. The findings in this study may be applicable to other erythropoiesis-stimulating agents (ESA). Additional information on this study is in Amgen's letter posted on FDA's MedWatch Web site at http://www.fda.gov/medwatch/safety/2007/safety07.htm#Aranesp.

FDA also directs prescribers' attention to the interim results of the Danish Head and Neck Cancer Study Group trial (DAHANCA 10) comparing radiation therapy alone to radiation therapy plus Aranesp® in the treatment of advanced head and neck cancer. The data monitoring committee (DMC) recommended the trial's termination. This open-label, randomized trial was designed to test the hypothesis that use of Aranesp® to maintain a hemoglobin of 14.0-15.5 g/dL during radiotherapy would result in superior loco-regional disease control. The DMC reported an approximate 10 percent difference in 3-year loco-regional control (p=0.01) in favor of the control group. A statistically non-significant difference in overall survival (p=0.08) also favoring the control arm was observed. These results are consistent with findings by Henke et al that are described in the approved product labeling (under Precautions, Tumor Growth Factor Potential) and were presented at a May 4, 2004, Oncologic Drugs Advisory Committee (ODAC) meeting (transcript available at http://www.fda.gov/ohrms/dockets/ac/cder04.html#Oncologic). Additional information on the DAHANCA 10 study is available at http://conman.au.dk/dahanca/.

FDA has previously noted that increased mortality, possible tumor promotion, and thromboembolic events have been observed in patients receiving ESAs when dosing has targeted hemoglobin levels >12 gm/dL. The recommended labeled target hemoglobin in current product labeling is 12 gm/dl. Please refer to the above 2004 ODAC transcript for further discussion.

FDA is planning to review and discuss the safety and efficacy of ESAs at an upcoming meeting of the ODAC.

Aranesp® was approved in July, 2002, for the treatment of anemia in patients with non-myeloid malignancies where anemia is attributed to the effects of concomitantly administered chemotherapy. Full prescribing information for Aranesp®, including clinical trial information, safety, dosing, drug-drug interactions, and contraindications is available at: http://www.fda.gov/cder/foi/label/2006/103951s5097lbl.pdf. A revised FDA Healthcare Professional Sheet regarding evolving safety issues with ESAs is posted at http://www.fda.gov/cder/drug/infopage/RHE/default.htm.

Healthcare professionals should report all serious adverse events suspected to be associated with the use of any medicine and device to FDA's MedWatch Reporting System by completing a form online at http://www.fda.gov/medwatch/report.htm, by faxing (1-800-FDA-0178) or mailing the postage-paid address form provided online, or by telephone (1-800-FDA-1088).