THOUSAND OAKS, Calif.--(BUSINESS WIRE)--April 16, 2007--Amgen (Nasdaq:AMGN) today presented the results from a randomized, double-blind, placebo-controlled Phase 3 study evaluating the efficacy and safety of Aranesp(R) (darbepoetin alfa) for the treatment of anemia in patients with active cancer not receiving chemotherapy or radiotherapy ("the 103 study"). Aranesp is not approved for use by the FDA or EMEA in these patients. These results were presented in an oral session at the 2007 American Association for Cancer Research (AACR) annual meeting in Los Angeles, Calif. (AACR Abstract #LB-3).
As reported in January, the study did not meet its primary endpoint of reducing red blood cell (RBC) transfusions in the Aranesp treatment group. Transfusion occurrences from weeks 5 to 17 favored Aranesp but were not statistically significant between the groups (hazard ratio: 0.85, p=0.32). Among those receiving Aranesp, there was a significantly higher proportion of patients with a hemoglobin response (p less than 0.0001), hemoglobin correction (p less than 0.001), and hematopoietic response (p=0.002) compared with placebo.
The adverse event rate was similar between the groups. However, the overall number of deaths was greater in the Aranesp group (48.5 percent versus 46 percent in placebo; hazard ratio: 1.29; p=0.006). In post-hoc analyses adjusting for stratification factors at randomization and sex, stage IV disease, prior chemotherapy use and prior radiotherapy use, there remained a significant difference in survival between the groups. However, hazard ratios and statistical significance diminished when the analyses were further adjusted for known prognostic factors including baseline ECOG status, tumor type, tumor stage, baseline FACT-F cutoff at median and baseline Hb (hazard ratio: 1.17, p=0.11).
"This study evaluated ESA treatment for patients with active cancer, not receiving chemotherapy or radiation, who are anemic due to the cancer itself. Unfortunately, the benefit of ESA treatment was not observed in these gravely ill patients," said John Glaspy, M.D., professor, David Geffen School of Medicine, University of California at Los Angeles. "Since this was not designed as a survival study and statistical significance diminished when the analyses were adjusted for known prognostic factors, there is no clear explanation for the increase of deaths in the Aranesp group."
About the Study
This Phase 3 study was designed to evaluate the efficacy and safety of Aranesp 6.75 mcg/kg administered every four weeks for the treatment of anemia in cancer patients not receiving chemotherapy or radiotherapy. The study was conducted in 21 countries, including sites in Western Europe, Central and Eastern Europe, Australia and North America. The majority of patients (60 percent) were from Central and Eastern Europe.
Patient eligibility included: greater than or equal to 18 years, nonmyeloid malignancy (with active disease), hemoglobin (Hb) less than or equal to 11 g/dL, and no chemotherapy or radiotherapy treatment within four weeks of screening or during the study. Patients (n=985) were randomized to Aranesp 6.75 mcg/kg or placebo every four weeks, with an end of study visit at week 19, and two years of follow up to evaluate survival. Patients were stratified by screening Hb (less than 10 g/dL or greater than or equal to 10 g/dL), geographic region (Europe versus rest of world), RBC transfusion in the prior 12 weeks, tumor type/treatment (specifically, diagnoses of chronic lymphocyctic leukemia or low grade lymphoma, ongoing hormonal or antibody therapy versus all other eligible patients), and ECOG status (0-1, 2).
Demographics were broadly similar between the groups. The mean (SD) age was 64.1 (11.6) years; the most common cancers were non-small cell lung (18 percent), breast (13 percent), and prostate (11 percent); most patients had disease stage III or IV (82 percent) and an ECOG status of 0 or 1 (72 percent); and baseline Hb was 9.5 g/dL in each group.
However, there were more men in the Aranesp group (56 percent) compared to the placebo group (47 percent) and overall survival was worse for men than women (hazard ratio: 1.38 versus 0.99, respectively). More patients received prior chemotherapy in the Aranesp group (73 percent versus 66 percent in placebo). The mean (SD) number of days between prior chemotherapy and first study drug dose was 262 (572) days for the Aranesp group compared to 315 (660) for the placebo arm.
Aranesp was approved by the U.S. Food and Drug Administration (FDA) in September 2001 for the treatment of anemia associated with chronic renal failure (CRF), also known as chronic kidney disease (CKD), for patients on dialysis and patients not on dialysis. In July 2002, the FDA approved weekly dosing of Aranesp for the treatment of chemotherapy-induced anemia in patients with nonmyeloid malignancies and in March 2006, the FDA approved every-three-week dosing in these patients.
Important Safety Information
Use the lowest dose of Aranesp that will gradually increase the hemoglobin concentration to the lowest level sufficient to avoid the need for red blood cell transfusion (see DOSAGE and ADMINISTRATION in the prescribing information).
Aranesp and other erythropoiesis-stimulating agents (ESAs) increased the risk for death and for serious cardiovascular events when administered to target a hemoglobin of greater than 12 g/dL (see WARNINGS: Increased Mortality, Serious Cardiovascular and Thromboembolic Events).
Cancer Patients: Use of ESAs
-- shortened the time to tumor progression in patients with advanced head and neck cancer receiving radiation therapy when administered to target a hemoglobin of greater than 12 g/dL;
-- shortened overall survival and increased deaths attributed to disease progression at 4 months in patients with metastatic breast cancer receiving chemotherapy when administered to target a hemoglobin of greater than 12 g/dL;
-- increased the risk of death when administered to target a hemoglobin of 12 g/dL in patients with active malignant disease receiving neither chemotherapy nor radiation therapy. ESAs are not indicated for this population.
(See WARNINGS: Increased Mortality and/or Tumor Progression in the prescribing information).
The Aranesp prescribing information, including important safety information and boxed warning, may be accessed at www.aranesp.com.
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Aranesp prescribing information can be accessed by calling 800-772-6436 or by logging on to www.aranesp.com.
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