THOUSAND OAKS, Calif.--(BUSINESS WIRE)--Nov. 30, 2007--Amgen, Inc. (NASDAQ: AMGN) today announced that it had received interim results from the independent investigator-sponsored "PREPARE" study, an open-label, randomized, multicenter Phase 3 study of Aranesp(R) (darbepoetin alfa) in 733 neoadjuvant breast cancer patients receiving dose-dense, dose-intense preoperative chemotherapy compared to a standard preoperative chemotherapy regimen.
Initiated in 2002, the PREPARE study was developed, conducted and analyzed by the independent German Gynecological Oncology Study Group (AGO) and the German Breast Group. It was designed to evaluate the effects of preoperative chemotherapy using a sequential dose-dense and dose-intensified regimen of epirubicin, paclitaxel, and CMF compared to preoperative sequential administration of epirubicin and cyclophosphamide followed by paclitaxel in patients with breast cancer, with respect to event-free and overall survival, with or without Aranesp to prevent anemia and to potentially augment the therapeutic effects of the chemotherapy regimens. This study assessed both an experimental use of the drug to prevent anemia and an off-label regimen.
The pre-specified interim results relate to the study period when chemotherapy and Aranesp were administered, and specifically address the tumor response to chemotherapy at the time of surgery. In this analysis, there was no significant difference between the Aranesp and control groups.
The primary long-term follow up endpoints of the PREPARE study, including relapse-free survival time and overall survival, were designed to be analyzed when a pre-specified number of events had been observed. Available data as of Oct. 30, 2007, show numerically more deaths (37/377 for control and 50/356 for Aranesp) and tumor progression events (70/377 for control and 88/356 for Aranesp) on the Aranesp arm compared to the control group in the long-term follow up. A formal statistical analysis of survival is anticipated in early 2009.
"This interim analysis shows that the use of Aranesp to support neo-adjuvant chemotherapy has no significant impact on tumor response to chemotherapy at the time of surgery. No definitive conclusions should be drawn from the interim results of the long-term follow up until the final study report is completed," said the principal investigator Professor Michael Untch, M.D. of the AGO. "During the treatment period, there were as expected, no deaths, and we continue to monitor long-term follow-up results."
In the PREPARE study, patients were randomized to two different chemotherapy regimens and were then randomized to receive either no treatment or Aranesp (at a dose of 4.5 ug/kg every two weeks) to prevent anemia by maintaining hemoglobin concentrations between 12.5 g/dL and 13 g/dL, with dose withholding at levels greater than or equal to 13 g/dL. Patients in both groups entered the study with a mean hemoglobin level of 13.6 g/dL. In the study, Aranesp-treated patients maintained mean hemoglobin levels of 13.6 g/dL by the end of chemotherapy whereas subjects in the control group decreased to 12.6 g/dL.
These interim study results have been submitted to regulatory agencies, including the U.S. Food and Drug Administration (FDA). The final results will be submitted when available.
Aranesp Pharmacovigilance Program Update
The PREPARE study is one of five randomized, prospective clinical studies that are part of Amgen's current ongoing pharmacovigilance program, which was undertaken in agreement with the FDA following the Oncologic Drug Advisory Committee meeting in May 2004. Amgen has promptly submitted to regulatory agencies, including the FDA, all available data from the PREPARE study. Final data from two remaining pharmacovigilance studies including an additional breast cancer study are expected in 2009-2010.
Amgen recently announced the addition of six new proposed clinical trials to address the safety of ESAs in specific tumor types when used to treat anemia in cancer patients on chemotherapy. Upon agreement with the FDA, these studies will be added to the ongoing pharmacovigilance program. Based on the safety signals observed with higher hemoglobins, an additional study to evaluate the effect of hemoglobin targets on the risk/benefit profile of ESAs is also planned.
Aranesp was approved by the FDA in September 2001 for the treatment of anemia associated with chronic renal failure (CRF) for patients on dialysis and patients not on dialysis. In July 2002, the FDA approved weekly dosing of Aranesp for the treatment of anemia caused by concomitantly administered chemotherapy in patients with nonmyeloid malignancies and in March 2006, the FDA approved every-three-week dosing in these patients.
Important Aranesp Safety Information
WARNINGS: INCREASED MORTALITY, SERIOUS CARDIOVASCULAR and THROMBOEMBOLIC EVENTS, and TUMOR PROGRESSION
Renal failure: Patients experienced greater risks for death and serious cardiovascular events when administered erythropoiesis-stimulating agents (ESAs) to target higher versus lower hemoglobin levels (13.5 vs. 11.3 g/dL; 14 vs. 10 g/dL) in two clinical studies. Individualize dosing to achieve and maintain hemoglobin levels within the range of 10 to 12 g/dL.
-- ESAs shortened overall survival and/or time-to-tumor progression in clinical studies in patients with advanced breast, head and neck, lymphoid, and non-small cell lung malignancies when dosed to target a hemoglobin of greater than or equal to 12 g/dL.
-- The risks of shortened survival and tumor progression have not been excluded when ESAs are dosed to target a hemoglobin of less than 12 g/dL.
-- To minimize these risks, as well as the risk of serious cardio- and thrombovascular events, use the lowest dose needed to avoid red blood cell transfusions.
-- Use only for treatment of anemia due to concomitant myelosuppressive chemotherapy.
-- Discontinue following the completion of a chemotherapy course.
Aranesp is contraindicated in patients with uncontrolled hypertension.
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Forward Looking Statement
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