Aranesp DAHANCA 10 Study Results Presented at ECCO Annual Meeting
This independent, investigator-sponsored study is a component of Amgen's ongoing Aranesp pharmacovigilance program and was designed to evaluate the experimental circumstance of whether using Aranesp to maintain hemoglobin (Hb) levels between 14.0 to 15.5 g/dL results in better outcomes for patients with squamous cell carcinoma of the head and neck (HNSCC) by allowing more oxygen to reach the tumor, making it more sensitive to radiotherapy. Aranesp is not indicated for concomitant treatment with radiotherapy alone and the Hb targets in this study exceeded the current approved labeling in both Europe and the U.S.
The study investigators completed their analysis of the data in July 2007 and have concluded that patients with primary HNSCC who were treated with Aranesp had significantly poorer tumor control after radiotherapy. Of 515 patients eligible for analysis, the results demonstrated a poorer outcome with Aranesp treatment in 5-year loco-regional control (56 percent with Aranesp versus 69 percent for the control group; RR: 1.44 (1.06-1.96), p=0.02), the primary endpoint for the study.
There were no significant differences in overall survival (RR: 1.28 (0.98-1.68), p=0.08), the risk of developing distant metastases or in non-cancer related deaths. There was also no enhanced risk of cardiovascular events observed in the Aranesp arm. Systematic imaging was not applied in this study. Instead, the study relied on clinical methodology for detection of disease persistence or recurrence. This method is not the U.S. or European regulatory standard for assessing disease progression in HNSCC.
The study was conducted by the independent DAHANCA study group, and thus Amgen did not have control over the study conduct or data analysis. Amgen has not had the opportunity to validate the assessment of the raw data. In early December 2006, Amgen shared with regulatory agencies, including the European Agency for the Evaluation of Medicinal Products (EMEA) and the U.S. Food and Drug Administration (FDA), the preliminary interim data report that was posted on the DAHANCA study group's Web site.
The boxed warning section of the U.S. labeling for erythropoiesis-stimulating agents (ESAs) was updated in March 2007 to include information about the DAHANCA 10 preliminary results.
"Aranesp is approved to treat anemic patients receiving chemotherapy, and is not approved for use by the FDA or EMEA for the experimental indication investigated in this trial," said Willard Dere, M.D., Amgen senior vice president and international chief medical officer. "Amgen continues to recommend the use of Aranesp to treat patients with anemia only in accordance with its approved product labeling, and remains committed to providing patients and their physicians with the most accurate information to make informed treatment decisions."
Aranesp is a recombinant erythropoietic protein (a protein that stimulates production of red blood cells, which carry oxygen). Amgen revolutionized the treatment of anemia with the development of recombinant erythropoietin, Epoetin alfa. Building on this heritage, Amgen developed Aranesp, a unique erythropoiesis stimulating protein, which contains two additional sialic acid-containing carbohydrate chains compared to the epoetin alfa molecule and remains in the bloodstream longer than epoetin alfa as demonstrated by its longer half-life.
Aranesp was granted marketing authorization by the European Commission in 2001 for the treatment of anemia associated with chronic renal failure (CRF), also known as chronic kidney disease (CKD), in adults and pediatric subjects 11 years of age or older. In 2002, the European Commission approved Aranesp for the treatment of anemia in adult cancer patients receiving chemotherapy with solid tumors. This patient population was subsequently expanded in 2003 to include treatment of symptomatic anemia in adult cancer patients with non-myeloid malignancies receiving chemotherapy. Approval was granted in 2004 for extended dosing intervals of once-every-three-weeks in the treatment of anemia in adult cancer patients with non-myeloid malignancies who are receiving chemotherapy and up to once-per-month Aranesp administration in the treatment of anemia in CKD patients not on dialysis. In 2006, the Aranesp label was updated to allow CKD patients on dialysis to switch from rHuEPO one to three times a week to Aranesp every two weeks. In 2007, the Aranesp label was updated to allow for treatment of anemia associated with CRF, in all European pediatric patients on dialysis or not on dialysis.
Aranesp was approved by the U.S. Food and Drug Administration (FDA) in September 2001 for the treatment of anemia associated with 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 EU Aranesp Safety Information
Aranesp is contraindicated in patients with uncontrolled hypertension. Erythropoietic therapies may increase the risk of thrombotic and other serious events; regional guidelines should be referred to for target and maximum hemoglobin levels, and dose adjustment rules should be performed in line with regional prescribing information.
The most commonly reported side effects in clinical trials were arthralgia, edema, injection site pain, and thromboembolic event reactions. Prescribers are recommended to consult regional prescribing information before prescribing Aranesp, including side-effects, precautions and contra-indications.
Important U.S. Aranesp Safety Information
Use the lowest dose of Aranesp(R) that will gradually increase the hemoglobin concentration to the lowest level sufficient to avoid the need for red blood cell transfusion.
Aranesp(R) 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
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 or radiation therapy. ESAs are not indicated for this population.
Patients receiving ESAs pre-operatively for reduction of allogeneic red blood cell transfusions: A higher incidence of deep venous thrombosis was documented in patients receiving Epoetin alfa who were not receiving prophylactic anticoagulation. Aranesp(R) is not approved for this indication.
Aranesp is contraindicated in patients with uncontrolled hypertension.
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Sabeena Ahmad, +41 41 3692 530 (EU media, oncology)
Ashleigh Koss, 805-313-6151 (US media, oncology)
Arvind Sood, 805-447-1060 (investors)
Posted: September 2007