Amgen said the European Commission reached its final decision to amend the prescribing information for Aranesp (darbepoetin alfa) based on the positive opinion from the European Committee for Medicinal Products for Human Use (CHMP) in January 2008. The CHMP granted positive opinions for all centrally-authorized Erythropoiesis Stimulating Agents (ESAs) in the European Union (EU), each of which will receive European Commission Decisions.
A summary of key changes to the prescribing information for Aranesp are: Amending the SmPCs to stipulate a uniform target haemoglobin range of 10 g/dL to 12 g/dL with guidance to avoid sustained haemoglobin levels above 12 g/dL; Providing guidance for dosage adjustments to maintain haemoglobin concentration between 10-12 g/dL once the therapeutic objective for an individual patient has been achieved. Patients should be monitored to ensure the lowest approved dose is used to maintain haemoglobin at a level that controls the symptoms of anaemia; Amending the Posology and method of administration section to recommend that Aranesp should be administered to cancer patients with symptomatic chemotherapy induced anaemia (CIA) (e.g. haemoglobin concentration equal to or less than 10 g/dL (6.2 mmol/l)); Amending the therapeutic indication for chronic renal failure (CRF) from "treatment of anaemia associated with CRF" to "treatment of symptomatic anaemia associated with CRF" in adult and paediatric patients; Amending the Special Warnings to indicate ESAs have not been shown to improve overall survival or decrease the risk of tumour progression in patients with anaemia associated with cancer. ESA trials have shown an unexplained excess mortality in association with high target haemoglobin concentrations (greater than 12 g/dL), including (1) shortened time to tumour progression in patients with advanced head and neck cancer receiving radiation therapy; (2) shortened overall survival in patients with metastatic breast cancer receiving chemotherapy; (3) increased risk of death when administered to target a haemoglobin of 12g/dL (7.5 mmol/l) in patients with active malignant disease receiving neither chemotherapy nor radiation therapy. Clinical trials in patients with CKD have also observed an increased risk of death and serious cardiovascular events when ESAs were administered to target a haemoglobin of greater than 12g/dL (7.5 mmol/l).
Aranesp was granted marketing authorisation by the European Commission in 2001 for the treatment of anaemia associated with CRF, in adults and paediatric subjects 11 years of age or older. In 2002, the European Commission approved Aranesp for the treatment of anaemia in adult cancer patients receiving chemotherapy with solid tumours. This patient population was subsequently expanded in 2003 to include treatment of symptomatic anaemia 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 anaemia in adult cancer patients with non-myeloid malignancies who are receiving chemotherapy and up to once-per-month Aranesp administration in the treatment of anaemia in CKD patients not on dialysis. In 2006, the Aranesp label was updated to allow CKD patients on dialysis to switch from recombinant human erythropoietin (rHuEPO) one to three times a week to Aranesp every two weeks. In 2007, the Aranesp label was updated to allow for treatment of anaemia associated with CRF, in all European paediatric patients on dialysis or not on dialysis.
Aranesp was approved by the US Food and Drug Administration (FDA) in September 2001 for the treatment of anaemia 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 anaemia caused by concomitantly administered chemotherapy in patients with nonmyeloid malignancies and in March 2006, the FDA approved every-three-week dosing in these patients.