FDA approved methoxy polyethylene glycol-epoetin beta on November 14, 2007, for the treatment of anemia associated with chronic renal failure in adults, including those undergoing dialysis and those not undergoing dialysis.
Endogenous erythropoietin production is impaired in patients with chronic renal failure; erythropoietin deficiency is the primary cause of anemia in these patients. Methoxy polyethylene glycol-epoetin beta is an erythropoiesis-stimulating agent (ESA) that has a longer half-life and greater in vivo activity than erythropoietin. This agent was approved on November 14, 2007, for the treatment of anemia associated with chronic renal failure in adults, including those undergoing dialysis and those not undergoing dialysis.
Efficacy. The efficacy of this agent was evaluated in 6 open-label, multicenter trials that randomized patients to receive methoxy polyethylene glycol-epoetin beta or a comparator ESA. In the first study, patients not undergoing dialysis were randomized to receive methoxy polyethylene glycol-epoetin beta (starting dose, 0.6 mcg/kg administered via subcutaneous [SC] injections once every 2 wk) or darbepoetin alfa (starting dose, 0.45 mcg/kg administered via SC injections once every wk) for 28 weeks. In the second study, patients undergoing dialysis were randomized to receive methoxy polyethylene glycol-epoetin beta (starting dose, 0.4 mcg/kg administered via intravenous [IV] injections once every 2 wk) or epoetin alfa or beta (starting dose consistent with manufacturer's recommendations and administered via IV injections 3 times/wk) for 24 weeks. In the first study, 98% of methoxy polyethylene glycol-epoetin beta-treated patients achieved a hemoglobin (Hb) increase of ≥1 g/dL to a level of ≥11 g/dL versus 96% of patients treated with darbepoetin alfa. In the second study, 93% of methoxy polyethylene glycol-epoetin beta-treated patients achieved this end point versus 91% of patients treated with epoetin alfa or beta. In the other 4 studies, patients who were currently being treated with ESAs were randomized to receive methoxy polyethylene glycol-epoetin beta via SC or IV injections once every 2 or 4 weeks (starting dose determined based on previous ESA dose) or to continue with their current ESA dosing schedule. In all studies, treatment with methoxy polyethylene glycol-epoetin beta maintained Hb concentrations within the targeted range.
Safety. Patients treated with ESAs to target Hb levels of 13.5 or 14 g/dL experienced a greater risk of death and serious cardiovascular events than those treated to a target of 10 or 11.3 g/dL in clinical trials. ESAs have also been demonstrated to shorten the time to tumor progression or survival when used to target an Hb level ≥12 g/dL in patients with advanced head and neck cancer, metastatic breast cancer, lymphoid malignancy, and non-small cell lung cancer. ESA-treated patients may experience pure red cell aplasia and severe anemia associated with the development of neutralizing antibodies to erythropoietin. The most common adverse events associated with methoxy polyethylene glycol-epoetin beta include hypertension, diarrhea, nasopharyngitis, upper respiratory tract infection, and headache.