New erythropoiesis-stimulating agents: how innovative are they?

Recombinant human erythropoietin (rHuEPO) has revolutionized the management of anemia in patients with chronic kidney disease. However, being similar to the naturally occurring molecule, rHuEPO is not a perfect pharmaceutical. Given its relatively short halflife, it requires a relatively frequent administration schedule. Moreover, it can be administered only subcutaneously or intravenously and it is unstable at room temperature, making necessary a strict cold chain. Pharmacological research has focused on the development of new agents in order to circumvent these relative disadvantages. New-generation erythropoietin-stimulating agents containing increased carbohydrate content (i.e. darbepoetin-alpha) or a large water-soluble polyethylene glycol moiety (continuous erythropoiesis receptor activator) are already available or nearly for clinical use and allow less frequent administration schedules than rHuEPO. Hematide, which is a dimeric peptide with chemical structure unrelated to EPO, is undergoing phase III clinical trials. Other possible strategies currently under research include fusion EPO proteins, gene therapy, hypoxia-inducible transcription factor stabilizers, GATA inhibition and hematopoietic cell phosphatase inhibition.