New Treatment Approaches in Chronic Kidney Disease-associated Anaemia

Abstract

Recombinant human erythropoietin (rHuEPO) is an effective agent for the treatment of anaemia in patients with chronic kidney disease. However, given its relatively short half-life, it requires a relatively frequent administration schedule. Moreover, it can be administered only subcutaneously or intravenously and is unstable at room temperature, making a strict cold chain control necessary. Pharmacological research has focused on the development of new agents to circumvent these relative disadvantages. Some long-acting erythropoietin-stimulating agents (ESAs) are already available for clinical use that require a less-frequent administration schedule. Peginesatide (Hematide™), which is a small dimeric peptide with a chemical structure unrelated to EPO, has recently ended phase III clinical trials. Other new molecules undergoing clinical development are CNTO 530 and CNTO 528, ACE-011 and hypoxia-inducible transcription factor stabilisers. The latter have the advantage that they can be administered orally but their clinical development faces a significant hurdle following a case of fatal hepatitis. Newer molecules in this class are undergoing clinical evaluation. Other strategies, such as EPO fusion proteins, agonistic antibodies targeting the EPO receptor and gene therapy have only been tested in animal models or are undergoing pre-clinical evaluations. Before clinical approval, all these new strategies need to address safety concerns raised recently about the use of ESAs regarding possible increased cardiovascular risks following targeting to high haemoglobin levels and/or exposure to excessive doses without reaching a target in both higher and lower haemoglobin groups, and reduced survival and tumour control in the oncology setting. Many of these molecules will also need careful evaluation for possible immunogenicity.