Erythropoietin mimetic peptides and erythropoietin fusion proteins for treating anemia of chronic kidney disease

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Purpose of reviewFirst generation erythropoiesis stimulating agents (ESAs) have short duration of action which requires administration once weekly or greater. Second generation ESAs were developed which have longer duration of action and can be administered one to two times monthly. Erythropoietin (EPO) mimetic peptides (EMPs) activate the EPO receptor but have no structural analogy to EPO, offering the potential for lower cost as they are not biologic drugs. The first approved EMP, peginesatide, was withdrawn from the market within a year of its approval because of fatal anaphylactic reactions. In this review, we summarize recent progress regarding the development of newer, possibly less toxic, EMPs. We also summarize the development of EPO fusion proteins which fuse EPO with a portion of an immunoglobulin molecule or another EPO molecule, achieving a longer duration of action and less frequent dosing.Recent findingsAGEM400(hydroxyethyl starch) and pegolsihematide are EMPs in phase II clinical trials. Three EPO fusion proteins are under development, two in phase I and one in phase II.SummaryThe future success of EMPs is limited by the prior experience with peginesatide and EPO fusion proteins do not offer cost savings or longer duration of action than currently available ESAs.

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