Erythropoiesis stimulating agents approaches to modulate activity

Abstract

Recombinant human erythropoietin (rHuEPO), such as the approved agents epoetin alfa and epoetin beta, has been used successfully for over 20 years to treat anemia in millions of patients. However, due to the relatively short half-life of the molecule (approximately 8 hours), frequent dosing may be required to achieve required hemoglobin levels. Therefore, a need was identified in some anemic patient populations for erythropoiesis stimulating agents with longer half-lives that required less frequent dosing. This need led to the development of second generation molecules which are modified versions of rHuEPO with improved pharma-cokinetic and pharmacodynamic properties such as darbepoetin alfa, a hyperglycosylated analog of rHuEPO, and pegzyrepoetin, a pegylated rHuEPO. Third generation molecules, such as peginesatide, which are peptide mimetics that have no sequence homology to rHuEPO have also recently been developed. The various molecular, pharmacokinetic, and pharmacodynamic properties of these and other erythropoiesis stimulating agents will be discussed in this review.

The Effect of Erythropoiesis-Stimulating Agents in Patients with Therapy-Refractory Autoimmune Hemolytic Anemia

“…Recombinant ESAs are used for the treatment of anemia in patients with various underlying diseases [13], but has not yet been extensively investigated in patients with AIHA. The reason behind why this agent has not been used in the treatment of AIHA might be due to the fact that erythropoiesis in these patients is usually increased, leading to the assumption that in such cases ESAs are not indicated.…”

Injectables and Depots to Prolong Drug Action of Proteins and Peptides

“…Darbepoetin-α has proven itself to be clinically beneficial. Compared to the unmodified protein, darbepoetin-α exhibits a 3-fold extended half-life, permitting dosing once weekly or once every two weeks [ 65 ]. A synthetic erythropoiesis protein (SEP) has been described by Kochendoefer et al [ 66 ] as an alternative to other glycosylated EPO motifs produced recombinantly [ 66 ].…”

Hepcidin: Homeostasis and Diseases Related to Iron Metabolism

“…The erythroid precursors BFU-E (burst-forming unit-erythroid) and CFU-E (colony-forming unit-erythroid) induce the expression of erythropoietin receptors as well as transferrin receptors. Erythropoietin acts on erythroid progenitors to induce differentiation and erythroid maturation pathways such as the STAT5, phosphoinositol-3-kinase, MAP kinase, and protein kinase C pathways, which remain active throughout the process of maturation and differentiation [42,43,44]. …”