A Phase 3 Study of Efepoetin Alfa for Treatment of Anemia in Patients With Chronic Kidney Disease on Dialysis

Efepoetin alfa (Epoetin-Fc fusion protein, GX-E2 or GX-E4,) is a novel long-acting erythropoietin-hybrid fragment crystallizable (Fc) fusion protein developed by Genexine, intended for treatment and maintenance of anemia due to CKD with or without dialysis. Its drug substance is a recombinant form of human EPO and hybrid Fc (hyFc®) fragment consisting of 2 subunits with a total of 411 amino acid residues. Each subunit contains an EPO molecule linked to a hybrid Fc fragment of c terminal of CH2 and CH3 regions from IgG4 and to N-terminal of CH2 region and the hinge sequence from IgD. These 2 subunits are joined by a single disulfide bond at the hinge region of each subunit. Half-life is 138.5-157.9 hours. It is an acidic glycoprotein of about 30 kDa and comprises 165 amino acids and 4 glycans. Circulating EPO exhibits several glycosylation isoforms that differ in electrical charge and biological activity

Darbepoetin alfa is a re-engineered form of erythropoietin containing 5 amino acid changes (N30, T32, V87, N88, T90) resulting in the creation of 2 new sites for N-linked carbohydrate addition. It has a 3-fold longer serum half-life compared to epoetin alpha and epoetin beta. It stimulates erythropoiesis (increases red blood cell levels) by the same mechanism as rHuEpo (binding and activating the Epo receptor) and is used to treat anemia, commonly associated with chronic kidney failure and cancer chemotherapy