Hematide is immunologically distinct from erythropoietin and corrects anemia induced by antierythropoietin antibodies in a rat pure red cell aplasia model

Objective To evaluate the potential of Hematide, a PEGylated, synthetic peptide–based erythropoiesis-stimulating agent that is in clinical development for the treatment of anemia associated with chronic kidney disease and cancer, to correct antierythropoietin antibody–associated pure red cell aplasia (PRCA). Materials and Methods The binding of anti-Hematide antibodies (mouse, rabbit, and monkey) to recombinant human erythropoietin (rHuEPO) and of anti-rHuEPO antibodies (mouse, goat, rat, and human) to Hematide were evaluated. An anti-EPO antibody–mediated anemia rat model was developed by subcutaneously administering rHuEPO to rats three times weekly for 4 weeks. Sixty percent of the animals developed PRCA as characterized by severe anemia, reduced reticulocytes, anti-EPO antibodies, and limited bone marrow erythroid precursors. The effect of Hematide administration on the PRCA rats was evaluated. Results Antibodies to EPO do not cross react with Hematide and, conversely, antibodies to Hematide do not cross react with EPO. Hematide corrected antibody-induced anemia in a rat PRCA model. Conclusions The data support the potential of Hematide to correct anti-EPO antibody–associated PRCA in humans. In addition, the data suggest a negligible risk for development of anti-EPO antibody–induced PRCA secondary to Hematide administration.