Preclinical evaluation reveals comparable toxicology and pharmacology of the erythropoietin biosimilar GBpoietin® and Eprex®

Erythropoietin (EPO) is an essential growth factor for erythropoiesis. We report the results of the preclinical safety evaluation of GBpoietin®, a recombinant human EPO (rhEPO), through a comparative acute toxicity study with the reference product, Eprex®. The products were administered subcutaneously into Wistar rats for both the single-dose and repeated-dose toxicity studies. Hematological and biochemical parameters were measured for all test subjects before the first dose and the day after the last dose in both studies. Necropsy and histopathology of representative subjects from each group were also performed to find any pathological changes, such as degeneration or cellular necrosis in internal organs such as the kidney, liver, lung, and spleen. Both GBpoietin® and Eprex® comparative toxicology studies, which were not significantly different (P > 0.05), revealed similar pharmacologically driven mechanisms of toxicity. Although hematological parameters stayed within the normal range throughout the study, improved profiles of hemoglobin and hematocrit (P < 0.05) confirmed the therapeutic effect of rhEPO in both studies. Moreover, the initial and final values of aspartate aminotransferase, alanine aminotransferase, and blood urea nitrogen were comparable (P > 0.05) for both experimental products. The study established that the toxicological profiles of GBpoietin® and Eprex® were similar and aligned with the known pharmacology of EPO alfa, demonstrating proof of “totality” and “no residual uncertainty.”