Abstract
Background
Recombinant human erythropoietin (epoetin) has been in use for the treatment of different types of anemia for decades. Hemax® contains epoetin alfa developed and marketed in Argentina since 1990. In the forthcoming years, Hemax® reached market in several developing countries in Latin America, Africa and Asia. Originally, Hemax® presented as lyophilized powder with albumin, and recently, also as prefilled syringes without albumin. The advent of the biosimilar regulations determined the need to perform additional comparative studies and allowed also to compare the possible impact of lyophilization and albumin on epoetin alfa pharmacology. In this report we present the comparative PK/PD study of both Hemax® formulations as well as the comparison with the innovator epoetin alfa product.
Methods
Relative bioavailability study on 24 healthy subjects, with measurement of reticulocytes as PD marker, comparing 3 formulations of epoetin alfa, at 40,000 IU strength by SC route: Hemax® (Biosidus) vial (lyophilized, with albumin), Hemax® NF (Biosidus) prefilled syringe (liquid, without albumin) and Eprex® (Janssen-Cilag) prefilled syringe (liquid, without albumin). Plasma erythropoietin was measured by chemiluminescent immunoassay (Immulite®, Siemens). Reticulocytes were measured by flow cytometry (FacsScan®, Becton-Dickinson, with CellQuest® analysis). Equivalence analysis was performed with WinNonLin.
Results:
Comparison of both prefilled syringes showed Hemax NF® to be bioequivalent to Eprex®: the Hemax®/Eprex® ratio for Cmax was 95.03 % (90%CI 84.70-106.61 %) and for AUC(0-120 h) 90.31 % (90%CI 82.09-99,36 %); for the geometric mean of AUC(0-inf) the ratio was 95.42 %. (90%CI 87.23 -104.37 %). Lyophilization and the presence of albumin did not seem to impact significantly the kinetics of epoetin, since both formulation of Hemax® were bioequivalent: the ratio Hemax® NF/Hemax® for geometric means of Cmax was 106.98 % (90%CI= 95.18-120.24 %); for AUC(0-120 h) was 108.49 % (90%CI 98.45-119.54 %) and for AUC(0-inf) 111.30 % (90%CI 101.30-121.92 %). As to reticulocytes, the 3 products behave similarly; the ratio Hemax® NF/Eprex® for peak reticulocyte count was 93.27 % (90%C 85.98-101.17 %) and for Hemax® NF/Hemax® 95.00 % (90%CI 87.48-103.16 %).
Conclusions: Hemax® NF is bioequivalent to Eprex®. Lyophilization and presence of albumin as stabilizer do not affect significantly PK/PD properties of Hemax®.
