Bioequivalence of HX575 (Recombinant Human Epoetin Alfa) and a Comparator Epoetin Alfa after Multiple Subcutaneous Administrations

Aim: To compare the steady-state pharmacokinetics and pharmacodynamics (PK/PD) of two erythropoesis-stimulating agents (ESA), HX575 (Binocrit (R), Sandoz GmbH, Holzkirchen, Germany), human recombinant epoetin alfa approved as the first biosimilar ESA, and a comparator epoetin alfa, following multiple subcutaneous administrations. Methods: An open, randomized, parallel group study was conducted in 80 healthy adult males. Subjects were randomized to multiple subcutaneous doses of 100 IU/kg body weight of HX575 or of the comparator epoetin alfa 3 times weekly for 4 weeks. Results: The hematological profiles of both treatments were similar, as determined from the population mean curves and area under the effect curve ( AUEC)ratios. HX575 met the predefined biosimilarity criteria with respect to the ratio and 90% confidence interval of the AUEC(Hb) (98.9% [97.7-100.2%]), the primary PD endpoint. The PK of the two treatments were also similar as shown by the AUC(0-48) ratios and 90% confidence intervals, 94.3% [84.7-105.0%] and 96.9% [88.2-106.5%], respectively. Study medication was well tolerated and neutralizing anti-epoetin antibodies were not detected. Conclusions: HX575 and the comparator epoetin alfa were bioequivalent with respect to their PK/PD, supporting the conclusion that both, when administered subcutaneously, will be equally efficacious and may be interchangeable as therapy. Copyright (C) 2008 S. Karger AG, Basel