Bioequivalence of HX575 (recombinant human epoetin alfa) and a comparator epoetin alfa after multiple subcutaneous administrations

Abstract

Aim: To compare the steady-state pharmacokinetics and pharmacodynamics (PK/PD) of two erythropoesis-stimulating agents (ESA), HX575 (Binocrit®, 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 AUECHb (98.9% [97.7-100.2%]), the primary PD endpoint. The PK of the two treatments were also similar as shown by the AUC0-48 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 © 2008 S. Karger AG.