Bioequivalence of HX575 (recombinant human epoetin alfa) and a comparator epoetin alfa after multiple subcutaneous administrations.
OBJECTIVE
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 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.
Sörgel
Fritz
F
IBMP Institute for Biomedical and Pharmaceutical Research, Nurnberg, Germany. ibmp@osn.de
Thyroff-Friesinger
Ursula
U
Vetter
Andrea
A
Vens-Cappell
Bernhard
B
Kinzig
Martina
M
D000328:Adult; D000068817:Epoetin Alfa; D004921:Erythropoietin / Q000009:adverse effects* / Q000493:pharmacokinetics* / Q000494:pharmacology*; D006397:Hematinics / Q000009:adverse effects / Q000493:pharmacokinetics / Q000494:pharmacology; D006403:Hematologic Tests; D006454:Hemoglobins / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D007279:Injections, Subcutaneous; D008297:Male; D011994:Recombinant Proteins / Q000009:adverse effects / Q000493:pharmacokinetics / Q000494:pharmacology; D013810:Therapeutic Equivalency
D006397:Hematinics; D006454:Hemoglobins; D011994:Recombinant Proteins; D004921:Erythropoietin; D000068817:Epoetin Alfa