No abstract

Background: HX575 is a human recombinant epoetin alfa that was approved for use in Europe in 2007 under the European Medicines Agency biosimilar approval pathway. Therefore, in order to demonstrate the bioequivalence of HX575 to an existing epoetin alfa, the pharmacokinetic and pharmacodynamic response to steady state circulating concentrations of HX575 and a comparator epoetin alfa were compared following multiple intravenous administrations.

Background: Recombinant human epoetin alfa, HX575, is the first biosimilar erythropoiesis-stimulating agent (ESA) with European marketing authorisation. The primary objective of this double-blind, randomised, multicentre study was to assess the efficacy and safety of HX575 in treating chemotherapy-associated symptomatic anaemia in patients with solid tumours. Patients and Methods: The patients (n = 114) were treated with HX575 or active control (epoetin alfa) at 150 IU/kg body weight 3 times weekly for 12 weeks, increased to 300 IU/kg body weight 3 times weekly if the haemoglobin/reticulocyte increase was insufficient after 4 or 8 weeks. Results: With HX575, haemoglobin increased by ≥20 g/l in 62% (37/60 patients). The confidence interval (48.2%, 73.9%) was entirely above the pre-defined 30% threshold. Both groups showed similar results for safety profiles and secondary efficacy parameters. Transfusion requirements were 32% (19/60) (HX575) and 38% (13/34) (epoetin alfa). Conclusions: In treating chemotherapy-associated symptomatic anaemia in patients with solid tumours, the biosimilar ESA, HX575, is efficacious with a safety profile as expected for the therapeutic area.

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 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.

No abstract