title: Pharmacokinetic and pharmacodynamic profile of new biosimilar filgrastim XM02 equivalent to marketed filgrastim Neupogen: single-blind, randomized, crossover trial.
abstract: OBJECTIVE
  Filgrastim XM02 is a biosimilar non-glycosylated recombinant methionyl form of human granulocyte colony-stimulating factor (r-MetHuG-CSF) expressed in Escherichia coli for subcutaneous and intravenous administration in the treatment of different forms of neutropenia and stem cell mobilization. This study was conducted to compare the pharmacokinetic and pharmacodynamic characteristics of the new biosimilar filgrastim XM02 with the marketed filgrastim (Neupogen).
  
  
  METHODS
  Two filgrastim doses (5 and 10 microg/kg) of the new biosimilar filgrastim XM02 and the marketed filgrastim were administered either as intravenous infusion or subcutaneous injection in four single-dose, crossover, randomized substudies, conducted in 36 subjects each. Serum concentrations of filgrastim were determined using an enzyme-linked immunosorbent assay test kit on samples taken at intervals up to 48 hours after administration. The CD34+ stem cell count up to 15 days after administration was determined by flow cytometry using a validated CD34+ cell enumeration kit, and the absolute neutrophil count (ANC) up to 96 hours after dosing was determined by the Beckman Coulter AcT differential automated hematology analyzer. The primary pharmacokinetic endpoint was the AUC (48 h) (area under the serum concentration-time curve) of filgrastim serum concentration determined by the linear trapezoidal rule. Equivalence (biosimilarity) between the two filgrastim products was assessed by 90% confidence limits obtained from analyses of variance of log-transformed pharmacokinetic and pharmacodynamic endpoints, applying 80-125% equivalence intervals.
  
  
  RESULTS
  The mean serum concentration profiles of filgrastim, ANC and CD34+ cells over time were similar for the two filgrastims. The 90% confidence intervals for all test/reference ratios for pharmacokinetic and pharmacodynamic endpoints lay within the accepted bioequivalence range of 80-125%. Both filgrastims showed similar safety profiles and were well tolerated.
  
  
  CONCLUSIONS
  Equivalence of the two filgrastims was clearly demonstrated for all four dose/route of administration groups. Equivalence could be demonstrated for the serum concentration profile, for the ANC profile and, even more importantly, for the CD34+ cell count, which is a marker for the ability of the granulocyte colony-stimulating factor to mobilize stem cells.
authors.affiliation: BioGeneriX AG, Mannheim, Germany. heinz.lubenau@t-online.de
authors.forename: Heinz
authors.initials: H
authors.lastname: Lubenau
authors.forename: Peter
authors.initials: P
authors.lastname: Bias
authors.forename: Anne-Katrin
authors.initials: AK
authors.lastname: Maly
authors.forename: Karl Ernst
authors.initials: KE
authors.lastname: Siegler
authors.forename: Kai
authors.initials: K
authors.lastname: Mehltretter