Comparison of the pharmacodynamic profiles of a biosimilar filgrastim and Amgen filgrastim: results from a randomized, phase I trial

Abstract

Further to the patent expiry of Neupogen (Amgen filgrastim), Hospira has developed a biosimilar filgrastim (Nivestim) that may offer a clinically effective alternative for multiple hematologic and oncologic indications. Here results are reported from a phase I trial, primarily designed to compare the pharmacodynamic profiles of Hospira filgrastim and Amgen filgrastim. A phase I, single-center, double-blind, randomized trial was undertaken to demonstrate equivalence of the pharmacodynamic characteristics of Hospira filgrastim and Amgen filgrastim. Fifty healthy volunteers were randomized to receive 5 or 10 microg/kg dosing, before further randomization to treatment sequence. All volunteers received five daily subcutaneous doses of Hospira filgrastim or Neupogen, with subsequent crossover to the alternative treatment. Bioequivalence was evaluated by analysis of variance; if the estimated 90% confidence intervals (CIs) for the ratio of 'test' to 'reference' treatment means were within the conventional equivalence limits of 0.80-1.25, then bioequivalence was concluded. Forty-eight volunteers completed the study. Geometric mean absolute neutrophil count area under the curve from time 0 to the last time point at day 5 (primary endpoint) was comparable in volunteers given Hospira filgrastim or Amgen filgrastim at 5 microg/kg (ratio of means, 0.98; 90% CI, 0.92-1.05) or 10 microg/kg (ratio, 0.97; 90% CI, 0.93-1.01); 90% CIs were within the predefined range necessary to demonstrate bioequivalence. Hospira filgrastim was well tolerated with no additional safety concerns over Amgen filgrastim. Hospira filgrastim is bioequivalent with Amgen filgrastim with regard to its pharmacodynamic characteristics.

Fig. 1

Study design and volunteer disposition. Superscript a All volunteers who received ≥1 dose of study medication; superscript b all volunteers who completed the study with a sufficient number of quantifiable concentrations to warrant parameter estimation in both assessment periods; superscript c all volunteers for whom an evaluable PD parameter was obtained in both assessment periods; superscript d volunteer withdrew

Fig. 2

Mean ANC over time in subjects given Hospira filgrastim or Amgen filgrastim; a 5-µg/kg dose group and b 10-µg/kg dose group. Data shown are geometric means. Samples taken outside each schedule timepoint window have been excluded. ANC absolute neutrophil count, AUC _0–tlast area under the curve from time 0 to the last time point, CI confidence interval

Fig. 3

Mean CD34+ cell count over time in subjects given Hospira filgrastim or Amgen filgrastim; a 5-µg/kg dose group and b 10-µg/kg dose group. Data shown are geometric mean values with lower and upper 95% confidence intervals