title: 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.
authors.affiliation: Medizinische Universitätsklinik, Freiburg, Germany. cornelius.waller@uniklinik-freiburg.de
authors.forename: Cornelius F
authors.initials: CF
authors.lastname: Waller
authors.forename: Miguel
authors.initials: M
authors.lastname: Bronchud
authors.forename: Stuart
authors.initials: S
authors.lastname: Mair
authors.forename: Rodeina
authors.initials: R
authors.lastname: Challand
mesh_terms: D000293:Adolescent; D000328:Adult; D019540:Area Under Curve; D018592:Cross-Over Studies; D005260:Female; D000069585:Filgrastim; D016179:Granulocyte Colony-Stimulating Factor / Q000009:adverse effects / Q000493:pharmacokinetics* / Q000627:therapeutic use*; D006402:Hematologic Diseases / Q000188:drug therapy; D006801:Humans; D008297:Male; D008875:Middle Aged; D009369:Neoplasms / Q000188:drug therapy; D011994:Recombinant Proteins; D013810:Therapeutic Equivalency; D055815:Young Adult
chemical_list: D011994:Recombinant Proteins; D016179:Granulocyte Colony-Stimulating Factor; D000069585:Filgrastim