Development of a new G-CSF product based on biosimilarity assessment

Abstract

BackgroundZarzio®, a new recombinant human granulocyte colony-stimulating factor (filgrastim), was evaluated in healthy volunteers and neutropenic patients in phase I and III studies. Patients and methodsHealthy volunteers in randomized, two-period crossover studies received single- and multiple-dose s.c. injections of 1 μg/kg (n=24), 2.5 μg/kg (n=28), 5 μg/kg (n=28), or 10 μg/kg (n=40), as well as single-dose i.v. infusions of 5 μg/kg (n=26), of Zarzio® or the reference product (Neupogen®). Filgrastim serum levels were monitored; pharmacodynamic parameters were absolute neutrophil count (all studies) and CD34+ cells (multiple-dose studies). Supportive efficacy and safety data were obtained from an open phase III study in 170 breast cancer patients undergoing four cycles of doxorubicin and docetaxel (Taxotere) chemotherapy, receiving Zarzio® (300 or 480 μg) as primary prophylaxis of severe neutropenia. ResultsThe results of the studies in healthy volunteers confirm the comparability of the test and reference products with respect to their pharmacodynamics and pharmacokinetics. Confidence intervals were within the predefined equivalence boundaries. In the phase III study in breast cancer patients, the administration of Zarzio® was efficacious and safe, triggering no immunogenicity. ConclusionThe results of these studies demonstrate the biosimilarity of Zarzio® with its reference product Neupogen®.