title: Safety and Biosimilarity of ior®LeukoCIM Compared to Neupogen®Based on Toxicity, Pharmacodynamic, and Pharmacokinetic Studies in the Sprague-Dawley Rat.
abstract: This study examined the safety, pharmacodynamic and pharmacokinetic similarity of the human recombinant filgrastim products ior®LeukoCIM and Neupogen®following a 28-day repeated subcutaneous dose administration in male and female Sprague-Dawley rats with a 14-day recovery period. Safety profiling was based on clinical observations, clinical pathology, and pathology findings for control rats dosed with vehicle and rats dosed either with 15, 75, and 150 μg/kg of ior®LeukoCIM or with 150 μg/kg of Neupogen®. The major adverse treatment-related clinical finding was mild to severe swelling of the hock-joint (tarsal joint) and hind limb, alone or accompanied with lameness which was more prominent in males and which had a similar frequency of occurrence for both ior®LeukoCIM and Neupogen®. All adverse findings were fully reversible. As expected, ior®LeukoCIM and Neupogen®both increased white blood cell and neutrophil levels in rats and to a similar extent for high-dose ior®LeukoCIM and Neupogen®. The pharmacokinetics of filgrastim following dosing with ior®LeukoCIM were well behaved and comparable for high-dose ior®LeukoCIM and Neupogen®. The results of this study imply that ior®LeukoCIM and Neupogen®had similar safety profiles, pharmacodynamic responses, and pharmacokinetic profiles that suggest they are biosimilar.
authors.affiliation: Nucro-Technics, 2000 Ellesmere Road, Unit 16, Toronto, Ontario, Canada M1H 2W4.
authors.forename: Albert
authors.initials: A
authors.lastname: Licollari
authors.affiliation: Nucro-Technics, 2000 Ellesmere Road, Unit 16, Toronto, Ontario, Canada M1H 2W4.
authors.forename: Katherine
authors.initials: K
authors.lastname: Riddle
authors.affiliation: Nucro-Technics, 2000 Ellesmere Road, Unit 16, Toronto, Ontario, Canada M1H 2W4.
authors.forename: Simon R
authors.initials: SR
authors.lastname: Taylor
authors.affiliation: Centre of Molecular Immunology, CIMAB S.A., Calle 206 #1926, esq. 21, Atabey, Playa, Cuba. Electronic address: Nuris@cim.sld.cu.
authors.forename: Nuris
authors.initials: N
authors.lastname: Ledon
authors.affiliation: Nucro-Technics, 2000 Ellesmere Road, Unit 16, Toronto, Ontario, Canada M1H 2W4.
authors.forename: Gordon T
authors.initials: GT
authors.lastname: Bolger
mesh_terms: D000818:Animals; D059451:Biosimilar Pharmaceuticals / Q000008:administration & dosage / Q000009:adverse effects* / Q000493:pharmacokinetics* / Q000494:pharmacology; D005260:Female; D000069585:Filgrastim / Q000008:administration & dosage / Q000009:adverse effects* / Q000493:pharmacokinetics* / Q000494:pharmacology; D006401:Hematologic Agents / Q000008:administration & dosage / Q000009:adverse effects* / Q000493:pharmacokinetics* / Q000494:pharmacology; D007958:Leukocyte Count; D008297:Male; D009504:Neutrophils / Q000166:cytology / Q000187:drug effects; D017207:Rats, Sprague-Dawley
chemical_list: D059451:Biosimilar Pharmaceuticals; D006401:Hematologic Agents; D000069585:Filgrastim
keywords: biosimilar; filgrastim; ior(®)LeukoCIM; pharmacodynamic; pharmacokinetic; safety