Preclinical and clinical phase I studies of a new recombinant Filgrastim (BK0023) in comparison with Neupogen®

BMC Clinical Pharmacology

Andrea Di Stefano¹  Gaetano Orsini²  Simona Dedoni³  Pierluigi Onali³  Gloria Saccani Jotti⁴  Giancarlo Tonon²  Rodolfo Schrepfer²  Gaia Spinetti⁵  Davide Crobu² 

[1] CROSS Research S.A, Phase I Unit, via F. A. Giorgioli 14, CH-6864 Arzo, Switzerland;Bio-Ker S.r.l.-Multimedica Group, Sardinia Scientific and Technological Park, Building 3, I-09010 Pula Cagliari, Italy;Department of Biomedical Sciences, Laboratory of Cellular and Molecular Pharmacology, University of Cagliari, 09042 Monserrato Cagliari, Italy;Department of Biomedical, Biotechnological and Traslational Science (S.Bi.Bi.T.), University of Parma, via Volturno 39, 43121 Parma, Italy;IRCCS MultiMedica, Laboratory of Diabetological Research, Milan, Italy

关键词: Comparability;    Biosimilar Filgrastim;    BK0023;    r-Met-G-CSF;   

Others  :  860413
DOI  :  10.1186/2050-6511-15-7

 received in 2013-07-24, accepted in 2014-02-01,  发布年份 2014

【 摘 要 】

Background

Filgrastim or methionyl-granulocyte colony-stimulating factor (Met-G-CSF), is a recombinant therapeutic protein widely used to treat severe neutropenia caused by myelosuppressive drugs in patients with nonmyeloid malignancies. In addition to its role in the regulation of granulopoiesis, treatment with G-CSF is considered the standard approach to mobilize CD34 positive (CD34⁺) mononuclear cells for reconstituting hemopoietic ability for bone marrow transplantation. An intended biosimilar filgrastim (coded BK0023) was produced in GMP conditions by E.coli fermentation according to an original recombinant process and showed physico-chemical properties and purity profile similar to Neupogen^®, a commercial preparation of filgrastim. The aim of the present study was to demonstrate the comparability of BK0023 to Neupogen^® in terms of both in vitro biological activities and in vivo toxicology, pharmacokinetics and pharmacodynamics.

Methods

Cell proliferation and radioligand binding assays were conducted in NFS-60 cells to compare the biological activity and functional interaction with the G-CSF receptor in vitro, while preclinical in vivo studies, including pharmacokinetics and pharmacodynamics after repeated dose were performed in normal and neutropenic rats. A phase I study was carried out in healthy male volunteers treated by multiple-dose subcutaneous administration of BK0023 and Neupogen^® to evaluate their pharmacodynamic effects as well as their pharmacokinetic and safety profile and to demonstrate their pharmacodynamic equivalence and pharmacokinetic bioequivalence.

Results

The results reported in this work demonstrate that BK0023 is comparable in terms of biological activity, efficacy and safety to Neupogen^®.

Conclusions

BK0023 has the same pharmacokinetic profile, efficacy and safety as the reference commercial filgrastim Neupogen^® and therefore could be further developed to become a convenient option to treat neutropenia in oncological patients.

Trial registration

Trial registration number (TRN): NCT01933971. Date of registration: Sept 6th 2013.

【 授权许可】

   
2014 Crobu et al.; licensee BioMed Central Ltd.

【 图 表 】

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