Pharmacokinetic and pharmacodynamic properties of a new biosimilar filgrastim TPI G-CSF in comparison to the marketed reference filgrastim Neupogen^®: a double-blind, single-dose, two-period crossover trial

Abstract:

Biosimilar biological products are a safe and effective alternative to branded biological agents. One of the most common uses of the therapeutic protein filgrastim, a biological drug (recombinant human granulocyte-colony stimulating factor), is to reduce the occurrence and duration of severe neutropenia and its associated serious complications. TPI G-CSF, a filgrastim product under development by Therapeutic Proteins International, LLC, is a proposed biosimilar to Amgen’s marketed filgrastim, Neupogen^®. To evaluate bioequivalence, we conducted a double-blind, randomized, two-period crossover study that took place at a single center and had a washout period of at least 2 weeks. The pharmacokinetic endpoints (area under the concentration-time curve from time 0 to time of the last observed/measured non-zero concentration [AUC_0-t], AUC from time 0 extrapolated to infinity [AUC_0-inf], and maximum observed concentration [C_max]) and the pharmacodynamic endpoints (baseline-corrected area under the effect curve from time zero to the last non-zero cell count data [AUEC_0-t] and maximum observed effect [E_max]) for the absolute neutrophil count were compared after administration of a subcutaneous 5 μg/kg dose of TPI G-CSF or Neupogen^® in 58 healthy adults. These 58 healthy subjects (72% male, 34.8±10.5 years, 77.1±14.1 kg) were randomly assigned to a treatment sequence group (TPI G-CSF-Neupogen^® or Neupogen^®-TPI G-CSF); subjects received a single subcutaneous injection of 5 μg/kg in each period. The 95% pharmacodynamic and 90% pharmacokinetic geometric confidence intervals of the ratio (TPI G-CSF/Neupogen^®) of least-squares means from the analysis of variance of the natural log-transformed data for each parameter fell within the approved bioequivalence range of 80% to 125%. There were no serious adverse events in this study. Treatment-emergent adverse events were reported by 69% of the study subjects, with a similar incidence between treatments. The notable incidents were treatment-emergent injection site reactions. Injections of TPI G-CSF and Neupogen^® appeared to be safe and equally well tolerated.

Keywords::

• filgrastim
• G-CSF
• pharmacokinetic
• pharmacodynamic
• ANC
• WBC

Acknowledgments

The author thanks Sherri D Jones, PharmD, of Pharma Write, LLC, for providing medical writing and editorial assistance. This manuscript was prepared according to the International Society for Medical Publication Professionals’ “Good Publication Practice for Communicating Company-Sponsored Medical Research: The GPP2 Guidelines.”

Disclosure

Sarfaraz K Niazi is an employee of Therapeutic Proteins International, LLC and the described research was funded by Therapeutic Proteins International, LLC. The author reports no other conflicts of interest.