Biosimilar Pegfilgrastim-cbqv Demonstrated Similar Immunogenicity to Pegfilgrastim in Healthy Subjects Across Three Randomized Clinical Studies

Francesca Civoli, Barbara Finck, Helen Tang, Jennifer Hodge, Hillary O'Kelly, Vladimir Vexler, Francesca Civoli, Barbara Finck, Helen Tang, Jennifer Hodge, Hillary O'Kelly, Vladimir Vexler

Abstract

Introduction: Biologic therapeutics can trigger immune responses in patients. As part of the totality of evidence that is required for regulatory approval of biosimilars, immunogenicity similarity must be assessed in the clinical programs. Pegfilgrastim-cbqv (UDENYCA®) is a pegfilgrastim biosimilar approved in the USA and European Union. This article demonstrates the similar immunogenicity of pegfilgrastim-cbqv compared with its reference product, pegfilgrastim (Neulasta®).

Methods: The immunogenicity of pegfilgrastim-cbqv was assessed in three clinical studies in healthy subjects (one specifically designed to evaluate immunogenicity similarity and two studies to assess pharmacokinetics and pharmacodynamics bioequivalence) using a tiered approach, in which plasma samples were tested for the presence of antidrug antibodies (ADAs) as well as ADA binding-specificity, titer and neutralizing activity. To assess the clinical impact of ADAs, pharmacokinetics, pharmacodynamics and safety profiles were compared between ADA-positive and -negative subjects.

Results: These studies demonstrated similar immunogenicity of pegfilgrastim-cbqv and pegfilgrastim. The small differences in ADA incidence between treatment groups observed in the immunogenicity study were driven by non-neutralizing, low-titer, polyethylene glycol (PEG)-reactive ADAs, which are commonly present in healthy subjects. No treatment-emergent neutralizing antibodies (NAbs) were detected in either treatment group, and there was no apparent impact of ADAs on pharmacokinetics, pharmacodynamics or safety.

Conclusion: Pegfilgrastim-cbqv has similar immunogenicity to pegfilgrastim. The presented immunogenicity, pharmacokinetics, pharmacodynamics and safety data support the overall demonstration of no clinically meaningful differences between pegfilgrastim-cbqv and pegfilgrastim.

Clinical trial registration: NCT02418104 (CHS-1701-04, April 2015), NCT02650973 (CHS-1701-05, February 2016) and NCT02385851 (CHS-1701-03, March 2015).

Keywords: Biosimilar; Febrile neutropenia; G-CSF; Immunogenicity; Pegfilgrastim; UDENYCA.

© 2022. The Author(s).

Figures

Fig. 1
Fig. 1
Study schematics. aIn study CHS-1701-04, 303 subjects were randomized and evaluated for safety. Due to protocol deviation (some subjects receiving the incorrect dose 2), a total of 268 subjects were included in the ADA analyses. ADA antidrug antibody
Fig. 2
Fig. 2
Schematic of tiered immunogenicity assay approach. aApplies to study CHS-1701-04 only. ADA antidrug antibody; G-CSF granulocyte-colony stimulating factor; NAb neutralizing antibody; PEG polyethylene glycol
Fig. 3
Fig. 3
Comparison of the PK parameters aCmax and b AUC0-last between ADA-negative subjects and subjects with treatment-emergent ADA across all periods in study CHS-1701-04. The geometric means are represented by colored circles. Figure includes subjects with sufficient pharmacokinetics samples to calculate each parameter. ADA antidrug antibody, AUC0-last area under the plasma concentration-time curve calculated from time 0 to last measurable concentration, Cmax maximum plasma concentration, PK pharmacokinetics, TE treatment-emergent
Fig. 4
Fig. 4
Comparison of the PD parameters a ANCmax and b ANC AUC0-last between ADA-negative subjects and subjects with treatment-emergent ADA across all periods in study CHS-1701-04. The geometric means are represented by colored circles. ADA antidrug antibody, AUC0-last area under the plasma concentration-time curve calculated from time 0 to last measurable concentration, ANCmax maximum observed absolute neutrophil count, TE treatment emergent

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