1496 - Randomized, double-blind, cross-over Phase I study comparing pharmacokinetics, pharmacodynamics, safety and immunogenicity of a biosimilar pegfilgrastim with EU and US references

Background

The pharmacokinetic (PK)/pharmacodynamic (PD), safety and immunogenicity profiles of Sandoz biosimilar pegfilgrastim (Ziextenzo®) and EU reference pegfilgrastim were shown to be similar in a pivotal phase I study. Similarity of efficacy and safety to the reference was demonstrated in two phase III studies in breast cancer patients receiving myelosuppressive chemotherapy. This 3-way study aimed to confirm similarity of PK/PD, safety and immunogenicity to US reference pegfilgrastim, and to bridge between the EU and US reference medicines.

Methods

This randomized, double-blind, 3-treatment, 6-sequence crossover phase I study included healthy volunteers (HVs) administered pegfilgrastim (biosimilar, EU reference, or US reference) once per treatment period. Primary objectives were to demonstrate PK similarity in AUC_0-inf, AUC_0-last and C_max, and PD similarity in ANC AUEC_0-last and ANC E_max. The study was powered (90%) to achieve confidence intervals within biosimilarity margins 0.8–1.25 in pairwise comparisons (biosimilar vs US reference, biosimilar vs EU reference, and US reference vs EU reference). Secondary objectives were safety, immunogenicity and additional PK/PD parameters.

Results

The study included 577 male and female HVs. PK and PD similarity were demonstrated for primary PK and PD parameters between Sandoz biosimilar, US reference, and EU reference (Table). The safety profile of Sandoz biosimilar pegfilgrastim was similar across groups. Incidence of antidrug antibodies was similar across groups (biosimilar: 31/512 [6.1%]; US reference: 36/511 [7.0%]; EU reference: 39/501 [7.8%]). Secondary PK/PD parameters were also similar.Table:

1815P Summary of PK and PD similarity

Conclusions

Sandoz biosimilar demonstrated similar PK/PD, safety, tolerability and immunogenicity to US reference and EU reference pegfilgrastim in this large 3-way crossover phase I study.

Clinical trial identification

EudraCT: 2016-003549-27.

Editorial acknowledgement

Caroline McGown of Spirit Medical Communications Ltd, supported by Hexal AG.

Legal entity responsible for the study

Hexal AG.

Funding

Hexal AG.

Disclosure

M. Velinova: Full / Part-time employment: PRA; Honoraria (self), compensation as lead Principal Investigator in the study: Sandoz Biopharmaceuticals. A. Bellon: Full / Part-time employment: Hexal AG. R. Nakov: Full / Part-time employment: Hexal AG. S. Schussler: Full / Part-time employment: Sandoz Inc. S. Schier-Mumzhiu: Full / Part-time employment: Hexal AG. C. Schelcher: Full / Part-time employment: Hexal AG. S.D. Koch: Full / Part-time employment: Hexal AG. A. Skerjanec: Full / Part-time employment: Novartis. J. Wang: Full / Part-time employment: Sandoz Inc. A. Krendyukov: Full / Part-time employment: Hexal AG. G.P. Otto: Full / Part-time employment: Hexal AG.