Pegfilgrastim-Fpgk Shows Structural, Functional Biosimilarity to Reference Product

Results of a study showed robust evidence supporting the structural and functional biosimilarity between pegfilgrastim-fpgk (Stimufend; Fresenius Kabi) and pegfilgrastim (Neulasta; Amgen).¹

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According to the Mayo Clinic, pegfilgrastim is indicated to treat neutropenia that is caused by cancer medications and helps the bone marrow to create new white blood cells. It can help reduce the risk of infection and improve survival in patients exposed to radiation due to cancer.²

Currently, there are 6 biosimilars either approved or in development for pegfilgrastim in the US, with 11 others approved in outside the US. The study authors note that the benefits of biosimilar pegfilgrastim include lower costs, fewer health care visits, and expanded treatment and administration options. They aimed to determine the analytical similarity of pegfilgrastim-fpgk to the reference product because the safety, immunogenicity, pharmacokinetics, and pharmacodynamic equivalence has already been established.¹

Twenty-eight lots of US- and EU-licensed pegfilgrastim were compared with 16 lots of pegfilgrastim-fpgk, according to the study authors. In the comparative analysis, the primary structure was assessed using peptide mapping by liquid chromatography mass spectrometer in reduced condition, amino acid analysis, intact mass by matrix-assisted laser desorption ionization time-of-flight, and polydispersity with liquid chromatography mass spectrometry. The purities and impurities were also evaluated with size-exclusion high-performance liquid chromatography, analytical ultracentrifugation, and size-exclusion chromatography-multi-angle laser light scattering. Product variants, composition and content, and biological activity were also measured.¹

According to the results, both the biosimilar and the reference product were identical in the primary sequence, including post-translational modification levels, mPEG attachment site, molar absorptivity, and polydispersity. Additionally, the investigators reported that the higher order structure was comparable between the 2 products.¹

With regard to purity, the biosimilar showed similar aggregated/monomeric content, size heterogeneity, sub-visible particles per mL, free granulocyte colony-stimulating factor, and mPEG content, compared with the reference product. Further, the electrophoretic mobility and purity were similar between pegfilgrastim-fpgk and pegfilgrastim.¹

However, the investigators noted that the biosimilar did show a higher percentage of monomer, indicating fewer impurities compared with the reference product, with 36% and 45% falling within the QR, respectively. Lower levels of residual mPEG were also detected in the biosimilar, suggesting an overall lower impurity profile compared with pegfilgrastim.¹

For content, the assessment showed that 100% of the extractable volume and total extractable protein content were within the QR for both drugs, which was confirmed by evaluating the protein concentration further and is recommended by the FDA. According to the study authors, there were no clinically significant differences between either pegfilgrastim-fpgk or pegfilgrastim, which confirmed the approval of the biosimilar by the FDA and the European Medicines Agency.¹

In September 2022, the FDA approved pegfilgrastim-fpgk to reduce the incidence of infection due to febrile neutropenia for patients undergoing chemotherapy. The approval was based on a review of a data package and a totality of evidence that showed the similarity of the biosimilar with pegfilgrastim, which demonstrated no clinically meaningful differences in safety or immunogenicity.³

REFERENCES

1. Sykes A, Ingram L, Kronthaler U, Chevalet L. Demonstration of physicochemical and functional similarity between Stimufend (pegfilgrastim-fpgk) and Neulasta (pegfilgrastim): A comparative analytical assessment. PLoS One. 2024;19(10):e0309480. Published 2024 Oct 24. doi:10.1371/journal.pone.0309480

2. Mayo Clinic. Pegfilgrastim (subcutaneous route). February 1, 2024. Accessed November 1, 2024. https://www.mayoclinic.org/drugs-supplements/pegfilgrastim-subcutaneous-route/description/drg-20066866

3. Antrim A. FDA Approves Stimufend, Biosimilar for Pegfilgrastim-fpgk. Pharmacy Times. September 7, 2022. Accessed November 1, 2024. https://www.pharmacytimes.com/view/fda-approves-stimufend-biosimilar-for-pegfilgrastim-fpgk