Pegfilgrastim biosimilars – PEGylation is a mature and versatile platform for improving biopharmaceutical performance

As of December 31, 2025, the U.S. Food and Drug Administration (FDA) has approved seven biosimilars for pegfilgrastim, the active ingredient in the reference product Neulasta (developed by Amgen). Pegfilgrastim is a PEGylated form of granulocyte colony-stimulating factor used to reduce the risk of febrile neutropenia in patients undergoing myelosuppressive chemotherapy. These biosimilars enhance access to supportive care in oncology by offering cost-effective alternatives while maintaining comparable efficacy and safety profiles to the reference product.

The approved pegfilgrastim biosimilars

• Fulphila (pegfilgrastim-jmdb) – Developed by Biocon/Mylan
• Udenyca (pegfilgrastim-cbqv) – Developed by Coherus BioSciences/Accord
• Ziextenzo (pegfilgrastim-bmez) – Developed by Sandoz
• Nyvepria (pegfilgrastim-apgf) – Developed by Pfizer
• Fylnetra (pegfilgrastim-pbbk) – Developed by Amneal/Kashiv
• Stimufend (pegfilgrastim-fpgk) – Developed by Fresenius Kabi
• Armlupeg (pegfilgrastim-unne) – Developed by Lupin Limited (approved November 28, 2025)

Pegfilgrastim biosimilars in development

Market analyses from 2024–2025 estimate over 15 pegfilgrastim biosimilars in various stages of development worldwide, driven by patent expirations, increasing demand for cost-effective supportive oncology care, and expansions into emerging markets. Specific candidates mentioned in pipeline overviews include variants such as MK-6302, Peg G-CSF, Grasustek, LA-EP2006 (some of which may correspond to approved or previously developed products), R-TPR-029, and other filgrastim/PEG-GCSF derivatives. These developments focus on improved delivery systems (e.g., on-body injectors), enhanced formulations for patient convenience, and broader accessibility in regions with growing biosimilar adoption, such as Asia and Latin America. Ongoing research also explores extended-release or novel administration options, though no major new U.S. approvals beyond Armlupeg have been reported in late 2025. This pipeline activity supports projected market growth, with the global pegfilgrastim biosimilars sector anticipated to expand significantly through 2030–2035 due to sustained innovation and regulatory support for abbreviated pathways.

glycoPEGylation – Lipegfilgrastim

Lipegfilgrastim, marketed under the brand name Lonquex, is a long-acting, recombinant granulocyte colony-stimulating factor (G-CSF) developed for the prophylaxis of chemotherapy-induced neutropenia. It is indicated for reducing the duration of neutropenia and the incidence of febrile neutropenia in adult patients receiving cytotoxic chemotherapy for malignancy (excluding chronic myeloid leukemia and myelodysplastic syndromes). Lipegfilgrastim is a glycoPEGylated form of filgrastim (recombinant human G-CSF). It employs site-specific glycoPEGylation technology, where a 20 kDa polyethylene glycol (PEG) moiety is attached via a sialic acid derivative to an O-glycan at threonine 134 on the G-CSF molecule. This modification prolongs the drug’s half-life by reducing renal clearance while maintaining binding affinity to the G-CSF receptor. Like pegfilgrastim, it stimulates the proliferation, differentiation, and activation of neutrophils in the bone marrow, enhancing antibacterial activity and reducing infection risk during myelosuppressive therapy. Compared to pegfilgrastim (which features direct PEG attachment to the N-terminal methionine), lipegfilgrastim exhibits greater resistance to degradation by neutrophil elastase and potentially improved pharmacokinetic stability.

Lipegfilgrastim received marketing authorization from the European Medicines Agency (EMA) in July 2013 and is available in the European Union and select other regions. As of December 30, 2025, it is not approved by the U.S. Food and Drug Administration (FDA) and remains unavailable in the United States. Phase III randomized trials have demonstrated that lipegfilgrastim (6 mg fixed dose, administered subcutaneously once per chemotherapy cycle) is non-inferior to pegfilgrastim in reducing the duration of severe neutropenia, with comparable incidences of febrile neutropenia and similar safety profiles. Studies in breast cancer and non-small cell lung cancer patients showed efficacy superior to placebo and equivalent to pegfilgrastim, with some secondary endpoints (e.g., time to absolute neutrophil count recovery) favoring lipegfilgrastim. Common adverse effects include bone pain, musculoskeletal pain, and headache, consistent with the G-CSF class. This agent represents an advancement in PEGylation strategies through glycoPEGylation, offering a once-per-cycle dosing regimen that enhances patient convenience in supportive oncology care where approved.

Non-PEGylated or Alternative G-CSFs

Short-acting G-CSFs require daily administration but are effective alternatives, particularly when single-dose long-acting options are not preferred. Filgrastim (Neupogen) and its biosimilars, such as Zarxio (filgrastim-sndz), Nivestym (filgrastim-aafi), Releuko (filgrastim-ayow), and Granix (tbo-filgrastim). Lenograstim (available in some regions outside the U.S.; similar to filgrastim).

Long-acting non-PEGylated alternatives include Efbemalenograstim alfa (Ryzneuta; FDA-approved in 2023) — a dimeric Fc-fusion protein G-CSF that provides sustained neutrophil support without PEGylation. Phase III trials demonstrated noninferiority to pegfilgrastim in duration of severe neutropenia, with comparable safety.

Consult Creative PEGWorks for your protein PEGylation needs.