pegfilgrastim case study for 7 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.

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, 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. 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.

Pegfilgrastim is a sustained-duration form of filgrastim, a recombinant methionyl form of human granulocyte colony-stimulating factor (G-CSF), to which a 20 kDa polyethylene glycol molecule is covalently bound to the N-terminal methionine residue. Similar to filgrastim, pegfilgrastim increases the proliferation and differentiation of neutrophils from committed progenitor cells, induces maturation, and enhances the survival and function of mature neutrophils, resulting in dose-dependent increases in neutrophils.

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.

Glycan targeted PEGylation is a unique strategy for site-specific PEG attachment to proteins. A general strategy schematic is shown below.

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

PEGylation is the process of covalent and non-covalent attachment or fusion of PEG polymer chains to molecules and macrostructures. The PEGylated structures result in improved solubility, enhanced molecular stability, and a slowing down of its degradation as well as elimination in vivo, making them more effective for many therapeutic applications.

At Creative PEGWorks, we provide generic or site-specific PEGylation of proteins, antibodies, aptamers, DNAs, small molecules, dendrimers, nanoparticles, and biodegradable polymers. We also can provide post-translational polysaccharide modification of biologics, protein lipidation, bioconjugation, and crosslinking chemistry.

At Creative PEGWorks, we offer the flexibility to utilize our high-quality PEGs or create custom PEG products, ensuring a personalized solution for your project. With our PEGylation Service Model 1, you can entrust us with delivering PEGylated proteins, peptides, oligonucleotides, DNA, RNA, or small molecules.

At Creative PEGWorks, we offer an array of specialized services to meet your PEGylation needs and provide you with valuable insights for your preclinical stages.

We begin by screening a range of high-quality PEG derivatives, carefully selecting the ones that best suit your project requirements.

Through rigorous experimentation, we:
– Identify the ideal PEGylation reaction conditions and develop robust processes for purification.
– Focus on analytical method development to ensure accurate characterization of your PEGylated compounds.
– Provide you with a detailed report, encompassing the PEGylation reaction conditions, separation and purification processes, and comprehensive analytical methods for your PEGylated compounds.
– Synthesize, characterize, and deliver the PEGylated molecule to you for pharmaceutical analysis.

Building on the success of Phase 1, Creative PEGWorks collaborates with partner Contract Research Organizations (CROs) to facilitate IND (Investigational New Drug) enabling preclinical study data for your PEGylated compounds. This phase aims to determine the optimal PEGylated compounds for your specific application.

Our PEGylation service includes:
– Conducting a thorough quality specification study of the PEGylated molecules.
– Exploring formulation strategies for enhanced stability.
– Performing pharmacokinetics and pharmacodynamics (PK/PD) studies to assess the compound’s behavior in vivo.
– Conducting essential toxicology studies to evaluate the safety profile of the PEGylated molecules.
– Assisting in the IND filing process with the FDA, EU and other government agencies, ensuring regulatory compliance.