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Identification
- Summary
Lipegfilgrastim is a medication used to reduce the duration of chemotherapy-induced neutropenia and incidence of febrile neutropenia in cytotoxic chemotherapy.
- Generic Name
- Lipegfilgrastim
- DrugBank Accession Number
- DB13200
- Background
Lipegfilgrastim, previously known as XM22, is a pegylated, recombinant granulocyte colony-stimulating factor (G-CSF) that was synthetized using a highly site-specific glycoPEGylation technology 2. It is used as an alternate to Pegfilgrastim for prophylactic use in cancer patients receiving chemotherapy and at risk for developing chemotherapy-induced neutropenia. Since July 2013, lipegfilgrastim is marketed by the EMA as Lonquex for subcutaneously injection, where it is administered once following cytotoxic chemotherapy for each chemotherapy cycle in adult patients being treated with cytotoxic chemotherapy for malignancy. It aims to reduce the duration of neutropenia and the incidence of febrile neutropenia.
Neutropenia and febrile neutropenia (FN) are frequent and potentially fatal complications that occur from myelosuppressive anticancer treatments 2. Severe chemotherapy-induced neutropenia and febrile neutropenia significantly increases the risk for life-threatening infection and sepsis. Granulocyte colony-stimulating factors (G-CSFs) were introduced in the 1980's to the clinical setting to stimulate neutrophil proliferation and differentiation, thereby reducing the duration and severity of chemotherapy-induced neutropenia 2. Lipegfilgrastim is a covalent conjugate of Filgrastim with a single methoxy polyethylene glycol (PEG) molecule via a carbohydrate linker consisting of glycine, N-acetylneuraminic acid and N-acetylgalactosamine 5. The average molecular mass of lipegfilgrastim comprises 18,798 Da for Filgrastim, 203 Da for GalNAc, 338 Da for glycylsialic acid and approximately 20,000 Da for PEG 6. PEG moiety protects the active molecule from enzyme degradation, which allows longer half-life of drug and less frequent dosing-schedule in addition to acceptable safety and efficacy profile 2.
- Type
- Biotech
- Groups
- Approved, Investigational
- Biologic Classification
- Protein Based Therapies
Other protein based therapies - Protein Structure
- Protein Chemical Formula
- C866H1372N226O258S9*(C2H4O)n
- Protein Average Weight
- 39000.0 Da (glycoPEGylated, approximate)
- Sequences
>Lipegfilgrastim sequence MTPLGPASSLPQSFLLKCLEQVRKIQGDGAALQEKLCATYKLCHPEELVLLGHSLGIPWA PLSSCPSQALQLAGCLSQLHSGLFLYQGLLQALEGISPELGPTLDTLQLDVADFATTIWQ QMEELGMAPALQPTQGAMPAFASAFQRRAGGVLVASHLQSFLEVSYRVLRHLAQP
Download FASTA Format- Synonyms
- Lipegfilgrastim
- External IDs
- XM-22
- XM22
Pharmacology
- Indication
Indicated for the reduction in the duration of neutropenia and the incidence of febrile neutropenia in adult patients treated with cytotoxic chemotherapy for malignancy (with the exception of chronic myeloid leukaemia and myelodysplastic syndromes) 5.
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Indication Type Indication Combined Product Details Approval Level Age Group Patient Characteristics Dose Form Management of Febrile neutropenia •••••••••••• ••••• •••••••••• •••••••• Management of Neutropenia •••••••••••• ••••• •••••••••• •••••••• - Contraindications & Blackbox Warnings
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Mimicking endogenous granulocyte colony-stimulating factors, lipegfilgrastim enhances the number and function of circulating neutrophils by binding to endogenous G-CSF receptors. A small increase in monocyte and/or lymphocyte counts may also be observed 5. Following a single subcutaneous dose administration of 100 μg/kg, lipegfilgrastim resulted in a significant increase in neutrophilic granulocyte and large unstained cell counts 6. G-CSF also increases the antibacterial activities of neutrophils including the phagocytosis 5. Due to structural similarity between lipegfilgrastim and pegfilgrastim, G-CSF receptor binding was equivalent between two molecules 2. However, lipegfilgrastim showed greater time-dependent resistance to neutrophil elastase degradation and greater retention of activity than pegfilgrastim 2.
- Mechanism of action
Endogenous granulocyte colony-stimulating factor (G-CSF) is a glycoprotein that stimulates neutrophil progenitors. It is produced mainly by monocytes, fibroblasts and endothelial cells to promote the development of neutrophils and increase their proliferation and maturation 4. Subsequently, G-SCF stimulates the release of matured neutrophils from the bone marrow storage pools into the peripheral blood to enhance their function 5,4. Via binding to to the human G-CSF receptors, lipegfilgrastim activates the receptor signalling pathway as a growth factor to stimulate proliferation of haematopoietic progenitor cells and their differentiation into mature cells, and promote subsequent release into the peripheral blood 5. This stimulatory effect of lipegfilgrastim may extend to other single lineage and multilineage progenitors and pluripotent haematopoietic stem cells 5. The presence of the PEG moiety in lipegfilgrastim decreases the plasma clearance and extends the drug's terminal elimination half-life, allowing for less frequent dosing 1.
Target Actions Organism AGranulocyte colony-stimulating factor receptor agonistHumans - Absorption
In studies of healthy volunteers receiving a single subcutaneous injection of 6 mg of lipegfilgrastim, the peak plasma concentration of lipegfilgrastim was reached after a median of 30 to 36 hours 5. Based on its molecular weight, lipegfilgrastim is believed to be primarily absorbed via the lymphatic system then drained into the vascular system 7. Peak concentration and area under the curve, indicating full bioavailability, was lower in injection site of the thigh compared to subcutaneous injection in the abdomen and in the upper arm, with differences among the injection sites being the greatest in males compared to female subjects 5.
- Volume of distribution
Lipegfilgrastim has a weight-dependent volume of distribution of 70 mL/kg, indicating minimal distribution beyond the lymphatic or vascular system 7.
- Protein binding
Not Available
- Metabolism
Lipegfilgrastim is metabolised via intra- or extracellular degradation by proteolytic enzymes 5. Following binding to the G-CSF receptors, it is proposed to be internalized by neutrophils via a non-linear process, and then undergoes degradation within the cell by endogenous proteolytic enzymes. Alternatively, the linear pathway is likely due to extracellular protein degradation by neutrophil elastase and other plasma proteases 5.
- Route of elimination
Lipegfilgrastim undergoes two distinct clearance pathways: linear pathway composed of degradation by proteolytic enzymes and non-linear pathway involving neutrophil-mediated clearance 7. The elimination pathway by neutrophil-mediated clearance is saturated at higher doses 3. Lipegfilgrastim and its degraded fragments may undergo renal clearance 5.
- Half-life
The average terminal half-life ranged from approximately 32 to 62 hours after a single subcutaneous injection of 6 mg lipegfilgrastim in healthy individuals 5.
- Clearance
In a phase 1, multinational, open-label, single-arm study of paediatric patients with Ewing family of tumors or rhabdomyosarcoma treated with myelosuppressive chemotherapy, the mean apparent clearance (CL/F) was approximately 71 mL/h, 120 mL/h, and 116 mL/h for age groups of 2-6 years, 6-12 years, and 12-18 years, respectively 3.
- Adverse Effects
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In safety pharmacological studies in rats and dogs, lipegfilgrastim was well tolerated at a single subcutaneous dose of 10 mg/kg. In the renal excretion study in rats, an intravenous dose of 250 μg/kg was well tolerated 6. While mutagenicity and genotoxicity studies have not been conducted with lipegfilgrastim, G-CSF has been reported to stimulate tumour growth and intratumoural vessel density in animal tumour models 6.
- Pathways
- Not Available
- Pharmacogenomic Effects/ADRs
- Not Available
Interactions
- Drug Interactions
- This information should not be interpreted without the help of a healthcare provider. If you believe you are experiencing an interaction, contact a healthcare provider immediately. The absence of an interaction does not necessarily mean no interactions exist.
Drug Interaction Integrate drug-drug
interactions in your softwareAldesleukin Aldesleukin may increase the myelosuppressive activities of Lipegfilgrastim. Alemtuzumab Alemtuzumab may increase the myelosuppressive activities of Lipegfilgrastim. Altretamine Altretamine may increase the myelosuppressive activities of Lipegfilgrastim. Amsacrine Amsacrine may increase the myelosuppressive activities of Lipegfilgrastim. Antihemophilic factor (recombinant), PEGylated The therapeutic efficacy of Lipegfilgrastim can be decreased when used in combination with Antihemophilic factor (recombinant), PEGylated. - Food Interactions
- No interactions found.
Products
Drug product information from 10+ global regionsOur datasets provide approved product information including:dosage, form, labeller, route of administration, and marketing period.Access drug product information from over 10 global regions.- Brand Name Prescription Products
Name Dosage Strength Route Labeller Marketing Start Marketing End Region Image Lonquex Injection, solution 6 mg/0.6ml Subcutaneous Teva B.V. 2023-03-15 Not applicable EU 
Lonquex Injection, solution 6 mg Subcutaneous Teva B.V. 2016-09-08 Not applicable EU Lonquex Injection, solution 6 mg/0.6ml Subcutaneous Teva B.V. 2022-08-02 Not applicable EU Lonquex Injection, solution 6 mg Subcutaneous Teva B.V. 2016-09-08 Not applicable EU Lonquex Injection, solution 6 mg Subcutaneous Teva B.V. 2022-05-04 Not applicable EU
Categories
- ATC Codes
- L03AA14 — Lipegfilgrastim
- Drug Categories
- Adjuvants, Immunologic
- Alcohols
- Amino Acids, Peptides, and Proteins
- Antineoplastic and Immunomodulating Agents
- Biological Factors
- Carbohydrates
- Colony-Stimulating Factors
- Cytokines
- Ethylene Glycols
- Glycoconjugates
- Glycols
- Glycoproteins
- Granulocyte Colony-Stimulating Factors
- Hematopoietic Cell Growth Factors
- Intercellular Signaling Peptides and Proteins
- Macromolecular Substances
- Pegylated agents
- Peptides
- Polymers
- Proteins
- Chemical TaxonomyProvided by Classyfire
- Description
- Not Available
- Kingdom
- Organic Compounds
- Super Class
- Organic Acids
- Class
- Carboxylic Acids and Derivatives
- Sub Class
- Amino Acids, Peptides, and Analogues
- Direct Parent
- Peptides
- Alternative Parents
- Not Available
- Substituents
- Not Available
- Molecular Framework
- Not Available
- External Descriptors
- Not Available
- Affected organisms
- Not Available
Chemical Identifiers
- UNII
- 4AWF0N6QV3
- CAS number
- 1117844-87-7
References
- General References
- Buchner A, Lammerich A, Abdolzade-Bavil A, Muller U, Bias P: Lipegfilgrastim: pharmacodynamics and pharmacokinetics for body-weight-adjusted and 6 mg fixed doses in two randomized studies in healthy volunteers. Curr Med Res Opin. 2014 Dec;30(12):2523-33. doi: 10.1185/03007995.2014.962131. Epub 2014 Sep 25. [Article]
- Guariglia R, Martorelli MC, Lerose R, Telesca D, Milella MR, Musto P: Lipegfilgrastim in the management of chemotherapy-induced neutropenia of cancer patients. Biologics. 2016 Jan 22;10:1-8. doi: 10.2147/BTT.S58597. eCollection 2016. [Article]
- Belogurova MB, Kizyma ZP, Garami M, Csoka M, Lamson MJ, Buchner A, Bias P, Lammerich A: A pharmacokinetic study of lipegfilgrastim in children with Ewing family of tumors or rhabdomyosarcoma. Cancer Chemother Pharmacol. 2017 Jan;79(1):155-164. doi: 10.1007/s00280-016-3216-2. Epub 2016 Dec 16. [Article]
- 25. (2012). In Rang and Dale's Pharmacology (7th ed., pp. 315). Edinburgh: Elsevier/Churchill Livingstone. [ISBN:978-0-7020-3471-8]
- European Medicines Agency (EMA) Summary of Product Characteristics: Lonquex (lipegfilgrastim) [Link]
- Australian Public Assessment Report for Lipefilgrastim (rbe) [Link]
- Therapeutic Goods Administration (TGA) product Information: Lonquex [Link]
- External Links
- 1440046
- Wikipedia
- Lipegfilgrastim
- MSDS
- Download (20.2 KB)
Clinical Trials
- Clinical Trials
Clinical Trial & Rare Diseases Add-on Data Package
Explore 4,000+ rare diseases, orphan drugs & condition pairs, clinical trial why stopped data, & more. Preview package Phase Status Purpose Conditions Count Start Date Why Stopped 100+ additional columns Unlock 175K+ rows when you subscribe.View sample data3 Completed Treatment Aggressive B Cell Non-Hodgkin Lymphomas at High Risk for R-CHOP-21-induced Neutropenia 1 somestatus stop reason just information to hide 1 Completed Other Pharmacodynamics / Pharmacokinetics 1 somestatus stop reason just information to hide 1 Completed Supportive Care Ewing Family of Tumors, Rhabdomyosarcoma 1 somestatus stop reason just information to hide 1, 2 Unknown Status Treatment Lymphoma / Multiple Myeloma (MM) 1 somestatus stop reason just information to hide Not Available Completed Not Available Breast Cancer 1 somestatus stop reason just information to hide
Pharmacoeconomics
- Manufacturers
- Not Available
- Packagers
- Not Available
- Dosage Forms
Form Route Strength Solution Subcutaneous 6.000 mg Injection, solution Intramuscular; Subcutaneous 6 MG Injection, solution Parenteral; Subcutaneous 6 mg/0.6ml Injection, solution Parenteral; Subcutaneous 6 MG Injection, solution Subcutaneous 6 mg Injection, solution Subcutaneous 6 mg/0.6ml Injection, solution Subcutaneous 6.00 mg/0.6ml Injection, solution 10 mg/ml - Prices
- Not Available
- Patents
- Not Available
Properties
- State
- Liquid
- Experimental Properties
- Not Available
Targets
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Yes
- Actions
- Agonist
- General Function
- Receptor for granulocyte colony-stimulating factor (CSF3), essential for granulocytic maturation. Plays a crucial role in the proliferation, differentiation and survival of cells along the neutrophilic lineage. In addition it may function in some adhesion or recognition events at the cell surface
- Specific Function
- Cytokine binding
- Gene Name
- CSF3R
- Uniprot ID
- Q99062
- Uniprot Name
- Granulocyte colony-stimulating factor receptor
- Molecular Weight
- 92155.615 Da
Drug created at June 23, 2017 20:37 / Updated at May 27, 2021 02:58