Detailed description page of ThPDB2

This page displays user query in tabular form.

Th1571 details

Primary information
ID	15188
Therapeutic ID	Th1571
Protein Name	Lipegfilgrastim
Sequence	>Th1571_Lipegfilgrastim MTPLGPASSLPQSFLLKCLEQVRKIQGDGAALQEKLCATYKLCHPEELVLLGHSLGIPWAPLSSCPSQALQLAGCLSQLHSGLFLYQGLLQALEGISPELGPTLDTLQLDVADFATTIWQQMEELGMAPALQPTQGAMPAFASAFQRRAGGVLVASHLQSFLEVSYRVLRHLAQP
Molecular Weight	39000
Chemical Formula	C866H1372N226O258S9*(C2H4O)n
Isoelectric Point	NA
Hydrophobicity	NA
Melting point	NA
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 [L2441].
Description	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 [A32665]. It is used as an alternate to [DB00019] 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 [A32665]. 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 [A32665]. Lipegfilgrastim is a covalent conjugate of [DB00099] with a single methoxy polyethylene glycol (PEG) molecule via a carbohydrate linker consisting of glycine, N-acetylneuraminic acid and N-acetylgalactosamine [L2441]. The average molecular mass of lipegfilgrastim comprises 18,798 Da for [DB00099], 203 Da for GalNAc, 338 Da for glycylsialic acid and approximately 20,000 Da for PEG [L2449]. 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 [A32665].
Indication/Disease	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) [L2441].
Pharmacodynamics	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 [L2441]. Following a single subcutaneous dose administration of 100 µg/kg, lipegfilgrastim resulted in a significant increase in neutrophilic granulocyte and large unstained cell counts [L2449]. G-CSF also increases the antibacterial activities of neutrophils including the phagocytosis [L2441]. Due to structural similarity between lipegfilgrastim and pegfilgrastim, G-CSF receptor binding was equivalent between two molecules [A32665]. However, lipegfilgrastim showed greater time-dependent resistance to neutrophil elastase degradation and greater retention of activity than pegfilgrastim [A32665].
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 [T28]. Subsequently, G-SCF stimulates the release of matured neutrophils from the bone marrow storage pools into the peripheral blood to enhance their function [L2441, T28]. 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 [L2441]. This stimulatory effect of lipegfilgrastim may extend to other single lineage and multilineage progenitors and pluripotent haematopoietic stem cells [L2441]. 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 [A32664].
Toxicity	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 [L2449]. 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 [L2449].
Metabolism	Lipegfilgrastim is metabolised via intra- or extracellular degradation by proteolytic enzymes [L2441]. 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 [L2441].
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 [L2441]. Based on its molecular weight, lipegfilgrastim is believed to be primarily absorbed via the lymphatic system then drained into the vascular system [L2455]. 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 [L2441].
	Lipegfilgrastim has a weight-dependent volume of distribution of 70 mL/kg, indicating minimal distribution beyond the lymphatic or vascular system [L2455].
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 [A32674].
Categories	Adjuvants, Immunologic
Patents Number	NA
Date of Issue	NA
Date of Expiry	NA
Drug Interaction	NA
Target	Granulocyte colony-stimulating factor receptor
Brand Name	Lonquex
Company	Teva B.V.
Brand Description	Teva B.V.
Prescribed For	Subcutaneous
Chemical Name	6 mg
Formulation	NA
Physical Appearance	The most common side effects with Lonquex (which may affect more than 1 in 10 patients) are nausea as well as bone and muscle pain.
Route of Administration	Lonquex is a medicine that contains the active substance lipegfilgrastim. It is used to reduce the duration of neutropenia (low levels of neutrophils, a type of white blood cell) and the occurrence of febrile neutropenia (neutropenia with fever) in adult cancer patients receiving cytotoxic chemotherapy.
Recommended Dosage	used to reduce the duration of neutropenia (low levels of neutrophils, a type of white blood cell) and the occurrence of febrile neutropenia (neutropenia with fever) in adult cancer patients receiving cytotoxic chemotherapy.
Contraindication	2-[[5-acetamido-6-(1-amino-1-carboxypropan-2-yl)oxy-3,4-dihydroxyoxan-2-yl]methoxy]-4-hydroxy-5-[[2-(2-methoxyethoxycarbonylamino)acetyl]amino]-6-(1,2,3-trihydroxypropyl)oxane-2-carboxylic acid
Side Effects	NA
Useful Link 1	Link
Useful Link 2	Link
Remarks	NA

Primary information
ID	15189
Therapeutic ID	Th1571
Protein Name	Lipegfilgrastim
Sequence	>Th1571_Lipegfilgrastim MTPLGPASSLPQSFLLKCLEQVRKIQGDGAALQEKLCATYKLCHPEELVLLGHSLGIPWAPLSSCPSQALQLAGCLSQLHSGLFLYQGLLQALEGISPELGPTLDTLQLDVADFATTIWQQMEELGMAPALQPTQGAMPAFASAFQRRAGGVLVASHLQSFLEVSYRVLRHLAQP
Molecular Weight	39000
Chemical Formula	C866H1372N226O258S9*(C2H4O)n
Isoelectric Point	NA
Hydrophobicity	NA
Melting point	NA
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 [L2441].
Description	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 [A32665]. It is used as an alternate to [DB00019] 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 [A32665]. 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 [A32665]. Lipegfilgrastim is a covalent conjugate of [DB00099] with a single methoxy polyethylene glycol (PEG) molecule via a carbohydrate linker consisting of glycine, N-acetylneuraminic acid and N-acetylgalactosamine [L2441]. The average molecular mass of lipegfilgrastim comprises 18,798 Da for [DB00099], 203 Da for GalNAc, 338 Da for glycylsialic acid and approximately 20,000 Da for PEG [L2449]. 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 [A32665].
Indication/Disease	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) [L2441].
Pharmacodynamics	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 [L2441]. Following a single subcutaneous dose administration of 100 µg/kg, lipegfilgrastim resulted in a significant increase in neutrophilic granulocyte and large unstained cell counts [L2449]. G-CSF also increases the antibacterial activities of neutrophils including the phagocytosis [L2441]. Due to structural similarity between lipegfilgrastim and pegfilgrastim, G-CSF receptor binding was equivalent between two molecules [A32665]. However, lipegfilgrastim showed greater time-dependent resistance to neutrophil elastase degradation and greater retention of activity than pegfilgrastim [A32665].
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 [T28]. Subsequently, G-SCF stimulates the release of matured neutrophils from the bone marrow storage pools into the peripheral blood to enhance their function [L2441, T28]. 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 [L2441]. This stimulatory effect of lipegfilgrastim may extend to other single lineage and multilineage progenitors and pluripotent haematopoietic stem cells [L2441]. 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 [A32664].
Toxicity	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 [L2449]. 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 [L2449].
Metabolism	Lipegfilgrastim is metabolised via intra- or extracellular degradation by proteolytic enzymes [L2441]. 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 [L2441].
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 [L2441]. Based on its molecular weight, lipegfilgrastim is believed to be primarily absorbed via the lymphatic system then drained into the vascular system [L2455]. 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 [L2441].
	Lipegfilgrastim has a weight-dependent volume of distribution of 70 mL/kg, indicating minimal distribution beyond the lymphatic or vascular system [L2455].
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 [A32674].
Categories	Alcohols
Patents Number	NA
Date of Issue	NA
Date of Expiry	NA
Drug Interaction	NA
Target	Granulocyte colony-stimulating factor receptor
Brand Name	NA
Company	NA
Brand Description	NA
Prescribed For	NA
Chemical Name	NA
Formulation	NA
Physical Appearance	NA
Route of Administration	NA
Recommended Dosage	NA
Contraindication	2-[[5-acetamido-6-(1-amino-1-carboxypropan-2-yl)oxy-3,4-dihydroxyoxan-2-yl]methoxy]-4-hydroxy-5-[[2-(2-methoxyethoxycarbonylamino)acetyl]amino]-6-(1,2,3-trihydroxypropyl)oxane-2-carboxylic acid
Side Effects	NA
Useful Link 1	Link
Useful Link 2	NA
Remarks	NA

Primary information
ID	15190
Therapeutic ID	Th1571
Protein Name	Lipegfilgrastim
Sequence	>Th1571_Lipegfilgrastim MTPLGPASSLPQSFLLKCLEQVRKIQGDGAALQEKLCATYKLCHPEELVLLGHSLGIPWAPLSSCPSQALQLAGCLSQLHSGLFLYQGLLQALEGISPELGPTLDTLQLDVADFATTIWQQMEELGMAPALQPTQGAMPAFASAFQRRAGGVLVASHLQSFLEVSYRVLRHLAQP
Molecular Weight	39000
Chemical Formula	C866H1372N226O258S9*(C2H4O)n
Isoelectric Point	NA
Hydrophobicity	NA
Melting point	NA
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 [L2441].
Description	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 [A32665]. It is used as an alternate to [DB00019] 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 [A32665]. 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 [A32665]. Lipegfilgrastim is a covalent conjugate of [DB00099] with a single methoxy polyethylene glycol (PEG) molecule via a carbohydrate linker consisting of glycine, N-acetylneuraminic acid and N-acetylgalactosamine [L2441]. The average molecular mass of lipegfilgrastim comprises 18,798 Da for [DB00099], 203 Da for GalNAc, 338 Da for glycylsialic acid and approximately 20,000 Da for PEG [L2449]. 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 [A32665].
Indication/Disease	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) [L2441].
Pharmacodynamics	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 [L2441]. Following a single subcutaneous dose administration of 100 µg/kg, lipegfilgrastim resulted in a significant increase in neutrophilic granulocyte and large unstained cell counts [L2449]. G-CSF also increases the antibacterial activities of neutrophils including the phagocytosis [L2441]. Due to structural similarity between lipegfilgrastim and pegfilgrastim, G-CSF receptor binding was equivalent between two molecules [A32665]. However, lipegfilgrastim showed greater time-dependent resistance to neutrophil elastase degradation and greater retention of activity than pegfilgrastim [A32665].
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 [T28]. Subsequently, G-SCF stimulates the release of matured neutrophils from the bone marrow storage pools into the peripheral blood to enhance their function [L2441, T28]. 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 [L2441]. This stimulatory effect of lipegfilgrastim may extend to other single lineage and multilineage progenitors and pluripotent haematopoietic stem cells [L2441]. 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 [A32664].
Toxicity	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 [L2449]. 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 [L2449].
Metabolism	Lipegfilgrastim is metabolised via intra- or extracellular degradation by proteolytic enzymes [L2441]. 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 [L2441].
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 [L2441]. Based on its molecular weight, lipegfilgrastim is believed to be primarily absorbed via the lymphatic system then drained into the vascular system [L2455]. 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 [L2441].
	Lipegfilgrastim has a weight-dependent volume of distribution of 70 mL/kg, indicating minimal distribution beyond the lymphatic or vascular system [L2455].
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 [A32674].
Categories	Amino Acids, Peptides, and Proteins
Patents Number	NA
Date of Issue	NA
Date of Expiry	NA
Drug Interaction	NA
Target	Granulocyte colony-stimulating factor receptor
Brand Name	NA
Company	NA
Brand Description	NA
Prescribed For	NA
Chemical Name	NA
Formulation	NA
Physical Appearance	NA
Route of Administration	NA
Recommended Dosage	NA
Contraindication	2-[[5-acetamido-6-(1-amino-1-carboxypropan-2-yl)oxy-3,4-dihydroxyoxan-2-yl]methoxy]-4-hydroxy-5-[[2-(2-methoxyethoxycarbonylamino)acetyl]amino]-6-(1,2,3-trihydroxypropyl)oxane-2-carboxylic acid
Side Effects	NA
Useful Link 1	Link
Useful Link 2	NA
Remarks	NA

Primary information
ID	15191
Therapeutic ID	Th1571
Protein Name	Lipegfilgrastim
Sequence	>Th1571_Lipegfilgrastim MTPLGPASSLPQSFLLKCLEQVRKIQGDGAALQEKLCATYKLCHPEELVLLGHSLGIPWAPLSSCPSQALQLAGCLSQLHSGLFLYQGLLQALEGISPELGPTLDTLQLDVADFATTIWQQMEELGMAPALQPTQGAMPAFASAFQRRAGGVLVASHLQSFLEVSYRVLRHLAQP
Molecular Weight	39000
Chemical Formula	C866H1372N226O258S9*(C2H4O)n
Isoelectric Point	NA
Hydrophobicity	NA
Melting point	NA
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 [L2441].
Description	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 [A32665]. It is used as an alternate to [DB00019] 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 [A32665]. 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 [A32665]. Lipegfilgrastim is a covalent conjugate of [DB00099] with a single methoxy polyethylene glycol (PEG) molecule via a carbohydrate linker consisting of glycine, N-acetylneuraminic acid and N-acetylgalactosamine [L2441]. The average molecular mass of lipegfilgrastim comprises 18,798 Da for [DB00099], 203 Da for GalNAc, 338 Da for glycylsialic acid and approximately 20,000 Da for PEG [L2449]. 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 [A32665].
Indication/Disease	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) [L2441].
Pharmacodynamics	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 [L2441]. Following a single subcutaneous dose administration of 100 µg/kg, lipegfilgrastim resulted in a significant increase in neutrophilic granulocyte and large unstained cell counts [L2449]. G-CSF also increases the antibacterial activities of neutrophils including the phagocytosis [L2441]. Due to structural similarity between lipegfilgrastim and pegfilgrastim, G-CSF receptor binding was equivalent between two molecules [A32665]. However, lipegfilgrastim showed greater time-dependent resistance to neutrophil elastase degradation and greater retention of activity than pegfilgrastim [A32665].
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 [T28]. Subsequently, G-SCF stimulates the release of matured neutrophils from the bone marrow storage pools into the peripheral blood to enhance their function [L2441, T28]. 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 [L2441]. This stimulatory effect of lipegfilgrastim may extend to other single lineage and multilineage progenitors and pluripotent haematopoietic stem cells [L2441]. 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 [A32664].
Toxicity	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 [L2449]. 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 [L2449].
Metabolism	Lipegfilgrastim is metabolised via intra- or extracellular degradation by proteolytic enzymes [L2441]. 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 [L2441].
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 [L2441]. Based on its molecular weight, lipegfilgrastim is believed to be primarily absorbed via the lymphatic system then drained into the vascular system [L2455]. 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 [L2441].
	Lipegfilgrastim has a weight-dependent volume of distribution of 70 mL/kg, indicating minimal distribution beyond the lymphatic or vascular system [L2455].
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 [A32674].
Categories	Antineoplastic and Immunomodulating Agents
Patents Number	NA
Date of Issue	NA
Date of Expiry	NA
Drug Interaction	NA
Target	Granulocyte colony-stimulating factor receptor
Brand Name	NA
Company	NA
Brand Description	NA
Prescribed For	NA
Chemical Name	NA
Formulation	NA
Physical Appearance	NA
Route of Administration	NA
Recommended Dosage	NA
Contraindication	2-[[5-acetamido-6-(1-amino-1-carboxypropan-2-yl)oxy-3,4-dihydroxyoxan-2-yl]methoxy]-4-hydroxy-5-[[2-(2-methoxyethoxycarbonylamino)acetyl]amino]-6-(1,2,3-trihydroxypropyl)oxane-2-carboxylic acid
Side Effects	NA
Useful Link 1	Link
Useful Link 2	NA
Remarks	NA

Primary information
ID	15192
Therapeutic ID	Th1571
Protein Name	Lipegfilgrastim
Sequence	>Th1571_Lipegfilgrastim MTPLGPASSLPQSFLLKCLEQVRKIQGDGAALQEKLCATYKLCHPEELVLLGHSLGIPWAPLSSCPSQALQLAGCLSQLHSGLFLYQGLLQALEGISPELGPTLDTLQLDVADFATTIWQQMEELGMAPALQPTQGAMPAFASAFQRRAGGVLVASHLQSFLEVSYRVLRHLAQP
Molecular Weight	39000
Chemical Formula	C866H1372N226O258S9*(C2H4O)n
Isoelectric Point	NA
Hydrophobicity	NA
Melting point	NA
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 [L2441].
Description	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 [A32665]. It is used as an alternate to [DB00019] 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 [A32665]. 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 [A32665]. Lipegfilgrastim is a covalent conjugate of [DB00099] with a single methoxy polyethylene glycol (PEG) molecule via a carbohydrate linker consisting of glycine, N-acetylneuraminic acid and N-acetylgalactosamine [L2441]. The average molecular mass of lipegfilgrastim comprises 18,798 Da for [DB00099], 203 Da for GalNAc, 338 Da for glycylsialic acid and approximately 20,000 Da for PEG [L2449]. 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 [A32665].
Indication/Disease	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) [L2441].
Pharmacodynamics	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 [L2441]. Following a single subcutaneous dose administration of 100 µg/kg, lipegfilgrastim resulted in a significant increase in neutrophilic granulocyte and large unstained cell counts [L2449]. G-CSF also increases the antibacterial activities of neutrophils including the phagocytosis [L2441]. Due to structural similarity between lipegfilgrastim and pegfilgrastim, G-CSF receptor binding was equivalent between two molecules [A32665]. However, lipegfilgrastim showed greater time-dependent resistance to neutrophil elastase degradation and greater retention of activity than pegfilgrastim [A32665].
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 [T28]. Subsequently, G-SCF stimulates the release of matured neutrophils from the bone marrow storage pools into the peripheral blood to enhance their function [L2441, T28]. 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 [L2441]. This stimulatory effect of lipegfilgrastim may extend to other single lineage and multilineage progenitors and pluripotent haematopoietic stem cells [L2441]. 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 [A32664].
Toxicity	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 [L2449]. 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 [L2449].
Metabolism	Lipegfilgrastim is metabolised via intra- or extracellular degradation by proteolytic enzymes [L2441]. 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 [L2441].
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 [L2441]. Based on its molecular weight, lipegfilgrastim is believed to be primarily absorbed via the lymphatic system then drained into the vascular system [L2455]. 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 [L2441].
	Lipegfilgrastim has a weight-dependent volume of distribution of 70 mL/kg, indicating minimal distribution beyond the lymphatic or vascular system [L2455].
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 [A32674].
Categories	Biological Factors
Patents Number	NA
Date of Issue	NA
Date of Expiry	NA
Drug Interaction	NA
Target	Granulocyte colony-stimulating factor receptor
Brand Name	NA
Company	NA
Brand Description	NA
Prescribed For	NA
Chemical Name	NA
Formulation	NA
Physical Appearance	NA
Route of Administration	NA
Recommended Dosage	NA
Contraindication	2-[[5-acetamido-6-(1-amino-1-carboxypropan-2-yl)oxy-3,4-dihydroxyoxan-2-yl]methoxy]-4-hydroxy-5-[[2-(2-methoxyethoxycarbonylamino)acetyl]amino]-6-(1,2,3-trihydroxypropyl)oxane-2-carboxylic acid
Side Effects	NA
Useful Link 1	Link
Useful Link 2	NA
Remarks	NA

Primary information
ID	15193
Therapeutic ID	Th1571
Protein Name	Lipegfilgrastim
Sequence	>Th1571_Lipegfilgrastim MTPLGPASSLPQSFLLKCLEQVRKIQGDGAALQEKLCATYKLCHPEELVLLGHSLGIPWAPLSSCPSQALQLAGCLSQLHSGLFLYQGLLQALEGISPELGPTLDTLQLDVADFATTIWQQMEELGMAPALQPTQGAMPAFASAFQRRAGGVLVASHLQSFLEVSYRVLRHLAQP
Molecular Weight	39000
Chemical Formula	C866H1372N226O258S9*(C2H4O)n
Isoelectric Point	NA
Hydrophobicity	NA
Melting point	NA
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 [L2441].
Description	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 [A32665]. It is used as an alternate to [DB00019] 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 [A32665]. 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 [A32665]. Lipegfilgrastim is a covalent conjugate of [DB00099] with a single methoxy polyethylene glycol (PEG) molecule via a carbohydrate linker consisting of glycine, N-acetylneuraminic acid and N-acetylgalactosamine [L2441]. The average molecular mass of lipegfilgrastim comprises 18,798 Da for [DB00099], 203 Da for GalNAc, 338 Da for glycylsialic acid and approximately 20,000 Da for PEG [L2449]. 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 [A32665].
Indication/Disease	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) [L2441].
Pharmacodynamics	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 [L2441]. Following a single subcutaneous dose administration of 100 µg/kg, lipegfilgrastim resulted in a significant increase in neutrophilic granulocyte and large unstained cell counts [L2449]. G-CSF also increases the antibacterial activities of neutrophils including the phagocytosis [L2441]. Due to structural similarity between lipegfilgrastim and pegfilgrastim, G-CSF receptor binding was equivalent between two molecules [A32665]. However, lipegfilgrastim showed greater time-dependent resistance to neutrophil elastase degradation and greater retention of activity than pegfilgrastim [A32665].
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 [T28]. Subsequently, G-SCF stimulates the release of matured neutrophils from the bone marrow storage pools into the peripheral blood to enhance their function [L2441, T28]. 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 [L2441]. This stimulatory effect of lipegfilgrastim may extend to other single lineage and multilineage progenitors and pluripotent haematopoietic stem cells [L2441]. 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 [A32664].
Toxicity	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 [L2449]. 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 [L2449].
Metabolism	Lipegfilgrastim is metabolised via intra- or extracellular degradation by proteolytic enzymes [L2441]. 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 [L2441].
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 [L2441]. Based on its molecular weight, lipegfilgrastim is believed to be primarily absorbed via the lymphatic system then drained into the vascular system [L2455]. 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 [L2441].
	Lipegfilgrastim has a weight-dependent volume of distribution of 70 mL/kg, indicating minimal distribution beyond the lymphatic or vascular system [L2455].
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 [A32674].
Categories	Carbohydrates
Patents Number	NA
Date of Issue	NA
Date of Expiry	NA
Drug Interaction	NA
Target	Granulocyte colony-stimulating factor receptor
Brand Name	NA
Company	NA
Brand Description	NA
Prescribed For	NA
Chemical Name	NA
Formulation	NA
Physical Appearance	NA
Route of Administration	NA
Recommended Dosage	NA
Contraindication	2-[[5-acetamido-6-(1-amino-1-carboxypropan-2-yl)oxy-3,4-dihydroxyoxan-2-yl]methoxy]-4-hydroxy-5-[[2-(2-methoxyethoxycarbonylamino)acetyl]amino]-6-(1,2,3-trihydroxypropyl)oxane-2-carboxylic acid
Side Effects	NA
Useful Link 1	Link
Useful Link 2	NA
Remarks	NA

Primary information
ID	15194
Therapeutic ID	Th1571
Protein Name	Lipegfilgrastim
Sequence	>Th1571_Lipegfilgrastim MTPLGPASSLPQSFLLKCLEQVRKIQGDGAALQEKLCATYKLCHPEELVLLGHSLGIPWAPLSSCPSQALQLAGCLSQLHSGLFLYQGLLQALEGISPELGPTLDTLQLDVADFATTIWQQMEELGMAPALQPTQGAMPAFASAFQRRAGGVLVASHLQSFLEVSYRVLRHLAQP
Molecular Weight	39000
Chemical Formula	C866H1372N226O258S9*(C2H4O)n
Isoelectric Point	NA
Hydrophobicity	NA
Melting point	NA
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 [L2441].
Description	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 [A32665]. It is used as an alternate to [DB00019] 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 [A32665]. 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 [A32665]. Lipegfilgrastim is a covalent conjugate of [DB00099] with a single methoxy polyethylene glycol (PEG) molecule via a carbohydrate linker consisting of glycine, N-acetylneuraminic acid and N-acetylgalactosamine [L2441]. The average molecular mass of lipegfilgrastim comprises 18,798 Da for [DB00099], 203 Da for GalNAc, 338 Da for glycylsialic acid and approximately 20,000 Da for PEG [L2449]. 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 [A32665].
Indication/Disease	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) [L2441].
Pharmacodynamics	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 [L2441]. Following a single subcutaneous dose administration of 100 µg/kg, lipegfilgrastim resulted in a significant increase in neutrophilic granulocyte and large unstained cell counts [L2449]. G-CSF also increases the antibacterial activities of neutrophils including the phagocytosis [L2441]. Due to structural similarity between lipegfilgrastim and pegfilgrastim, G-CSF receptor binding was equivalent between two molecules [A32665]. However, lipegfilgrastim showed greater time-dependent resistance to neutrophil elastase degradation and greater retention of activity than pegfilgrastim [A32665].
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 [T28]. Subsequently, G-SCF stimulates the release of matured neutrophils from the bone marrow storage pools into the peripheral blood to enhance their function [L2441, T28]. 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 [L2441]. This stimulatory effect of lipegfilgrastim may extend to other single lineage and multilineage progenitors and pluripotent haematopoietic stem cells [L2441]. 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 [A32664].
Toxicity	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 [L2449]. 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 [L2449].
Metabolism	Lipegfilgrastim is metabolised via intra- or extracellular degradation by proteolytic enzymes [L2441]. 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 [L2441].
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 [L2441]. Based on its molecular weight, lipegfilgrastim is believed to be primarily absorbed via the lymphatic system then drained into the vascular system [L2455]. 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 [L2441].
	Lipegfilgrastim has a weight-dependent volume of distribution of 70 mL/kg, indicating minimal distribution beyond the lymphatic or vascular system [L2455].
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 [A32674].
Categories	Colony-Stimulating Factors
Patents Number	NA
Date of Issue	NA
Date of Expiry	NA
Drug Interaction	NA
Target	Granulocyte colony-stimulating factor receptor
Brand Name	NA
Company	NA
Brand Description	NA
Prescribed For	NA
Chemical Name	NA
Formulation	NA
Physical Appearance	NA
Route of Administration	NA
Recommended Dosage	NA
Contraindication	2-[[5-acetamido-6-(1-amino-1-carboxypropan-2-yl)oxy-3,4-dihydroxyoxan-2-yl]methoxy]-4-hydroxy-5-[[2-(2-methoxyethoxycarbonylamino)acetyl]amino]-6-(1,2,3-trihydroxypropyl)oxane-2-carboxylic acid
Side Effects	NA
Useful Link 1	Link
Useful Link 2	NA
Remarks	NA

Primary information
ID	15195
Therapeutic ID	Th1571
Protein Name	Lipegfilgrastim
Sequence	>Th1571_Lipegfilgrastim MTPLGPASSLPQSFLLKCLEQVRKIQGDGAALQEKLCATYKLCHPEELVLLGHSLGIPWAPLSSCPSQALQLAGCLSQLHSGLFLYQGLLQALEGISPELGPTLDTLQLDVADFATTIWQQMEELGMAPALQPTQGAMPAFASAFQRRAGGVLVASHLQSFLEVSYRVLRHLAQP
Molecular Weight	39000
Chemical Formula	C866H1372N226O258S9*(C2H4O)n
Isoelectric Point	NA
Hydrophobicity	NA
Melting point	NA
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 [L2441].
Description	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 [A32665]. It is used as an alternate to [DB00019] 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 [A32665]. 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 [A32665]. Lipegfilgrastim is a covalent conjugate of [DB00099] with a single methoxy polyethylene glycol (PEG) molecule via a carbohydrate linker consisting of glycine, N-acetylneuraminic acid and N-acetylgalactosamine [L2441]. The average molecular mass of lipegfilgrastim comprises 18,798 Da for [DB00099], 203 Da for GalNAc, 338 Da for glycylsialic acid and approximately 20,000 Da for PEG [L2449]. 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 [A32665].
Indication/Disease	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) [L2441].
Pharmacodynamics	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 [L2441]. Following a single subcutaneous dose administration of 100 µg/kg, lipegfilgrastim resulted in a significant increase in neutrophilic granulocyte and large unstained cell counts [L2449]. G-CSF also increases the antibacterial activities of neutrophils including the phagocytosis [L2441]. Due to structural similarity between lipegfilgrastim and pegfilgrastim, G-CSF receptor binding was equivalent between two molecules [A32665]. However, lipegfilgrastim showed greater time-dependent resistance to neutrophil elastase degradation and greater retention of activity than pegfilgrastim [A32665].
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 [T28]. Subsequently, G-SCF stimulates the release of matured neutrophils from the bone marrow storage pools into the peripheral blood to enhance their function [L2441, T28]. 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 [L2441]. This stimulatory effect of lipegfilgrastim may extend to other single lineage and multilineage progenitors and pluripotent haematopoietic stem cells [L2441]. 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 [A32664].
Toxicity	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 [L2449]. 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 [L2449].
Metabolism	Lipegfilgrastim is metabolised via intra- or extracellular degradation by proteolytic enzymes [L2441]. 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 [L2441].
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 [L2441]. Based on its molecular weight, lipegfilgrastim is believed to be primarily absorbed via the lymphatic system then drained into the vascular system [L2455]. 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 [L2441].
	Lipegfilgrastim has a weight-dependent volume of distribution of 70 mL/kg, indicating minimal distribution beyond the lymphatic or vascular system [L2455].
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 [A32674].
Categories	Compounds used in a research, industrial, or household setting
Patents Number	NA
Date of Issue	NA
Date of Expiry	NA
Drug Interaction	NA
Target	Granulocyte colony-stimulating factor receptor
Brand Name	NA
Company	NA
Brand Description	NA
Prescribed For	NA
Chemical Name	NA
Formulation	NA
Physical Appearance	NA
Route of Administration	NA
Recommended Dosage	NA
Contraindication	2-[[5-acetamido-6-(1-amino-1-carboxypropan-2-yl)oxy-3,4-dihydroxyoxan-2-yl]methoxy]-4-hydroxy-5-[[2-(2-methoxyethoxycarbonylamino)acetyl]amino]-6-(1,2,3-trihydroxypropyl)oxane-2-carboxylic acid
Side Effects	NA
Useful Link 1	Link
Useful Link 2	NA
Remarks	NA

Primary information
ID	15196
Therapeutic ID	Th1571
Protein Name	Lipegfilgrastim
Sequence	>Th1571_Lipegfilgrastim MTPLGPASSLPQSFLLKCLEQVRKIQGDGAALQEKLCATYKLCHPEELVLLGHSLGIPWAPLSSCPSQALQLAGCLSQLHSGLFLYQGLLQALEGISPELGPTLDTLQLDVADFATTIWQQMEELGMAPALQPTQGAMPAFASAFQRRAGGVLVASHLQSFLEVSYRVLRHLAQP
Molecular Weight	39000
Chemical Formula	C866H1372N226O258S9*(C2H4O)n
Isoelectric Point	NA
Hydrophobicity	NA
Melting point	NA
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 [L2441].
Description	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 [A32665]. It is used as an alternate to [DB00019] 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 [A32665]. 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 [A32665]. Lipegfilgrastim is a covalent conjugate of [DB00099] with a single methoxy polyethylene glycol (PEG) molecule via a carbohydrate linker consisting of glycine, N-acetylneuraminic acid and N-acetylgalactosamine [L2441]. The average molecular mass of lipegfilgrastim comprises 18,798 Da for [DB00099], 203 Da for GalNAc, 338 Da for glycylsialic acid and approximately 20,000 Da for PEG [L2449]. 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 [A32665].
Indication/Disease	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) [L2441].
Pharmacodynamics	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 [L2441]. Following a single subcutaneous dose administration of 100 µg/kg, lipegfilgrastim resulted in a significant increase in neutrophilic granulocyte and large unstained cell counts [L2449]. G-CSF also increases the antibacterial activities of neutrophils including the phagocytosis [L2441]. Due to structural similarity between lipegfilgrastim and pegfilgrastim, G-CSF receptor binding was equivalent between two molecules [A32665]. However, lipegfilgrastim showed greater time-dependent resistance to neutrophil elastase degradation and greater retention of activity than pegfilgrastim [A32665].
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 [T28]. Subsequently, G-SCF stimulates the release of matured neutrophils from the bone marrow storage pools into the peripheral blood to enhance their function [L2441, T28]. 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 [L2441]. This stimulatory effect of lipegfilgrastim may extend to other single lineage and multilineage progenitors and pluripotent haematopoietic stem cells [L2441]. 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 [A32664].
Toxicity	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 [L2449]. 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 [L2449].
Metabolism	Lipegfilgrastim is metabolised via intra- or extracellular degradation by proteolytic enzymes [L2441]. 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 [L2441].
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 [L2441]. Based on its molecular weight, lipegfilgrastim is believed to be primarily absorbed via the lymphatic system then drained into the vascular system [L2455]. 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 [L2441].
	Lipegfilgrastim has a weight-dependent volume of distribution of 70 mL/kg, indicating minimal distribution beyond the lymphatic or vascular system [L2455].
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 [A32674].
Categories	Cytokines
Patents Number	NA
Date of Issue	NA
Date of Expiry	NA
Drug Interaction	NA
Target	Granulocyte colony-stimulating factor receptor
Brand Name	NA
Company	NA
Brand Description	NA
Prescribed For	NA
Chemical Name	NA
Formulation	NA
Physical Appearance	NA
Route of Administration	NA
Recommended Dosage	NA
Contraindication	2-[[5-acetamido-6-(1-amino-1-carboxypropan-2-yl)oxy-3,4-dihydroxyoxan-2-yl]methoxy]-4-hydroxy-5-[[2-(2-methoxyethoxycarbonylamino)acetyl]amino]-6-(1,2,3-trihydroxypropyl)oxane-2-carboxylic acid
Side Effects	NA
Useful Link 1	Link
Useful Link 2	NA
Remarks	NA

Primary information
ID	15197
Therapeutic ID	Th1571
Protein Name	Lipegfilgrastim
Sequence	>Th1571_Lipegfilgrastim MTPLGPASSLPQSFLLKCLEQVRKIQGDGAALQEKLCATYKLCHPEELVLLGHSLGIPWAPLSSCPSQALQLAGCLSQLHSGLFLYQGLLQALEGISPELGPTLDTLQLDVADFATTIWQQMEELGMAPALQPTQGAMPAFASAFQRRAGGVLVASHLQSFLEVSYRVLRHLAQP
Molecular Weight	39000
Chemical Formula	C866H1372N226O258S9*(C2H4O)n
Isoelectric Point	NA
Hydrophobicity	NA
Melting point	NA
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 [L2441].
Description	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 [A32665]. It is used as an alternate to [DB00019] 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 [A32665]. 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 [A32665]. Lipegfilgrastim is a covalent conjugate of [DB00099] with a single methoxy polyethylene glycol (PEG) molecule via a carbohydrate linker consisting of glycine, N-acetylneuraminic acid and N-acetylgalactosamine [L2441]. The average molecular mass of lipegfilgrastim comprises 18,798 Da for [DB00099], 203 Da for GalNAc, 338 Da for glycylsialic acid and approximately 20,000 Da for PEG [L2449]. 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 [A32665].
Indication/Disease	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) [L2441].
Pharmacodynamics	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 [L2441]. Following a single subcutaneous dose administration of 100 µg/kg, lipegfilgrastim resulted in a significant increase in neutrophilic granulocyte and large unstained cell counts [L2449]. G-CSF also increases the antibacterial activities of neutrophils including the phagocytosis [L2441]. Due to structural similarity between lipegfilgrastim and pegfilgrastim, G-CSF receptor binding was equivalent between two molecules [A32665]. However, lipegfilgrastim showed greater time-dependent resistance to neutrophil elastase degradation and greater retention of activity than pegfilgrastim [A32665].
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 [T28]. Subsequently, G-SCF stimulates the release of matured neutrophils from the bone marrow storage pools into the peripheral blood to enhance their function [L2441, T28]. 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 [L2441]. This stimulatory effect of lipegfilgrastim may extend to other single lineage and multilineage progenitors and pluripotent haematopoietic stem cells [L2441]. 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 [A32664].
Toxicity	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 [L2449]. 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 [L2449].
Metabolism	Lipegfilgrastim is metabolised via intra- or extracellular degradation by proteolytic enzymes [L2441]. 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 [L2441].
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 [L2441]. Based on its molecular weight, lipegfilgrastim is believed to be primarily absorbed via the lymphatic system then drained into the vascular system [L2455]. 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 [L2441].
	Lipegfilgrastim has a weight-dependent volume of distribution of 70 mL/kg, indicating minimal distribution beyond the lymphatic or vascular system [L2455].
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 [A32674].
Categories	Ethylene Glycols
Patents Number	NA
Date of Issue	NA
Date of Expiry	NA
Drug Interaction	NA
Target	Granulocyte colony-stimulating factor receptor
Brand Name	NA
Company	NA
Brand Description	NA
Prescribed For	NA
Chemical Name	NA
Formulation	NA
Physical Appearance	NA
Route of Administration	NA
Recommended Dosage	NA
Contraindication	2-[[5-acetamido-6-(1-amino-1-carboxypropan-2-yl)oxy-3,4-dihydroxyoxan-2-yl]methoxy]-4-hydroxy-5-[[2-(2-methoxyethoxycarbonylamino)acetyl]amino]-6-(1,2,3-trihydroxypropyl)oxane-2-carboxylic acid
Side Effects	NA
Useful Link 1	Link
Useful Link 2	NA
Remarks	NA

Primary information
ID	15198
Therapeutic ID	Th1571
Protein Name	Lipegfilgrastim
Sequence	>Th1571_Lipegfilgrastim MTPLGPASSLPQSFLLKCLEQVRKIQGDGAALQEKLCATYKLCHPEELVLLGHSLGIPWAPLSSCPSQALQLAGCLSQLHSGLFLYQGLLQALEGISPELGPTLDTLQLDVADFATTIWQQMEELGMAPALQPTQGAMPAFASAFQRRAGGVLVASHLQSFLEVSYRVLRHLAQP
Molecular Weight	39000
Chemical Formula	C866H1372N226O258S9*(C2H4O)n
Isoelectric Point	NA
Hydrophobicity	NA
Melting point	NA
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 [L2441].
Description	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 [A32665]. It is used as an alternate to [DB00019] 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 [A32665]. 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 [A32665]. Lipegfilgrastim is a covalent conjugate of [DB00099] with a single methoxy polyethylene glycol (PEG) molecule via a carbohydrate linker consisting of glycine, N-acetylneuraminic acid and N-acetylgalactosamine [L2441]. The average molecular mass of lipegfilgrastim comprises 18,798 Da for [DB00099], 203 Da for GalNAc, 338 Da for glycylsialic acid and approximately 20,000 Da for PEG [L2449]. 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 [A32665].
Indication/Disease	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) [L2441].
Pharmacodynamics	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 [L2441]. Following a single subcutaneous dose administration of 100 µg/kg, lipegfilgrastim resulted in a significant increase in neutrophilic granulocyte and large unstained cell counts [L2449]. G-CSF also increases the antibacterial activities of neutrophils including the phagocytosis [L2441]. Due to structural similarity between lipegfilgrastim and pegfilgrastim, G-CSF receptor binding was equivalent between two molecules [A32665]. However, lipegfilgrastim showed greater time-dependent resistance to neutrophil elastase degradation and greater retention of activity than pegfilgrastim [A32665].
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 [T28]. Subsequently, G-SCF stimulates the release of matured neutrophils from the bone marrow storage pools into the peripheral blood to enhance their function [L2441, T28]. 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 [L2441]. This stimulatory effect of lipegfilgrastim may extend to other single lineage and multilineage progenitors and pluripotent haematopoietic stem cells [L2441]. 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 [A32664].
Toxicity	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 [L2449]. 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 [L2449].
Metabolism	Lipegfilgrastim is metabolised via intra- or extracellular degradation by proteolytic enzymes [L2441]. 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 [L2441].
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 [L2441]. Based on its molecular weight, lipegfilgrastim is believed to be primarily absorbed via the lymphatic system then drained into the vascular system [L2455]. 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 [L2441].
	Lipegfilgrastim has a weight-dependent volume of distribution of 70 mL/kg, indicating minimal distribution beyond the lymphatic or vascular system [L2455].
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 [A32674].
Categories	Glycoconjugates
Patents Number	NA
Date of Issue	NA
Date of Expiry	NA
Drug Interaction	NA
Target	Granulocyte colony-stimulating factor receptor
Brand Name	NA
Company	NA
Brand Description	NA
Prescribed For	NA
Chemical Name	NA
Formulation	NA
Physical Appearance	NA
Route of Administration	NA
Recommended Dosage	NA
Contraindication	2-[[5-acetamido-6-(1-amino-1-carboxypropan-2-yl)oxy-3,4-dihydroxyoxan-2-yl]methoxy]-4-hydroxy-5-[[2-(2-methoxyethoxycarbonylamino)acetyl]amino]-6-(1,2,3-trihydroxypropyl)oxane-2-carboxylic acid
Side Effects	NA
Useful Link 1	Link
Useful Link 2	NA
Remarks	NA

Primary information
ID	15199
Therapeutic ID	Th1571
Protein Name	Lipegfilgrastim
Sequence	>Th1571_Lipegfilgrastim MTPLGPASSLPQSFLLKCLEQVRKIQGDGAALQEKLCATYKLCHPEELVLLGHSLGIPWAPLSSCPSQALQLAGCLSQLHSGLFLYQGLLQALEGISPELGPTLDTLQLDVADFATTIWQQMEELGMAPALQPTQGAMPAFASAFQRRAGGVLVASHLQSFLEVSYRVLRHLAQP
Molecular Weight	39000
Chemical Formula	C866H1372N226O258S9*(C2H4O)n
Isoelectric Point	NA
Hydrophobicity	NA
Melting point	NA
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 [L2441].
Description	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 [A32665]. It is used as an alternate to [DB00019] 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 [A32665]. 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 [A32665]. Lipegfilgrastim is a covalent conjugate of [DB00099] with a single methoxy polyethylene glycol (PEG) molecule via a carbohydrate linker consisting of glycine, N-acetylneuraminic acid and N-acetylgalactosamine [L2441]. The average molecular mass of lipegfilgrastim comprises 18,798 Da for [DB00099], 203 Da for GalNAc, 338 Da for glycylsialic acid and approximately 20,000 Da for PEG [L2449]. 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 [A32665].
Indication/Disease	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) [L2441].
Pharmacodynamics	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 [L2441]. Following a single subcutaneous dose administration of 100 µg/kg, lipegfilgrastim resulted in a significant increase in neutrophilic granulocyte and large unstained cell counts [L2449]. G-CSF also increases the antibacterial activities of neutrophils including the phagocytosis [L2441]. Due to structural similarity between lipegfilgrastim and pegfilgrastim, G-CSF receptor binding was equivalent between two molecules [A32665]. However, lipegfilgrastim showed greater time-dependent resistance to neutrophil elastase degradation and greater retention of activity than pegfilgrastim [A32665].
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 [T28]. Subsequently, G-SCF stimulates the release of matured neutrophils from the bone marrow storage pools into the peripheral blood to enhance their function [L2441, T28]. 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 [L2441]. This stimulatory effect of lipegfilgrastim may extend to other single lineage and multilineage progenitors and pluripotent haematopoietic stem cells [L2441]. 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 [A32664].
Toxicity	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 [L2449]. 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 [L2449].
Metabolism	Lipegfilgrastim is metabolised via intra- or extracellular degradation by proteolytic enzymes [L2441]. 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 [L2441].
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 [L2441]. Based on its molecular weight, lipegfilgrastim is believed to be primarily absorbed via the lymphatic system then drained into the vascular system [L2455]. 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 [L2441].
	Lipegfilgrastim has a weight-dependent volume of distribution of 70 mL/kg, indicating minimal distribution beyond the lymphatic or vascular system [L2455].
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 [A32674].
Categories	Glycols
Patents Number	NA
Date of Issue	NA
Date of Expiry	NA
Drug Interaction	NA
Target	Granulocyte colony-stimulating factor receptor
Brand Name	NA
Company	NA
Brand Description	NA
Prescribed For	NA
Chemical Name	NA
Formulation	NA
Physical Appearance	NA
Route of Administration	NA
Recommended Dosage	NA
Contraindication	2-[[5-acetamido-6-(1-amino-1-carboxypropan-2-yl)oxy-3,4-dihydroxyoxan-2-yl]methoxy]-4-hydroxy-5-[[2-(2-methoxyethoxycarbonylamino)acetyl]amino]-6-(1,2,3-trihydroxypropyl)oxane-2-carboxylic acid
Side Effects	NA
Useful Link 1	Link
Useful Link 2	NA
Remarks	NA

Primary information
ID	15200
Therapeutic ID	Th1571
Protein Name	Lipegfilgrastim
Sequence	>Th1571_Lipegfilgrastim MTPLGPASSLPQSFLLKCLEQVRKIQGDGAALQEKLCATYKLCHPEELVLLGHSLGIPWAPLSSCPSQALQLAGCLSQLHSGLFLYQGLLQALEGISPELGPTLDTLQLDVADFATTIWQQMEELGMAPALQPTQGAMPAFASAFQRRAGGVLVASHLQSFLEVSYRVLRHLAQP
Molecular Weight	39000
Chemical Formula	C866H1372N226O258S9*(C2H4O)n
Isoelectric Point	NA
Hydrophobicity	NA
Melting point	NA
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 [L2441].
Description	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 [A32665]. It is used as an alternate to [DB00019] 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 [A32665]. 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 [A32665]. Lipegfilgrastim is a covalent conjugate of [DB00099] with a single methoxy polyethylene glycol (PEG) molecule via a carbohydrate linker consisting of glycine, N-acetylneuraminic acid and N-acetylgalactosamine [L2441]. The average molecular mass of lipegfilgrastim comprises 18,798 Da for [DB00099], 203 Da for GalNAc, 338 Da for glycylsialic acid and approximately 20,000 Da for PEG [L2449]. 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 [A32665].
Indication/Disease	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) [L2441].
Pharmacodynamics	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 [L2441]. Following a single subcutaneous dose administration of 100 µg/kg, lipegfilgrastim resulted in a significant increase in neutrophilic granulocyte and large unstained cell counts [L2449]. G-CSF also increases the antibacterial activities of neutrophils including the phagocytosis [L2441]. Due to structural similarity between lipegfilgrastim and pegfilgrastim, G-CSF receptor binding was equivalent between two molecules [A32665]. However, lipegfilgrastim showed greater time-dependent resistance to neutrophil elastase degradation and greater retention of activity than pegfilgrastim [A32665].
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 [T28]. Subsequently, G-SCF stimulates the release of matured neutrophils from the bone marrow storage pools into the peripheral blood to enhance their function [L2441, T28]. 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 [L2441]. This stimulatory effect of lipegfilgrastim may extend to other single lineage and multilineage progenitors and pluripotent haematopoietic stem cells [L2441]. 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 [A32664].
Toxicity	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 [L2449]. 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 [L2449].
Metabolism	Lipegfilgrastim is metabolised via intra- or extracellular degradation by proteolytic enzymes [L2441]. 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 [L2441].
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 [L2441]. Based on its molecular weight, lipegfilgrastim is believed to be primarily absorbed via the lymphatic system then drained into the vascular system [L2455]. 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 [L2441].
	Lipegfilgrastim has a weight-dependent volume of distribution of 70 mL/kg, indicating minimal distribution beyond the lymphatic or vascular system [L2455].
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 [A32674].
Categories	Glycoproteins
Patents Number	NA
Date of Issue	NA
Date of Expiry	NA
Drug Interaction	NA
Target	Granulocyte colony-stimulating factor receptor
Brand Name	NA
Company	NA
Brand Description	NA
Prescribed For	NA
Chemical Name	NA
Formulation	NA
Physical Appearance	NA
Route of Administration	NA
Recommended Dosage	NA
Contraindication	2-[[5-acetamido-6-(1-amino-1-carboxypropan-2-yl)oxy-3,4-dihydroxyoxan-2-yl]methoxy]-4-hydroxy-5-[[2-(2-methoxyethoxycarbonylamino)acetyl]amino]-6-(1,2,3-trihydroxypropyl)oxane-2-carboxylic acid
Side Effects	NA
Useful Link 1	Link
Useful Link 2	NA
Remarks	NA

Primary information
ID	15201
Therapeutic ID	Th1571
Protein Name	Lipegfilgrastim
Sequence	>Th1571_Lipegfilgrastim MTPLGPASSLPQSFLLKCLEQVRKIQGDGAALQEKLCATYKLCHPEELVLLGHSLGIPWAPLSSCPSQALQLAGCLSQLHSGLFLYQGLLQALEGISPELGPTLDTLQLDVADFATTIWQQMEELGMAPALQPTQGAMPAFASAFQRRAGGVLVASHLQSFLEVSYRVLRHLAQP
Molecular Weight	39000
Chemical Formula	C866H1372N226O258S9*(C2H4O)n
Isoelectric Point	NA
Hydrophobicity	NA
Melting point	NA
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 [L2441].
Description	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 [A32665]. It is used as an alternate to [DB00019] 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 [A32665]. 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 [A32665]. Lipegfilgrastim is a covalent conjugate of [DB00099] with a single methoxy polyethylene glycol (PEG) molecule via a carbohydrate linker consisting of glycine, N-acetylneuraminic acid and N-acetylgalactosamine [L2441]. The average molecular mass of lipegfilgrastim comprises 18,798 Da for [DB00099], 203 Da for GalNAc, 338 Da for glycylsialic acid and approximately 20,000 Da for PEG [L2449]. 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 [A32665].
Indication/Disease	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) [L2441].
Pharmacodynamics	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 [L2441]. Following a single subcutaneous dose administration of 100 µg/kg, lipegfilgrastim resulted in a significant increase in neutrophilic granulocyte and large unstained cell counts [L2449]. G-CSF also increases the antibacterial activities of neutrophils including the phagocytosis [L2441]. Due to structural similarity between lipegfilgrastim and pegfilgrastim, G-CSF receptor binding was equivalent between two molecules [A32665]. However, lipegfilgrastim showed greater time-dependent resistance to neutrophil elastase degradation and greater retention of activity than pegfilgrastim [A32665].
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 [T28]. Subsequently, G-SCF stimulates the release of matured neutrophils from the bone marrow storage pools into the peripheral blood to enhance their function [L2441, T28]. 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 [L2441]. This stimulatory effect of lipegfilgrastim may extend to other single lineage and multilineage progenitors and pluripotent haematopoietic stem cells [L2441]. 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 [A32664].
Toxicity	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 [L2449]. 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 [L2449].
Metabolism	Lipegfilgrastim is metabolised via intra- or extracellular degradation by proteolytic enzymes [L2441]. 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 [L2441].
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 [L2441]. Based on its molecular weight, lipegfilgrastim is believed to be primarily absorbed via the lymphatic system then drained into the vascular system [L2455]. 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 [L2441].
	Lipegfilgrastim has a weight-dependent volume of distribution of 70 mL/kg, indicating minimal distribution beyond the lymphatic or vascular system [L2455].
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 [A32674].
Categories	Granulocyte Colony-Stimulating Factors
Patents Number	NA
Date of Issue	NA
Date of Expiry	NA
Drug Interaction	NA
Target	Granulocyte colony-stimulating factor receptor
Brand Name	NA
Company	NA
Brand Description	NA
Prescribed For	NA
Chemical Name	NA
Formulation	NA
Physical Appearance	NA
Route of Administration	NA
Recommended Dosage	NA
Contraindication	2-[[5-acetamido-6-(1-amino-1-carboxypropan-2-yl)oxy-3,4-dihydroxyoxan-2-yl]methoxy]-4-hydroxy-5-[[2-(2-methoxyethoxycarbonylamino)acetyl]amino]-6-(1,2,3-trihydroxypropyl)oxane-2-carboxylic acid
Side Effects	NA
Useful Link 1	Link
Useful Link 2	NA
Remarks	NA

Primary information
ID	15202
Therapeutic ID	Th1571
Protein Name	Lipegfilgrastim
Sequence	>Th1571_Lipegfilgrastim MTPLGPASSLPQSFLLKCLEQVRKIQGDGAALQEKLCATYKLCHPEELVLLGHSLGIPWAPLSSCPSQALQLAGCLSQLHSGLFLYQGLLQALEGISPELGPTLDTLQLDVADFATTIWQQMEELGMAPALQPTQGAMPAFASAFQRRAGGVLVASHLQSFLEVSYRVLRHLAQP
Molecular Weight	39000
Chemical Formula	C866H1372N226O258S9*(C2H4O)n
Isoelectric Point	NA
Hydrophobicity	NA
Melting point	NA
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 [L2441].
Description	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 [A32665]. It is used as an alternate to [DB00019] 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 [A32665]. 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 [A32665]. Lipegfilgrastim is a covalent conjugate of [DB00099] with a single methoxy polyethylene glycol (PEG) molecule via a carbohydrate linker consisting of glycine, N-acetylneuraminic acid and N-acetylgalactosamine [L2441]. The average molecular mass of lipegfilgrastim comprises 18,798 Da for [DB00099], 203 Da for GalNAc, 338 Da for glycylsialic acid and approximately 20,000 Da for PEG [L2449]. 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 [A32665].
Indication/Disease	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) [L2441].
Pharmacodynamics	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 [L2441]. Following a single subcutaneous dose administration of 100 µg/kg, lipegfilgrastim resulted in a significant increase in neutrophilic granulocyte and large unstained cell counts [L2449]. G-CSF also increases the antibacterial activities of neutrophils including the phagocytosis [L2441]. Due to structural similarity between lipegfilgrastim and pegfilgrastim, G-CSF receptor binding was equivalent between two molecules [A32665]. However, lipegfilgrastim showed greater time-dependent resistance to neutrophil elastase degradation and greater retention of activity than pegfilgrastim [A32665].
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 [T28]. Subsequently, G-SCF stimulates the release of matured neutrophils from the bone marrow storage pools into the peripheral blood to enhance their function [L2441, T28]. 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 [L2441]. This stimulatory effect of lipegfilgrastim may extend to other single lineage and multilineage progenitors and pluripotent haematopoietic stem cells [L2441]. 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 [A32664].
Toxicity	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 [L2449]. 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 [L2449].
Metabolism	Lipegfilgrastim is metabolised via intra- or extracellular degradation by proteolytic enzymes [L2441]. 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 [L2441].
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 [L2441]. Based on its molecular weight, lipegfilgrastim is believed to be primarily absorbed via the lymphatic system then drained into the vascular system [L2455]. 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 [L2441].
	Lipegfilgrastim has a weight-dependent volume of distribution of 70 mL/kg, indicating minimal distribution beyond the lymphatic or vascular system [L2455].
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 [A32674].
Categories	Hematopoietic Cell Growth Factors
Patents Number	NA
Date of Issue	NA
Date of Expiry	NA
Drug Interaction	NA
Target	Granulocyte colony-stimulating factor receptor
Brand Name	NA
Company	NA
Brand Description	NA
Prescribed For	NA
Chemical Name	NA
Formulation	NA
Physical Appearance	NA
Route of Administration	NA
Recommended Dosage	NA
Contraindication	2-[[5-acetamido-6-(1-amino-1-carboxypropan-2-yl)oxy-3,4-dihydroxyoxan-2-yl]methoxy]-4-hydroxy-5-[[2-(2-methoxyethoxycarbonylamino)acetyl]amino]-6-(1,2,3-trihydroxypropyl)oxane-2-carboxylic acid
Side Effects	NA
Useful Link 1	Link
Useful Link 2	NA
Remarks	NA

Primary information
ID	15203
Therapeutic ID	Th1571
Protein Name	Lipegfilgrastim
Sequence	>Th1571_Lipegfilgrastim MTPLGPASSLPQSFLLKCLEQVRKIQGDGAALQEKLCATYKLCHPEELVLLGHSLGIPWAPLSSCPSQALQLAGCLSQLHSGLFLYQGLLQALEGISPELGPTLDTLQLDVADFATTIWQQMEELGMAPALQPTQGAMPAFASAFQRRAGGVLVASHLQSFLEVSYRVLRHLAQP
Molecular Weight	39000
Chemical Formula	C866H1372N226O258S9*(C2H4O)n
Isoelectric Point	NA
Hydrophobicity	NA
Melting point	NA
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 [L2441].
Description	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 [A32665]. It is used as an alternate to [DB00019] 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 [A32665]. 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 [A32665]. Lipegfilgrastim is a covalent conjugate of [DB00099] with a single methoxy polyethylene glycol (PEG) molecule via a carbohydrate linker consisting of glycine, N-acetylneuraminic acid and N-acetylgalactosamine [L2441]. The average molecular mass of lipegfilgrastim comprises 18,798 Da for [DB00099], 203 Da for GalNAc, 338 Da for glycylsialic acid and approximately 20,000 Da for PEG [L2449]. 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 [A32665].
Indication/Disease	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) [L2441].
Pharmacodynamics	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 [L2441]. Following a single subcutaneous dose administration of 100 µg/kg, lipegfilgrastim resulted in a significant increase in neutrophilic granulocyte and large unstained cell counts [L2449]. G-CSF also increases the antibacterial activities of neutrophils including the phagocytosis [L2441]. Due to structural similarity between lipegfilgrastim and pegfilgrastim, G-CSF receptor binding was equivalent between two molecules [A32665]. However, lipegfilgrastim showed greater time-dependent resistance to neutrophil elastase degradation and greater retention of activity than pegfilgrastim [A32665].
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 [T28]. Subsequently, G-SCF stimulates the release of matured neutrophils from the bone marrow storage pools into the peripheral blood to enhance their function [L2441, T28]. 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 [L2441]. This stimulatory effect of lipegfilgrastim may extend to other single lineage and multilineage progenitors and pluripotent haematopoietic stem cells [L2441]. 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 [A32664].
Toxicity	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 [L2449]. 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 [L2449].
Metabolism	Lipegfilgrastim is metabolised via intra- or extracellular degradation by proteolytic enzymes [L2441]. 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 [L2441].
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 [L2441]. Based on its molecular weight, lipegfilgrastim is believed to be primarily absorbed via the lymphatic system then drained into the vascular system [L2455]. 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 [L2441].
	Lipegfilgrastim has a weight-dependent volume of distribution of 70 mL/kg, indicating minimal distribution beyond the lymphatic or vascular system [L2455].
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 [A32674].
Categories	Intercellular Signaling Peptides and Proteins
Patents Number	NA
Date of Issue	NA
Date of Expiry	NA
Drug Interaction	NA
Target	Granulocyte colony-stimulating factor receptor
Brand Name	NA
Company	NA
Brand Description	NA
Prescribed For	NA
Chemical Name	NA
Formulation	NA
Physical Appearance	NA
Route of Administration	NA
Recommended Dosage	NA
Contraindication	2-[[5-acetamido-6-(1-amino-1-carboxypropan-2-yl)oxy-3,4-dihydroxyoxan-2-yl]methoxy]-4-hydroxy-5-[[2-(2-methoxyethoxycarbonylamino)acetyl]amino]-6-(1,2,3-trihydroxypropyl)oxane-2-carboxylic acid
Side Effects	NA
Useful Link 1	Link
Useful Link 2	NA
Remarks	NA

Primary information
ID	15204
Therapeutic ID	Th1571
Protein Name	Lipegfilgrastim
Sequence	>Th1571_Lipegfilgrastim MTPLGPASSLPQSFLLKCLEQVRKIQGDGAALQEKLCATYKLCHPEELVLLGHSLGIPWAPLSSCPSQALQLAGCLSQLHSGLFLYQGLLQALEGISPELGPTLDTLQLDVADFATTIWQQMEELGMAPALQPTQGAMPAFASAFQRRAGGVLVASHLQSFLEVSYRVLRHLAQP
Molecular Weight	39000
Chemical Formula	C866H1372N226O258S9*(C2H4O)n
Isoelectric Point	NA
Hydrophobicity	NA
Melting point	NA
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 [L2441].
Description	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 [A32665]. It is used as an alternate to [DB00019] 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 [A32665]. 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 [A32665]. Lipegfilgrastim is a covalent conjugate of [DB00099] with a single methoxy polyethylene glycol (PEG) molecule via a carbohydrate linker consisting of glycine, N-acetylneuraminic acid and N-acetylgalactosamine [L2441]. The average molecular mass of lipegfilgrastim comprises 18,798 Da for [DB00099], 203 Da for GalNAc, 338 Da for glycylsialic acid and approximately 20,000 Da for PEG [L2449]. 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 [A32665].
Indication/Disease	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) [L2441].
Pharmacodynamics	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 [L2441]. Following a single subcutaneous dose administration of 100 µg/kg, lipegfilgrastim resulted in a significant increase in neutrophilic granulocyte and large unstained cell counts [L2449]. G-CSF also increases the antibacterial activities of neutrophils including the phagocytosis [L2441]. Due to structural similarity between lipegfilgrastim and pegfilgrastim, G-CSF receptor binding was equivalent between two molecules [A32665]. However, lipegfilgrastim showed greater time-dependent resistance to neutrophil elastase degradation and greater retention of activity than pegfilgrastim [A32665].
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 [T28]. Subsequently, G-SCF stimulates the release of matured neutrophils from the bone marrow storage pools into the peripheral blood to enhance their function [L2441, T28]. 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 [L2441]. This stimulatory effect of lipegfilgrastim may extend to other single lineage and multilineage progenitors and pluripotent haematopoietic stem cells [L2441]. 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 [A32664].
Toxicity	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 [L2449]. 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 [L2449].
Metabolism	Lipegfilgrastim is metabolised via intra- or extracellular degradation by proteolytic enzymes [L2441]. 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 [L2441].
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 [L2441]. Based on its molecular weight, lipegfilgrastim is believed to be primarily absorbed via the lymphatic system then drained into the vascular system [L2455]. 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 [L2441].
	Lipegfilgrastim has a weight-dependent volume of distribution of 70 mL/kg, indicating minimal distribution beyond the lymphatic or vascular system [L2455].
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 [A32674].
Categories	Macromolecular Substances
Patents Number	NA
Date of Issue	NA
Date of Expiry	NA
Drug Interaction	NA
Target	Granulocyte colony-stimulating factor receptor
Brand Name	NA
Company	NA
Brand Description	NA
Prescribed For	NA
Chemical Name	NA
Formulation	NA
Physical Appearance	NA
Route of Administration	NA
Recommended Dosage	NA
Contraindication	2-[[5-acetamido-6-(1-amino-1-carboxypropan-2-yl)oxy-3,4-dihydroxyoxan-2-yl]methoxy]-4-hydroxy-5-[[2-(2-methoxyethoxycarbonylamino)acetyl]amino]-6-(1,2,3-trihydroxypropyl)oxane-2-carboxylic acid
Side Effects	NA
Useful Link 1	Link
Useful Link 2	NA
Remarks	NA

Primary information
ID	15205
Therapeutic ID	Th1571
Protein Name	Lipegfilgrastim
Sequence	>Th1571_Lipegfilgrastim MTPLGPASSLPQSFLLKCLEQVRKIQGDGAALQEKLCATYKLCHPEELVLLGHSLGIPWAPLSSCPSQALQLAGCLSQLHSGLFLYQGLLQALEGISPELGPTLDTLQLDVADFATTIWQQMEELGMAPALQPTQGAMPAFASAFQRRAGGVLVASHLQSFLEVSYRVLRHLAQP
Molecular Weight	39000
Chemical Formula	C866H1372N226O258S9*(C2H4O)n
Isoelectric Point	NA
Hydrophobicity	NA
Melting point	NA
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 [L2441].
Description	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 [A32665]. It is used as an alternate to [DB00019] 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 [A32665]. 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 [A32665]. Lipegfilgrastim is a covalent conjugate of [DB00099] with a single methoxy polyethylene glycol (PEG) molecule via a carbohydrate linker consisting of glycine, N-acetylneuraminic acid and N-acetylgalactosamine [L2441]. The average molecular mass of lipegfilgrastim comprises 18,798 Da for [DB00099], 203 Da for GalNAc, 338 Da for glycylsialic acid and approximately 20,000 Da for PEG [L2449]. 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 [A32665].
Indication/Disease	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) [L2441].
Pharmacodynamics	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 [L2441]. Following a single subcutaneous dose administration of 100 µg/kg, lipegfilgrastim resulted in a significant increase in neutrophilic granulocyte and large unstained cell counts [L2449]. G-CSF also increases the antibacterial activities of neutrophils including the phagocytosis [L2441]. Due to structural similarity between lipegfilgrastim and pegfilgrastim, G-CSF receptor binding was equivalent between two molecules [A32665]. However, lipegfilgrastim showed greater time-dependent resistance to neutrophil elastase degradation and greater retention of activity than pegfilgrastim [A32665].
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 [T28]. Subsequently, G-SCF stimulates the release of matured neutrophils from the bone marrow storage pools into the peripheral blood to enhance their function [L2441, T28]. 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 [L2441]. This stimulatory effect of lipegfilgrastim may extend to other single lineage and multilineage progenitors and pluripotent haematopoietic stem cells [L2441]. 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 [A32664].
Toxicity	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 [L2449]. 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 [L2449].
Metabolism	Lipegfilgrastim is metabolised via intra- or extracellular degradation by proteolytic enzymes [L2441]. 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 [L2441].
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 [L2441]. Based on its molecular weight, lipegfilgrastim is believed to be primarily absorbed via the lymphatic system then drained into the vascular system [L2455]. 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 [L2441].
	Lipegfilgrastim has a weight-dependent volume of distribution of 70 mL/kg, indicating minimal distribution beyond the lymphatic or vascular system [L2455].
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 [A32674].
Categories	Pegylated agents
Patents Number	NA
Date of Issue	NA
Date of Expiry	NA
Drug Interaction	NA
Target	Granulocyte colony-stimulating factor receptor
Brand Name	NA
Company	NA
Brand Description	NA
Prescribed For	NA
Chemical Name	NA
Formulation	NA
Physical Appearance	NA
Route of Administration	NA
Recommended Dosage	NA
Contraindication	2-[[5-acetamido-6-(1-amino-1-carboxypropan-2-yl)oxy-3,4-dihydroxyoxan-2-yl]methoxy]-4-hydroxy-5-[[2-(2-methoxyethoxycarbonylamino)acetyl]amino]-6-(1,2,3-trihydroxypropyl)oxane-2-carboxylic acid
Side Effects	NA
Useful Link 1	Link
Useful Link 2	NA
Remarks	NA

Primary information
ID	15206
Therapeutic ID	Th1571
Protein Name	Lipegfilgrastim
Sequence	>Th1571_Lipegfilgrastim MTPLGPASSLPQSFLLKCLEQVRKIQGDGAALQEKLCATYKLCHPEELVLLGHSLGIPWAPLSSCPSQALQLAGCLSQLHSGLFLYQGLLQALEGISPELGPTLDTLQLDVADFATTIWQQMEELGMAPALQPTQGAMPAFASAFQRRAGGVLVASHLQSFLEVSYRVLRHLAQP
Molecular Weight	39000
Chemical Formula	C866H1372N226O258S9*(C2H4O)n
Isoelectric Point	NA
Hydrophobicity	NA
Melting point	NA
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 [L2441].
Description	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 [A32665]. It is used as an alternate to [DB00019] 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 [A32665]. 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 [A32665]. Lipegfilgrastim is a covalent conjugate of [DB00099] with a single methoxy polyethylene glycol (PEG) molecule via a carbohydrate linker consisting of glycine, N-acetylneuraminic acid and N-acetylgalactosamine [L2441]. The average molecular mass of lipegfilgrastim comprises 18,798 Da for [DB00099], 203 Da for GalNAc, 338 Da for glycylsialic acid and approximately 20,000 Da for PEG [L2449]. 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 [A32665].
Indication/Disease	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) [L2441].
Pharmacodynamics	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 [L2441]. Following a single subcutaneous dose administration of 100 µg/kg, lipegfilgrastim resulted in a significant increase in neutrophilic granulocyte and large unstained cell counts [L2449]. G-CSF also increases the antibacterial activities of neutrophils including the phagocytosis [L2441]. Due to structural similarity between lipegfilgrastim and pegfilgrastim, G-CSF receptor binding was equivalent between two molecules [A32665]. However, lipegfilgrastim showed greater time-dependent resistance to neutrophil elastase degradation and greater retention of activity than pegfilgrastim [A32665].
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 [T28]. Subsequently, G-SCF stimulates the release of matured neutrophils from the bone marrow storage pools into the peripheral blood to enhance their function [L2441, T28]. 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 [L2441]. This stimulatory effect of lipegfilgrastim may extend to other single lineage and multilineage progenitors and pluripotent haematopoietic stem cells [L2441]. 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 [A32664].
Toxicity	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 [L2449]. 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 [L2449].
Metabolism	Lipegfilgrastim is metabolised via intra- or extracellular degradation by proteolytic enzymes [L2441]. 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 [L2441].
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 [L2441]. Based on its molecular weight, lipegfilgrastim is believed to be primarily absorbed via the lymphatic system then drained into the vascular system [L2455]. 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 [L2441].
	Lipegfilgrastim has a weight-dependent volume of distribution of 70 mL/kg, indicating minimal distribution beyond the lymphatic or vascular system [L2455].
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 [A32674].
Categories	Peptides
Patents Number	NA
Date of Issue	NA
Date of Expiry	NA
Drug Interaction	NA
Target	Granulocyte colony-stimulating factor receptor
Brand Name	NA
Company	NA
Brand Description	NA
Prescribed For	NA
Chemical Name	NA
Formulation	NA
Physical Appearance	NA
Route of Administration	NA
Recommended Dosage	NA
Contraindication	2-[[5-acetamido-6-(1-amino-1-carboxypropan-2-yl)oxy-3,4-dihydroxyoxan-2-yl]methoxy]-4-hydroxy-5-[[2-(2-methoxyethoxycarbonylamino)acetyl]amino]-6-(1,2,3-trihydroxypropyl)oxane-2-carboxylic acid
Side Effects	NA
Useful Link 1	Link
Useful Link 2	NA
Remarks	NA

Primary information
ID	15207
Therapeutic ID	Th1571
Protein Name	Lipegfilgrastim
Sequence	>Th1571_Lipegfilgrastim MTPLGPASSLPQSFLLKCLEQVRKIQGDGAALQEKLCATYKLCHPEELVLLGHSLGIPWAPLSSCPSQALQLAGCLSQLHSGLFLYQGLLQALEGISPELGPTLDTLQLDVADFATTIWQQMEELGMAPALQPTQGAMPAFASAFQRRAGGVLVASHLQSFLEVSYRVLRHLAQP
Molecular Weight	39000
Chemical Formula	C866H1372N226O258S9*(C2H4O)n
Isoelectric Point	NA
Hydrophobicity	NA
Melting point	NA
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 [L2441].
Description	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 [A32665]. It is used as an alternate to [DB00019] 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 [A32665]. 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 [A32665]. Lipegfilgrastim is a covalent conjugate of [DB00099] with a single methoxy polyethylene glycol (PEG) molecule via a carbohydrate linker consisting of glycine, N-acetylneuraminic acid and N-acetylgalactosamine [L2441]. The average molecular mass of lipegfilgrastim comprises 18,798 Da for [DB00099], 203 Da for GalNAc, 338 Da for glycylsialic acid and approximately 20,000 Da for PEG [L2449]. 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 [A32665].
Indication/Disease	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) [L2441].
Pharmacodynamics	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 [L2441]. Following a single subcutaneous dose administration of 100 µg/kg, lipegfilgrastim resulted in a significant increase in neutrophilic granulocyte and large unstained cell counts [L2449]. G-CSF also increases the antibacterial activities of neutrophils including the phagocytosis [L2441]. Due to structural similarity between lipegfilgrastim and pegfilgrastim, G-CSF receptor binding was equivalent between two molecules [A32665]. However, lipegfilgrastim showed greater time-dependent resistance to neutrophil elastase degradation and greater retention of activity than pegfilgrastim [A32665].
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 [T28]. Subsequently, G-SCF stimulates the release of matured neutrophils from the bone marrow storage pools into the peripheral blood to enhance their function [L2441, T28]. 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 [L2441]. This stimulatory effect of lipegfilgrastim may extend to other single lineage and multilineage progenitors and pluripotent haematopoietic stem cells [L2441]. 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 [A32664].
Toxicity	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 [L2449]. 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 [L2449].
Metabolism	Lipegfilgrastim is metabolised via intra- or extracellular degradation by proteolytic enzymes [L2441]. 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 [L2441].
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 [L2441]. Based on its molecular weight, lipegfilgrastim is believed to be primarily absorbed via the lymphatic system then drained into the vascular system [L2455]. 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 [L2441].
	Lipegfilgrastim has a weight-dependent volume of distribution of 70 mL/kg, indicating minimal distribution beyond the lymphatic or vascular system [L2455].
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 [A32674].
Categories	Polymers
Patents Number	NA
Date of Issue	NA
Date of Expiry	NA
Drug Interaction	NA
Target	Granulocyte colony-stimulating factor receptor
Brand Name	NA
Company	NA
Brand Description	NA
Prescribed For	NA
Chemical Name	NA
Formulation	NA
Physical Appearance	NA
Route of Administration	NA
Recommended Dosage	NA
Contraindication	2-[[5-acetamido-6-(1-amino-1-carboxypropan-2-yl)oxy-3,4-dihydroxyoxan-2-yl]methoxy]-4-hydroxy-5-[[2-(2-methoxyethoxycarbonylamino)acetyl]amino]-6-(1,2,3-trihydroxypropyl)oxane-2-carboxylic acid
Side Effects	NA
Useful Link 1	Link
Useful Link 2	NA
Remarks	NA

Primary information
ID	15208
Therapeutic ID	Th1571
Protein Name	Lipegfilgrastim
Sequence	>Th1571_Lipegfilgrastim MTPLGPASSLPQSFLLKCLEQVRKIQGDGAALQEKLCATYKLCHPEELVLLGHSLGIPWAPLSSCPSQALQLAGCLSQLHSGLFLYQGLLQALEGISPELGPTLDTLQLDVADFATTIWQQMEELGMAPALQPTQGAMPAFASAFQRRAGGVLVASHLQSFLEVSYRVLRHLAQP
Molecular Weight	39000
Chemical Formula	C866H1372N226O258S9*(C2H4O)n
Isoelectric Point	NA
Hydrophobicity	NA
Melting point	NA
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 [L2441].
Description	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 [A32665]. It is used as an alternate to [DB00019] 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 [A32665]. 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 [A32665]. Lipegfilgrastim is a covalent conjugate of [DB00099] with a single methoxy polyethylene glycol (PEG) molecule via a carbohydrate linker consisting of glycine, N-acetylneuraminic acid and N-acetylgalactosamine [L2441]. The average molecular mass of lipegfilgrastim comprises 18,798 Da for [DB00099], 203 Da for GalNAc, 338 Da for glycylsialic acid and approximately 20,000 Da for PEG [L2449]. 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 [A32665].
Indication/Disease	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) [L2441].
Pharmacodynamics	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 [L2441]. Following a single subcutaneous dose administration of 100 µg/kg, lipegfilgrastim resulted in a significant increase in neutrophilic granulocyte and large unstained cell counts [L2449]. G-CSF also increases the antibacterial activities of neutrophils including the phagocytosis [L2441]. Due to structural similarity between lipegfilgrastim and pegfilgrastim, G-CSF receptor binding was equivalent between two molecules [A32665]. However, lipegfilgrastim showed greater time-dependent resistance to neutrophil elastase degradation and greater retention of activity than pegfilgrastim [A32665].
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 [T28]. Subsequently, G-SCF stimulates the release of matured neutrophils from the bone marrow storage pools into the peripheral blood to enhance their function [L2441, T28]. 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 [L2441]. This stimulatory effect of lipegfilgrastim may extend to other single lineage and multilineage progenitors and pluripotent haematopoietic stem cells [L2441]. 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 [A32664].
Toxicity	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 [L2449]. 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 [L2449].
Metabolism	Lipegfilgrastim is metabolised via intra- or extracellular degradation by proteolytic enzymes [L2441]. 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 [L2441].
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 [L2441]. Based on its molecular weight, lipegfilgrastim is believed to be primarily absorbed via the lymphatic system then drained into the vascular system [L2455]. 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 [L2441].
	Lipegfilgrastim has a weight-dependent volume of distribution of 70 mL/kg, indicating minimal distribution beyond the lymphatic or vascular system [L2455].
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 [A32674].
Categories	Proteins
Patents Number	NA
Date of Issue	NA
Date of Expiry	NA
Drug Interaction	NA
Target	Granulocyte colony-stimulating factor receptor
Brand Name	NA
Company	NA
Brand Description	NA
Prescribed For	NA
Chemical Name	NA
Formulation	NA
Physical Appearance	NA
Route of Administration	NA
Recommended Dosage	NA
Contraindication	2-[[5-acetamido-6-(1-amino-1-carboxypropan-2-yl)oxy-3,4-dihydroxyoxan-2-yl]methoxy]-4-hydroxy-5-[[2-(2-methoxyethoxycarbonylamino)acetyl]amino]-6-(1,2,3-trihydroxypropyl)oxane-2-carboxylic acid
Side Effects	NA
Useful Link 1	Link
Useful Link 2	NA
Remarks	NA