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Role of lipegfilgrastim in the management of chemotherapy-induced neutropenia.

Hoggatt J, Tate TA, Pelus LM - Int J Nanomedicine (2015)

Bottom Line: However, while these therapies are effective against most cancers, the high proliferative rate of the cells of the hematopoietic system that produce billions of blood cells needed daily throughout life is extremely sensitive to these agents, resulting in loss of blood cell populations, which can be life threatening.Neutropenic patients often require hospitalization and incur substantial medical costs associated with anti-infective therapy.In this review, we will summarize the chemical characteristics, pharmacokinetics, safety and efficacy of lipegfilgrastim (Lonquex(®)), the first long-acting biosimilar filgrastim to receive regulatory approval and enter the marketplace.

View Article: PubMed Central - PubMed

Affiliation: Department of Stem Cell and Regenerative Biology, Harvard University, Cambridge, MA, USA.

ABSTRACT
Chemotherapy, irradiation, and other agents are widely used to target the process of cell division in neoplastic cells. However, while these therapies are effective against most cancers, the high proliferative rate of the cells of the hematopoietic system that produce billions of blood cells needed daily throughout life is extremely sensitive to these agents, resulting in loss of blood cell populations, which can be life threatening. Neutropenia is the most serious hematologic toxicity of chemotherapy, which can result in patient morbidity and mortality due to opportunistic infection and often is the limiting factor in dose escalation or duration of chemotherapeutic administration. Neutropenic patients often require hospitalization and incur substantial medical costs associated with anti-infective therapy. Treatment of iatrogenic and congenic neutropenia was changed in the early 1990s with the introduction of filgrastim (Neupogen(®)) and pegfilgrastim (Neulasta(®)). With the expiration of patent lives of both of these drugs, biosimilars have begun to emerge. In this review, we will summarize the chemical characteristics, pharmacokinetics, safety and efficacy of lipegfilgrastim (Lonquex(®)), the first long-acting biosimilar filgrastim to receive regulatory approval and enter the marketplace.

No MeSH data available.


Related in: MedlinePlus

Lipegfilgrastim is the result of a two-step enzymatic reaction.Notes: Addition of an O-glycan at the open threonine 134 site of filgrastim is achieved by enzymatic activity of a selective, truncated N-acetylgalactosaminyltransferase isoform 2 fused with maltose-binding protein at the threonine residue within the chosen site. A 20-kDa PEG-sialic acid derivative is then enzymatically transferred to the O-glycan with a sialyltransferase.Abbreviations: G-CSF, granulocyte colony–stimulating factor; PEG, polyethylene glycol.
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f1-ijn-10-2647: Lipegfilgrastim is the result of a two-step enzymatic reaction.Notes: Addition of an O-glycan at the open threonine 134 site of filgrastim is achieved by enzymatic activity of a selective, truncated N-acetylgalactosaminyltransferase isoform 2 fused with maltose-binding protein at the threonine residue within the chosen site. A 20-kDa PEG-sialic acid derivative is then enzymatically transferred to the O-glycan with a sialyltransferase.Abbreviations: G-CSF, granulocyte colony–stimulating factor; PEG, polyethylene glycol.

Mentions: Lipegfilgrastim is a long-acting, site-specific glycol-pegylated r-metHu G-CSF produced by conjugation of a single 20-kDa PEG to the natural O-glycosylation site of G-CSF (threonine 134), using a novel glycoPEGylation technology (Figure 1). Because the recombinant G-CSF is produced in Escherichia coli, the glycosylation site is empty. Addition of the O-glycan was achieved by enzymatic activity of a truncated N-acetylgalactosaminyltransferase isoform 2 fused with maltose-binding protein at the threonine residue site. A 20-kDa PEG-sialic acid derivative was enzymatically transferred to the O-glycan with a sialyltransferase. In contrast, pegfilgrastim (Neulasta®) is a recombinant methionyl human G-CSF with a methoxy-polyethylene glycol propionaldehyde 20-kDa PEG covalently conjugated to its N-terminus.28,29 The novel pegylation process used in lipegfilgrastim results in different pharmacokinetic and pharmacodynamic profiles than pegfilgrastim, as discussed later.


Role of lipegfilgrastim in the management of chemotherapy-induced neutropenia.

Hoggatt J, Tate TA, Pelus LM - Int J Nanomedicine (2015)

Lipegfilgrastim is the result of a two-step enzymatic reaction.Notes: Addition of an O-glycan at the open threonine 134 site of filgrastim is achieved by enzymatic activity of a selective, truncated N-acetylgalactosaminyltransferase isoform 2 fused with maltose-binding protein at the threonine residue within the chosen site. A 20-kDa PEG-sialic acid derivative is then enzymatically transferred to the O-glycan with a sialyltransferase.Abbreviations: G-CSF, granulocyte colony–stimulating factor; PEG, polyethylene glycol.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4388090&req=5

f1-ijn-10-2647: Lipegfilgrastim is the result of a two-step enzymatic reaction.Notes: Addition of an O-glycan at the open threonine 134 site of filgrastim is achieved by enzymatic activity of a selective, truncated N-acetylgalactosaminyltransferase isoform 2 fused with maltose-binding protein at the threonine residue within the chosen site. A 20-kDa PEG-sialic acid derivative is then enzymatically transferred to the O-glycan with a sialyltransferase.Abbreviations: G-CSF, granulocyte colony–stimulating factor; PEG, polyethylene glycol.
Mentions: Lipegfilgrastim is a long-acting, site-specific glycol-pegylated r-metHu G-CSF produced by conjugation of a single 20-kDa PEG to the natural O-glycosylation site of G-CSF (threonine 134), using a novel glycoPEGylation technology (Figure 1). Because the recombinant G-CSF is produced in Escherichia coli, the glycosylation site is empty. Addition of the O-glycan was achieved by enzymatic activity of a truncated N-acetylgalactosaminyltransferase isoform 2 fused with maltose-binding protein at the threonine residue site. A 20-kDa PEG-sialic acid derivative was enzymatically transferred to the O-glycan with a sialyltransferase. In contrast, pegfilgrastim (Neulasta®) is a recombinant methionyl human G-CSF with a methoxy-polyethylene glycol propionaldehyde 20-kDa PEG covalently conjugated to its N-terminus.28,29 The novel pegylation process used in lipegfilgrastim results in different pharmacokinetic and pharmacodynamic profiles than pegfilgrastim, as discussed later.

Bottom Line: However, while these therapies are effective against most cancers, the high proliferative rate of the cells of the hematopoietic system that produce billions of blood cells needed daily throughout life is extremely sensitive to these agents, resulting in loss of blood cell populations, which can be life threatening.Neutropenic patients often require hospitalization and incur substantial medical costs associated with anti-infective therapy.In this review, we will summarize the chemical characteristics, pharmacokinetics, safety and efficacy of lipegfilgrastim (Lonquex(®)), the first long-acting biosimilar filgrastim to receive regulatory approval and enter the marketplace.

View Article: PubMed Central - PubMed

Affiliation: Department of Stem Cell and Regenerative Biology, Harvard University, Cambridge, MA, USA.

ABSTRACT
Chemotherapy, irradiation, and other agents are widely used to target the process of cell division in neoplastic cells. However, while these therapies are effective against most cancers, the high proliferative rate of the cells of the hematopoietic system that produce billions of blood cells needed daily throughout life is extremely sensitive to these agents, resulting in loss of blood cell populations, which can be life threatening. Neutropenia is the most serious hematologic toxicity of chemotherapy, which can result in patient morbidity and mortality due to opportunistic infection and often is the limiting factor in dose escalation or duration of chemotherapeutic administration. Neutropenic patients often require hospitalization and incur substantial medical costs associated with anti-infective therapy. Treatment of iatrogenic and congenic neutropenia was changed in the early 1990s with the introduction of filgrastim (Neupogen(®)) and pegfilgrastim (Neulasta(®)). With the expiration of patent lives of both of these drugs, biosimilars have begun to emerge. In this review, we will summarize the chemical characteristics, pharmacokinetics, safety and efficacy of lipegfilgrastim (Lonquex(®)), the first long-acting biosimilar filgrastim to receive regulatory approval and enter the marketplace.

No MeSH data available.


Related in: MedlinePlus