Lipegfilgrastim a Possible Alternative for Managing Chemotherapy-Induced Neutropenia

Filgrastim, lenograstim, and pegfilgrastim are some of the most common current granulocyte colony-stimulating factors (G-CSFs) used in clinical practice, but a recent analysis published in Biologics: Targets and Therapy, found that a new long-acting G-CSF—lipegfilgrastim—may also be promising in the management of chemotherapy-induced neutropenia.

CSFs help prevent chemotherapy-induced neutropenia and febrile neutropenia, a state of high fever and decreased neutrophils as a result of chemotherapy (especially from treatments containing anthracycline plus cyclosphosphamide, or anthracycline plus taxane). Chemotherapy-induced neutropenia and febrile neutropenia can result in life-threatening infection or sepsis and antibiotic treatment or hospitalization—which makes it so important for a viable treatment to be established for chemotherapy patients. G-CSFs such as filgrastim have proven effective by stimulating neutrophil proliferation and differentiation, and allowed for chemotherapeutic agents to be administered to patients at more optimal doses and durations with lower risks.

Filgrastim is a recombinant G-CSF produced in E. coli, while lenograstim is a glycosylated recombinant G-CSF derived from hamster ovary cells that may be more stable and active than filgrastim. Both are short acting and require daily subcutaneous injections after each cycle of chemotherapy.

Pegfilgrastim is created by attaching a covalent polyethylene glycol chain to the N-terminal of filgrastim, which makes the pegfilgrastim larger in mass and slows its degradation and clearance compared with filgrastim. Randomized Phase III trials proved the safety and efficacy of pegfilgrastim and suggested that, in comparison of the daily G-CSFs, pegfilgrastim works just as effectively as filgrastim.

Like pegfilgrastim, the novel molecule lipefilgrastim is a pegylated recombinant G-CSF. Randomized trials have shown it to be equivalent to pegfilgrastim in reducing the incidence of neutropenia in patients with breast cancer and have a similar safety profile. The study also evaluated various pharmacokinetic and pharmacodynamics properties of lipegfilgrastim, including cumulative exposure, peak exposure, time to maximum serum concentration, initial baseline effect on absolute neutrophil count, and adverse effects.

Findings from the analysis included a higher cumula­tive exposure and peak exposure for lipegfilgrastim than pegfilgrastim, and longer terminal elimination half-life for lipegfilgrastim than the terminal elimination half-life for pegfilgrastim. The safety of both was similar and no serious adverse events occurred in either.

The results of these trials demonstrate that lipegfilgrastim is relatively equivalent to pegfilgrastim in the management of chemotherapy-induced neutropenia, at least in the setting of breast cancer.

“Lipegfilgrastim is a promising alternative to pegfilgrastim when a long-acting G-CSF is considered the best choice,” the authors concluded.