XM02, the first granulocyte colony-stimulating factor biosimilar, is safe and effective in reducing the duration of severe neutropenia and incidence of febrile neutropenia in patients with non-Hodgkin lymphoma receiving chemotherapy.

Recombinant granulocyte colony-stimulating factors (G-CSFs) such as filgrastim or lenograstim are being used to treat chemotherapy-induced neutropenia. The aim of the present study was to investigate a new G-CSF, XM02, in comparison to filgrastim in terms of safety and efficacy in the prevention of chemotherapy-induced neutropenia in non-Hodgkin-lymphoma (NHL). A total of 92 patients receiving chemotherapy were randomised in cycle 1 to treatment with daily injections (subcutaneous 5 microg/kg/day) of XM02 (n = 63) or filgrastim (n = 29) for at least 5 days and a maximum of 14 days. In subsequent cycles, all patients received XM02. The mean duration of severe neutropenia (DSN) was 0.5 and 0.9 days in cycle 1 for XM02 and filgrastim, respectively (p = 0.1055). In cycle 1, the incidence of febrile neutropenia (FN) was 11.1% for XM02 and 20.7% for filgrastim (p = 0.1232). The adverse event profile was similar between XM02 and filgrastim. XM02 demonstrated equivalent efficacy and similar safety profile as the reference medication filgrastim. Treatment with XM02 is as beneficial as filgrastim in ameliorating severe neutropenia and FN in patients with NHL receiving chemotherapy. XM02 is safe and well tolerated in the doses applied in this study.

Bioequivalence of two recombinant granulocyte colony-stimulating factor products after subcutaneous injection in healthy volunteers.

OBJECTIVE: The objective of the study was the demonstration of bioequivalence of two recombinant human granulocyte colony-stimulating factor (G-CSF) formulations after subcutaneous administration of 5 microg/kg and 10 microg/kg comparing their pharmacokinetic and pharmacodynamic profiles in healthy subjects. METHODS: This was a randomized, single dose, two-period cross-over, two-arm study with a 14 days wash-out period. In total 56 subjects were included, 28 in each dosage cohort (5 microg/kg and 10 microg/kg). Using a 1 : 1 : 1 : 1 randomization ratio, subjects were randomly assigned to one of four possible treatment-sequence groups. A single dose of test formulation (XM02) and reference product (Neupogen, F. Hoffmann - La Roche, Ltd.) were injected. The serum G-CSF concentrations were measured by enzyme-linked immunosorbent assay (ELISA) during 48 hours after injection. The absolute Neutrophil Count (ANC) was determined by automated hematology analyzer Coulter STKSTM (Beckman Coulter, Inc.) up to 96 hours after injection. The primary pharmacokinetic (AUC0-48, AUC0- yen and Cmax) and pharmacodynamic (ANC AUC0-96, ANC AUC0- yen and ANCmax) variables were considered bioequivalent if the 90% confidence intervals (CI) were in the bioequivalence range of 80 - 125%. RESULTS: 50 subjects completed the study: 24 subjects in 5 microg/kg and 26 in 10 microg/kg dosage groups. The pharmacokinetic and pharmacodynamic parameters in 5 mg/kg and 10 mg/kg group for both formulations were very close to each other. Single doses of test and reference formulations were well tolerated. The most frequent AEs were: headache, erythrocyturia and myalgia. The incidence of AEs was equally distributed across dosage and treatment groups. CONCLUSION: The study results demonstrated the bioequivalence of two body weight-dependent doses of XM02, a new formulation of filgrastim, and the reference product Neupogen after administration of a 5 microg/kg b.w. and 10 microg/kg b.w. with respect to pharmacokinetic, pharmacodynamic and safety profiles.

XM02 is superior to placebo and equivalent to Neupogen in reducing the duration of severe neutropenia and the incidence of febrile neutropenia in cycle 1 in breast cancer patients receiving docetaxel/doxorubicin chemotherapy.

BACKGROUND: Recombinant granulocyte colony-stimulating factors (G-CSFs) such as Filgrastim are used to treat chemotherapy-induced neutropenia. We investigated a new G-CSF, XM02, and compared it to Neupogen after myelotoxic chemotherapy in breast cancer (BC) patients. METHODS: A total of 348 patients with BC receiving docetaxel/doxorubicin chemotherapy were randomised to treatment with daily injections (subcutaneous 5 microg/kg/day) for at least 5 days and a maximum of 14 days in each cycle of XM02 (n = 140), Neupogen (n = 136) or placebo (n = 72). The primary endpoint was the duration of severe neutropenia (DSN) in cycle 1. RESULTS: The mean DSN in cycle 1 was 1.1, 1.1, and 3.9 days in the XM02, Neupogen, and placebo group, respectively. Superiority of XM02 over placebo and equivalence of XM02 with Neupogen could be demonstrated. Toxicities were similar between XM02 and Neupogen. CONCLUSION: XM02 was superior to placebo and equivalent to Neupogen in reducing DSN after myelotoxic chemotherapy.