GlycoPEGylated Filgrastim XM22 Demonstrates Dose-Dependent Activity in Comparison to Pegfilgrastim in a Dose-Escalating Study in Healthy Volunteers after Body-Weight Dependent Single Dose.

XM22 is a glycoPEGylated recombinant human G-CSF that interacts with the G-CSF receptor by binding and activation. In pilot studies in non-neutropenic animals, XM22 demonstrated a similar PK/PD profile compared to pegfilgrastim. Because of its longer duration of action compared to filgrastim, XM22 is intended to be dosed once per cycle for the reduction of duration of severe neutropenia and incidence of febrile neutropenia in cancer patients undergoing chemotherapy.

METHODS: A single center, randomized, single-blind study of XM22, administered as single escalating body-weight (bw) dependent doses given by the s.c. route was conducted to assess safety, pharmacokinetic profile and pharmacodynamic properties based on absolute neutrophil count (ANC) and CD34+ cell count. Male or female healthy volunteers were assigned to one of 3 XM22 dose groups, at 25 μg/kg bw dose (n=8), at 50 μg/kg bw (n=15), and 100 μg/kg bw (n=15) compared to 100 μg/kg bw pegfilgrastim (n=15).

RESULTS: 53 healthy volunteers were enrolled in the three dose groups and completed 21 day follow-up. Injections were generally well-tolerated with no discontinuations due to adverse events or serious adverse events. XM22 at a dose of 100 μg/kg bw exhibited a PK profile with increased bioavailability and extended half life compared to the same dose of pegfilgrastim. ANC area over baseline effect curve (AOBEC) and CD34+ AOBEC were higher after treatment with XM22 100 μg/kg bw (6818.55 hr*neut./nl and 7340.16 hr*cell count/μl geometric mean respectively) compared to the same dose of pegfilgrastim. Antibody data will be presented.

CONCLUSIONS: Single body-weight dependent doses up to 100 mg/kg of XM22 administered to healthy volunteers were generally well-tolerated with regard to the expected side effect profile and demonstrated dose-dependent increases in absolute neutrophil count and CD34+ cell count. These data supplement results from another study in healthy volunteers in which XM22 was administered as a fixed dose.