Eflapegrastim Enhanced Efficacy Compared to Pegfilgrastim in Neutropenic Rats Supports Potential for Same-Day Dosing

Abstract Eflapegrastim (Rolontis®) is a long-acting G-CSF with an IgG4 Fc fragment and short polyethylene glycol linker. Current G-CSF products are administered 24 hours after chemotherapy. The present study compares the duration of neutropenia (DN) with eflapegrastim or pegfilgrastim at 0, 2, 5 or 24 hours post-chemotherapy. Eflapegrastim was evaluated by G-CSF receptor-binding and bone marrow cell proliferation assays in vitro. Eflapegrastim-Fc component binding to Fcγ receptors, C1q and FcRn assessed by ELISA. Neutropenia was induced in rats via intraperitoneal cyclophosphamide or docetaxel/cyclophosphamide. Rats received chemotherapy followed by vehicle, pegfilgrastim, or eflapegrastim at 2, 5 or 24 hours. The difference in DN after treatment was assessed. In vitro binding to G-CSF receptor of both agents were similar. Binding to FcRn and no binding to Fcγ receptors or C1q was observed with eflapegrastim. Studies in chemotherapy-induced neutropenic rats showed shorter DN with eflapegrastim versus pegfilgrastim. Increased levels of G-CSF in serum and marrow were observed in eflapegrastim treated groups versus pegfilgrastim. Although eflapegrastim and pegfilgrastim have similar in vitro binding affinity, the Fc fragment in eflapegrastim increases the uptake into bone marrow resulting in increased therapeutic potential for chemotherapy-induced neutropenia. Eflapegrastim's greater marrow resident time provided a pharmacodynamic advantage over pegfilgrastim translating into shortened duration of neutropenia. Our findings support eflapegrastim same day administration with chemotherapy warranting evaluation in patients undergoing myelosuppressive chemotherapy.