Pharmacokinetic and pharmacodynamic bioequivalence study of a pegfilgrastim biosimilar INTP5 in healthy subjects.

ABSTRACT

PURPOSE: This study compared pharmacokinetics, pharmacodynamics, safety and immunogenicity profiles of INTP5 (a potential pegfilgrastim biosimilar) with that of Neulasta®. METHODS: In this randomised, assessor-blind, crossover study, 344 healthy subjects received single subcutaneous dose of both INTP5 and Neulasta at 3 mg/0.3 ml (n = 172) or 6 mg/0.6 ml (n = 172) dose. The primary endpoints were AUC0-t, AUC0-∞ and Cmax of pegfilgrastim; and AUEC0-t and Emax of absolute neutrophil count (ANC). RESULTS: All 344 subjects dosed were included in the safety and immunogenicity analyses, and 292 subjects in the pharmacokinetic and pharmacodynamic analyses. At 6 mg dose, test to reference ratio (90% CI) of AUC0-t was 105.65% (99.60-112.06%), AUC0-∞ was 105.72% (99.55-112.28%) and Cmax was 103.62% (98.19-109.35%); while test to reference ratio (95% CIs) of ANC AUEC0-t was 100.79% (97.75-103.92%) and Emax was 98.70% (95.52-101.98%). Both the primary endpoints met the bioequivalence criteria (CIs within 80-125%). Similarly, at 3 mg dose, these endpoints were within the acceptance range of 80-125%. CD34+ profiles were similar and 95% CIs were within acceptance range at both doses. Adverse events were reported in 54 (15.7%; 8.72% in INTP5 vs. 8.39% in Neulasta) subjects; most events were mild. The incidences of anti-drug antibodies were low and similar between INTP5 and Neulasta and no neutralising antibodies were detected. CONCLUSIONS: Pharmacokinetic and pharmacodynamic bioequivalence was established between INTP5 and Neulasta following 3 and 6 mg doses. Safety and immunogenicity profiles were similar between INTP5 and Neulasta.