Proposed biosimilar pegfilgrastim shows similarity in pharmacokinetics and pharmacodynamics to reference pegfilgrastim in healthy subjects

Abstract

Aims: This study aimed to demonstrate that the pharmacokinetic (PK) and pharmacodynamic (PD) profile of Sandoz proposed biosimilar pegfilgrastim (LA-EP2006) matches reference pegfilgrastim (Neulasta^® ) in healthy subjects. Safety and immunogenicity were also assessed.

Methods: The phase I, randomized, double-blind, two-period crossover study consisted of two treatment periods separated by an 8-week washout period. Healthy subjects aged 18-45 were randomized to either proposed biosimilar/reference pegfilgrastim or reference pegfilgrastim/proposed biosimilar. Proposed biosimilar and reference pegfilgrastim were administered on Day 1 of each treatment period (single 6 mg subcutaneous injection). Blood samples for PK/PD analysis were taken predose and ≤336 h postdose. PK/PD similarity was claimed if 90% (PK) and 95% (PD) confidence intervals (CI) for geometric mean ratios of the area under the serum concentration-time curve (AUC) from time of dosing and extrapolated to infinity (AUC_0-inf ), or to the last measurable concentration (AUC_0-last ), maximum observed serum concentration (C_max ), absolute neutrophil count (ANC) area under the effect curve from the time of dosing to the last measurable concentration (AUEC_0-last ) and ANC maximum effect attributable to the therapy under investigation (E_max ) were completely contained within the predefined margin (0.8 to 1.25).

Results: Overall, 169 subjects completed the study. PK/PD similarity was demonstrated; 90% CIs of geometric mean ratio of proposed biosimilar/reference for PK: AUC_0-inf (1.0559-1.2244), AUC_0-last (1.0607-1.2328), C_max (1.0312-1.1909) and 95% CIs for PD (ANC): AUEC_0-last (0.9948-1.0366), E_max (0.9737-1.0169) were completely contained within predefined margin of 0.8 to 1.25. Both biologics had similar safety profiles, were well tolerated and had low incidence of anti-drug antibodies. No neutralizing or clinically relevant antibodies were detected.

Conclusions: PK/PD similarity of Sandoz proposed biosimilar pegfilgrastim and reference pegfilgrastim was confirmed. No clinically meaningful differences in safety, tolerability and immunogenicity were observed in healthy subjects.

Keywords: drug development < phase I; oncology < chemotherapy; pharmacodynamics; pharmacokinetics.