Confirmation of Biosimilarity in a Pharmacokinetic/Pharmacodynamic Study in Healthy Volunteers for an Analytically Highly Similar Pegfilgrastim.

A phase 1 pharmacokinetic (PK) and pharmacodynamic (PD) study was conducted to demonstrate similarity of a proposed pegfilgrastim biosimilar to its reference product. In a single-dose, randomized, assessor-blinded, 2-way crossover, active-controlled PK/PD study, 66 healthy adults received the proposed pegfilgrastim biosimilar and US-licensed pegfilgrastim reference product. Primary end points were pegfilgrastim AUCt and Cmax (PK), and absolute neutrophil count AUECt and Emax (PD). Safety and immunogenicity were also measured. Fifty-six subjects completed both arms of the study. Mean pegfilgrastim concentration-time profile for both products was similar, with the 90% confidence intervals (CI) of the relative mean ratio for the primary end points falling within the predefined acceptance criteria of 80%-125% (91.7%-116.1% and 86.7%-110.2% for AUCt and Cmax , respectively). PD similarity was also demonstrated by the 95%CI of the relative mean ratio of the primary end point parameters within the predefined acceptance margins of 80%-125% (96.0%-101.6% and 92.6%-100.1% for AUECt and Emax , respectively). No statistically meaningful PK/PD differences were observed. No clinically meaningful safety or immunological differences were observed with the proposed pegfilgrastim biosimilar that were not previously identified with the reference product. The proposed pegfilgrastim biosimilar product is highly similar to the reference product with regard to PK/PD.