PF-06881893 (Nivestym™), a Filgrastim Biosimilar, Versus US-Licensed Filgrastim Reference Product (US-Neupogen(®)): Pharmacokinetics, Pharmacodynamics, Immunogenicity, and Safety of Single or Multiple Subcutaneous Doses in Healthy Volunteers

BACKGROUND: Three comparative clinical studies assessed the pharmacokinetics (PK), pharmacodynamics (PD), immunogenicity and safety of PF-06881893 (filgrastim-aafi; Nivestym™), a filgrastim biosimilar, versus US-licensed reference product (filgrastim; US-Neupogen(®)) in healthy volunteers (HVs). METHODS: Two separate open-label, crossover-design PK/PD studies were conducted: a single-dose study (n = 24) and a multiple-dose study (n = 60). In each study, HVs were randomized to Nivestym followed by US-Neupogen, or vice versa. Study drug (5 μg/kg) was administered subcutaneously as a single injection or as five consecutive daily injections. Primary PK and PD endpoints were area under the filgrastim serum concentration–time curve, maximum observed concentration, area under the effect curve (AUEC) for absolute neutrophil count (ANC), maximum observed ANC, AUEC for cluster of differentiation (CD)-34(+) count, and maximum observed CD34(+) count. In an open-label, parallel-design, non-inferiority, comparative immunogenicity study, HVs were randomized (n = 128/treatment) to Nivestym or US-Neupogen. The primary endpoint was the proportion of subjects with a negative baseline antidrug antibody (ADA) test result and one or more confirmed post-dose positive ADA result. RESULTS: Overall demographics were as follows: female (n = 162/340); White (n = 274/340), Black (n = 58/340), and other (n = 8/340); age (18–65 years); and weight (50.8–96.5 kg). All primary PK and PD endpoints met the pre-specified criteria for PK and PD equivalence. The primary endpoint in the comparative immunogenicity study met pre-specified criteria for non-inferiority. CONCLUSIONS: Nivestym demonstrated PK and PD equivalence in single and multiple subcutaneous-dose settings and non-inferiority for immunogenicity to US-Neupogen, with a comparable safety profile, supporting the demonstration of biosimilarity. TRIAL REGISTRATION: ClinicalTrials.gov C1121002 (NCT02766647); C1121003 (NCT02766634); C1121012 (NCT02923791). ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s40259-019-00343-8) contains supplementary material, which is available to authorized users.