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

BioDrugs. 2019 Apr;33(2):207-220. doi: 10.1007/s40259-019-00343-8.

Abstract

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).

Publication types

  • Randomized Controlled Trial

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Area Under Curve
  • Biosimilar Pharmaceuticals / administration & dosage*
  • Biosimilar Pharmaceuticals / adverse effects
  • Biosimilar Pharmaceuticals / blood
  • Biosimilar Pharmaceuticals / pharmacokinetics*
  • Cross-Over Studies
  • Female
  • Filgrastim / administration & dosage*
  • Filgrastim / adverse effects
  • Filgrastim / immunology
  • Filgrastim / pharmacokinetics*
  • Healthy Volunteers
  • Humans
  • Injections, Subcutaneous
  • Male
  • Middle Aged
  • Neutrophils / drug effects
  • Therapeutic Equivalency
  • Young Adult

Substances

  • Biosimilar Pharmaceuticals
  • Filgrastim

Associated data

  • ClinicalTrials.gov/NCT02766647
  • ClinicalTrials.gov/NCT02766634
  • ClinicalTrials.gov/NCT02923791