title: Pharmacokinetics, safety, tolerability and immunogenicity of FKB327, a new biosimilar medicine of adalimumab/Humira, in healthy subjects.
abstract: To compare the pharmacokinetics, safety, tolerability and immunogenicity of FKB327, a biosimilar of adalimumab, with European Union (EU)-approved Humira and US-licensed Humira after single subcutaneous doses in healthy subjects.
  
  
  
  In a randomized, double-blind, parallel-group study, 180 healthy subjects received by subcutaneous injection 40 mg of EU-Humira, or US-Humira, or FKB327, in a 1:1:1 ratio, stratified by bodyweight. Pharmacokinetics, local tolerability, immunogenicity, adverse events, vital signs, electrocardiography and laboratory safety tests were assessed prior to and up to 1536 h after treatment.
  
  
  
  The pharmacokinetics of FKB327 were similar to those of both EU- and US-Humira. The 90% confidence interval for the ratios of AUC0-t, AUC0-inf, and Cmaxgeometric means were in the acceptance range for bioequivalence of 0.80-1.25 for all three pairwise comparisons by analysis of covariance with baseline characteristics age, body weight and (for Cmaxonly) sex as covariates. Tolerability of all three treatments was equally acceptable, and there were no differences in safety profile or immunogenicity among the three treatments. Overall, antidrug antibodies were detected in approximately 70% of subjects who received each treatment; higher titres were associated with faster elimination of adalimumab.
  
  
  
  The study demonstrated pharmacokinetic similarity of FKB327 with EU- and US-Humira. FKB327 was well tolerated by healthy subjects, with adverse effects similar to Humira. If clinical similarity to Humira, including efficacy, can be shown in patients, FKB327 will meet the criteria for biosimilarity to Humira.
authors.affiliation: Hammersmith Medicines Research Ltd., London, UK.
authors.forename: Adeep
authors.initials: A
authors.lastname: Puri
authors.affiliation: Hammersmith Medicines Research Ltd., London, UK.
authors.forename: Andrew
authors.initials: A
authors.lastname: Niewiarowski
authors.affiliation: Fujifilm Kyowa Kirin Biologics Co, Ltd., Tokyo, Japan.
authors.forename: Yasumasa
authors.initials: Y
authors.lastname: Arai
authors.affiliation: Fujifilm Kyowa Kirin Biologics Co, Ltd., Tokyo, Japan.
authors.forename: Hideaki
authors.initials: H
authors.lastname: Nomura
authors.affiliation: Quanticate Ltd., Hitchin, UK.
authors.forename: Mark
authors.initials: M
authors.lastname: Baird
authors.affiliation: Quanticate Ltd., Hitchin, UK.
authors.forename: Isobel
authors.initials: I
authors.lastname: Dalrymple
authors.affiliation: Hammersmith Medicines Research Ltd., London, UK.
authors.forename: Steve
authors.initials: S
authors.lastname: Warrington
authors.affiliation: Hammersmith Medicines Research Ltd., London, UK.
authors.forename: Malcolm
authors.initials: M
authors.lastname: Boyce
mesh_terms: D000068879:Adalimumab / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics*; D056704:Adaptive Immunity / Q000187:drug effects*; D000328:Adult; D018501:Antirheumatic Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology*; D019540:Area Under Curve; D059451:Biosimilar Pharmaceuticals / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics*; D004311:Double-Blind Method; D004562:Electrocardiography; D005260:Female; D064368:Healthy Volunteers; D006339:Heart Rate / Q000187:drug effects; D006801:Humans; D007279:Injections, Subcutaneous; D008297:Male; D008875:Middle Aged; D013810:Therapeutic Equivalency; D055815:Young Adult
chemical_list: D018501:Antirheumatic Agents; D059451:Biosimilar Pharmaceuticals; D000068879:Adalimumab
keywords: FKB327; Humira; TNF-α; adalimumab; biosimilar; monoclonal