FKB327 is a biosimilar of Humira (adalimumab), a recombinant, human immunoglobulin G1 monoclonal antibody specific for human tumour necrosis factor alpha (TNF-α). The European Medicines Agency approved FKB327, as Hulio, in 2018 [1].
A previous study in a randomized, double-blind, parallel-group of healthy volunteers compared the pharmacokinetics (PK), safety, tolerability and immunogenicity of FKB327 with EU-approved Humira and US-licensed Humira [2]. Results from that study demonstrated that the PK, prevalence of anti-drug antibodies (ADAs) and elimination half-life of FKB327 were similar to EU-Humira and US-Humira. FKB327 was found to be well-tolerated, with a safety profile similar to both Humira formulations.
The primary objective of this study was to assess the relative bioavailability (assessed by PK parameters) of a subcutaneous (SC) dose of FKB327 administered via a pre-filled syringe (PFS), a pre-filled autoinjector (AI) or a vial with a disposable syringe (vial). Secondary objectives were to compare the safety of FKB327 across the 3 methods of administration and evaluate the effect of body weight and injection site (abdomen vs thigh) on the PK of FKB327 [3].
The study was designed as a randomized, open-label, parallel-group, single SC-dose study, conducted in 195 healthy male and female subjects. Subjects were randomized 1:1:1 to receive FKB327 40 mg via PFS, AI or vial. The primary PK parameters, area under the serum concentration-time curve to the last detectable value (AUC0-t), area under the serum concentration-time curve extrapolated to infinity (AUC0-∞) and maximum concentration (Cmax) were compared. Relative bioavailability was established if the ratio of the least squares means of the test product was within the pre-defined bioequivalence (BE) range of 0.80 to 1.25 of the reference product for each comparison. Safety and immunogenicity were also assessed.
The mean serum concentration-time profiles of FKB327 were similar following a single SC 40 mg dose administered via PFS, AI and vial. FKB327 was absorbed slowly across all 3 methods of administration, with a median tmax (time taken to reach Cmax) of 120.0 h, 144.0 h and 120.03 h for the PFS, AI and vial groups, respectively. The 90% confidence intervals (CIs) for all PK parameters (AUC0-t, AUC0-∞ and Cmax) were fully contained within the BE range for PFS compared with vial. For the AI/vial and AI/PFS comparisons, the 90% CIs were fully contained within the BE range for AUC0-∞ and Cmax. However, the upper limits for AUC0-t were slightly outside the BE limit of 0.80 to 1.25 (1.11 [0.976, 1.254] and 1.11 [0.981, 1.26], respectively). The 90% CIs for the secondary parameter of t1/2 were fully contained within the BE range for all 3 comparisons. The secondary analysis of PK parameters by body weight showed a tendency for greater exposure to FKB327 in the 50 kg to 75 kg group compared with the > 75 kg to 100 kg group, and the secondary analysis of PK parameters by injection site showed a tendency for lower exposure in the abdominal group compared with the thigh group. The proportion of subjects with positive ADA status at pre-dose was disproportionate (19.0%, 10.6% and 21.2% in the PFS, AI and vial groups, respectively). However, at subsequent time points, the proportion of positive ADA status was nearly equal in all 3 groups. At the last time point, the percentage of subjects with positive ADA activity was 100% for the vial and PFS groups and 98.5% for the AI group. The most common treatment-emergent adverse events (TEAEs; reported by ≥ 5% of subjects in any treatment group) were nasopharyngitis (25.1%), headache (9.2%), cough (4.6%), oropharyngeal pain (4.1%), and injection-site rash (2.1%). All TEAEs were considered mild or moderate, with the clear majority (94.6%) considered mild. There were no clinically meaningful findings in vital signs or 12-lead electrocardiograms (ECGs) for any subjects during the study.
In this study, the relative bioavailability of FKB327 following a single SC 40 mg dose delivered across all 3 methods of administration was highly similar based on the analysis of the PK parameters. The ADA and t1/2 of adalimumab were also similar across all 3 methods of administration. In addition, FKB327 was well-tolerated whether delivered via PFS, AI or vial. The results from this study suggest that the delivery of FKB327 with a PFS, AI or vial can be used interchangeably in clinical practice.
Conflict of interest
The authors of the research paper [3] declared that the study was was sponsored by Fujifilm Kyowa Kirin Biologics Co Ltd; editorial support via The Lynx Group LLC was proved by Mylan Inc. For full details of the authors’ conflict of interest, see the research paper [3].
Abstracted by Ms Eileen Houlihan, The Lynx Group, LLC, USA.
References
1. GaBI Online - Generics and Biosimilars Initiative. Biosimilars approved in Europe [www.gabionline.net]. Mol, Belgium: Pro Pharma Communications International; [cited 2020 Feb 14]. Available from: www.gabionline.net/Biosimilars/General/Biosimilars-approved-in-Europe
2. Puri A, Niewiarowski A, Arai Y, et al. Pharmacokinetics, safety, tolerability and immunogenicity of FKB327, a new biosimilar medicine of adalimumab/Humira, in healthy subjects. Br J Clin Pharmacol. 2017;83(7):1405-15.
3. Bush J, Kawakami K, Muniz R. A phase 1, randomized, open-label, single-dose study to assess the relative bioavailability of a subcutaneous dose of FKB327 when administered using a prefilled syringe, a prefilled auto-injector, or a vial with disposable syringe in healthy subjects. BMC Pharmacol Toxicol. 2019;20(1):87. doi:10.1186/s40360-019-0376-9.
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