Relative bioavailability of FKB327 when administered using different methods

Biosimilars/Research | Posted 14/02/2020 post-comment0 Post your comment

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].

Turkey 2016 COVER V16E31DG

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.

Permission granted to reproduce for personal and non-commercial use only. All other reproduction, copy or reprinting of all or part of any ‘Content’ found on this website is strictly prohibited without the prior consent of the publisher. Contact the publisher to obtain permission before redistributing.

Copyright – Unless otherwise stated all contents of this website are © 2020 Pro Pharma Communications International. All Rights Reserved.

comment icon Comments (0)
Post your comment
Most viewed articles
About GaBI
Home/About GaBI Posted 06/08/2009
EU guidelines for biosimilars
EMA logo 1 V13C15
Home/Guidelines Posted 08/10/2010