A Randomised Controlled Trial Comparing the Pharmacokinetics and Tolerability of the Proposed Adalimumab Biosimilar MSB11022 Delivered via Autoinjector and Pre-filled Syringe in Healthy Subjects

Ahad Sabet, Daniel S Dickerson, Eugenia E Kunina, Anna Lucia Buccarello, Joëlle Monnet, Ahad Sabet, Daniel S Dickerson, Eugenia E Kunina, Anna Lucia Buccarello, Joëlle Monnet

Abstract

Introduction: The aim of the study was to demonstrate the bioequivalence, and compare the safety and tolerability of MSB11022, a proposed biosimilar of adalimumab, when delivered by either an autoinjector (AI) or a pre-filled syringe (PFS).

Methods: In this pharmacokinetic (PK), parallel group, open-label study, 216 healthy volunteers were randomised 1:1 to receive a single subcutaneous injection of a 40 mg/0.8 mL dose of MSB11022 administered via AI or PFS. Coprimary PK endpoints were maximum observed concentration (Cmax), area under the concentration-time curve (AUC) from time 0 to the last quantifiable concentration (AUC0-t), and AUC from time 0 extrapolated to infinity (AUC0-inf). PK equivalence between the AI and PFS administration methods was declared if the 90% confidence intervals (CIs) for the ratio of geometric least square means was entirely contained within the 80-125% equivalence margin for all coprimary endpoints. Safety and tolerability were also evaluated.

Results: The 90% CI for the three coprimary PK endpoints (Cmax, AUC0-t and AUC0-inf) were entirely contained within the predefined equivalence margins of 80-125%. Mean serum concentration-time profiles were similar following injection via AI or PFS. Treatment-emergent adverse events (TEAEs) were comparable across both treatment groups. Study device-related TEAEs were reported by 11.3% and 13.1% of subjects in the AI and PFS treatment groups, respectively. Study drug-related TEAEs were reported by 28.3% and 34.6% of subjects in the AI and PFS treatment groups, respectively. Few subjects experienced injection-site reactions, mainly pain and erythema, regardless of the administration method.

Conclusion: Delivery of MSB11022 via an AI is bioequivalent to delivery via a PFS. The safety and tolerability profile of MSB11022 was comparable across administration methods. The development of an AI for MSB11022 provides a choice of self-injection devices available to patients, potentially improving treatment compliance.

Trial registration: ClinicalTrials.gov trial identifier: NCT04018599.

Keywords: Adalimumab; Autoinjector; Bioequivalence; Biosimilar; Pharmacokinetic; Phase 1; Tumour necrosis factor.

© 2022. The Author(s).

Figures

Fig. 1
Fig. 1
Study design. AI Autoinjector, EOS end of study, PFS pre-filled syringe, PK pharmacokinetic, R 1:1 randomisation
Fig. 2
Fig. 2
Autoinjector presentation
Fig. 3
Fig. 3
Participant disposition. AI autoinjector, Cmax maximum observed concentration, PFS pre-filled syringe, PK pharmacokinetic. aThree randomised participants did not receive MSB11022 for the following reasons: infection (AI group: n = 1); nausea and vomiting (AI group: n = 1); and positive drug screen (PFS group: n = 1). bFive treated participants were excluded from the PK analysis set for the following reasons: insufficient concentration–time data to derive at least one PK parameter (PFS group: n = 2; AI group: n = 1); pre-dose serum concentration > 5% of Cmax (PFS group: n = 1); and incomplete dosing (AI group: n = 1). Cmax Maximum observed concentration
Fig. 4
Fig. 4
Mean (SD) serum concentration of MSB11022 on a linear scale (a) and a semi-logarithmic scale (b) following a single 40 mg subcutaneous injection via an autoinjector or a pre-filled syringe (PK analysis set). Data are arithmetic mean. LLOQ = 300 ng/mL; samples below the LLOQ before the last quantifiable data point were set to 0. Concentrations below the LLOQ after the last quantifiable data point were considered as missing. LLOQ Lower limit of quantification, PK pharmacokinetic, SD standard deviation

References

    1. EMC. Humira 40 mg/0.4 ml pre-filled syringe and pre-filled pen. Summary of product characteristics (SmPC). 2021. . Accessed 8 Nov 2021.
    1. US FDA. HUMIRA® (adalimumab) injection, for subcutaneous use. 2021. . Accessed 8 Nov 202l.
    1. EMC. Idacio 40 mg solution for injection in pre-filled pen. Summary of product characteristics (SmPC). 2021. . Accessed 11 Feb 2021.
    1. EMA. Idacio – EPAR all authorised presentations. . Accessed 11 Feb 2021.
    1. Australian Government: Department of Health. Therapeutic Goods Administration: Idacio. 2020. . Accessed 11 Feb 2021.
    1. New Zealand Government. New Zealand data sheet: Idacio 40 mg adalimumab (rch) solution for injection. 2020. . Accessed 11 Feb 2021.
    1. Fresenius Kabi. Fresenius Kabi Canada launches IDACIO® (adalimumab injection) a biosimilar to HUMIRA® (adalimumab) for the treatment of multiple chronic inflammatory conditions. 2021. . Accessed 24 Feb 2022.
    1. Magnenat L, Palmese A, Fremaux C, et al. Demonstration of physicochemical and functional similarity between the proposed biosimilar adalimumab MSB11022 and Humira®. MAbs. 2017;9(1):127–139. doi: 10.1080/19420862.2016.1259046.
    1. Hyland E, Mant T, Vlachos P, et al. Comparison of the pharmacokinetics, safety, and immunogenicity of MSB11022, a biosimilar of adalimumab, with Humira® in healthy subjects. Br J Clin Pharmacol. 2016;82(4):983–993. doi: 10.1111/bcp.13039.
    1. Hercogová J, Papp KA, Chyrok V, Ullmann M, Vlachos P, Edwards CJ. AURIEL-PsO: a randomized, double-blind phase III equivalence trial to demonstrate the clinical similarity of the proposed biosimilar MSB11022 to reference adalimumab in patients with moderate-to-severe chronic plaque-type psoriasis. Br J Dermatol. 2020;182(2):316–326. doi: 10.1111/bjd.18220.
    1. Edwards CJ, Monnet J, Ullmann M, Vlachos P, Chyrok V, Ghori V. Safety of adalimumab biosimilar MSB11022 (acetate-buffered formulation) in patients with moderately-to-severely active rheumatoid arthritis. Clin Rheumatol. 2019;38(12):3381–3390. doi: 10.1007/s10067-019-04679-y.
    1. Maniadakis N, Toth E, Schiff M, et al. A targeted literature review examining biologic therapy compliance and persistence in chronic inflammatory diseases to identify the associated unmet needs, driving factors, and consequences. Adv Ther. 2018;35(9):1333–1355. doi: 10.1007/s12325-018-0759-0.
    1. Rubin DT, Mittal M, Davis M, Johnson S, Chao J, Skup M. Impact of a patient support program on patient adherence to adalimumab and direct medical costs in Crohn’s disease, ulcerative colitis, rheumatoid arthritis, psoriasis, psoriatic arthritis, and ankylosing spondylitis. J Manag Care Spec Pharm. 2017;23(8):859–867.
    1. van den Bemt BJF, Gettings L, Domańska B, Bruggraber R, Mountian I, Kristensen LE. A portfolio of biologic self-injection devices in rheumatology: how patient involvement in device design can improve treatment experience. Drug Deliv. 2019;26(1):384–392. doi: 10.1080/10717544.2019.1587043.
    1. Kivitz A, Cohen S, Dowd JE, et al. Clinical assessment of pain, tolerability, and preference of an autoinjection pen versus a prefilled syringe for patient self-administration of the fully human, monoclonal antibody adalimumab: the TOUCH trial. Clin Ther. 2006;28(10):1619–1629. doi: 10.1016/j.clinthera.2006.10.006.
    1. Demary W, Schwenke H, Rockwitz K, et al. Subcutaneously administered methotrexate for rheumatoid arthritis, by prefilled syringes versus prefilled pens: patient preference and comparison of the self-injection experience. Patient Prefer Adherence. 2014;8:1061–1071.
    1. Hsiao B, Fraenkel L. Patient preferences for rheumatoid arthritis treatment. Curr Opin Rheumatol. 2019;31(3):256–263. doi: 10.1097/BOR.0000000000000591.
    1. Borrs-Blasco J, Gracia-Prez A, Rosique-Robles JD, Caster MDE, Abad FJ. Acceptability of switching adalimumab from a prefilled syringe to an autoinjection pen. Expert Opin Biol Ther. 2010;10(3):301–307. doi: 10.1517/14712590903530633.
    1. Ghil J, Zielińska A, Lee Y. Usability and safety of SB5 (an adalimumab biosimilar) prefilled syringe and autoinjector in patients with rheumatoid arthritis. Curr Med Res Opin. 2019;35(3):497–502. doi: 10.1080/03007995.2018.1560211.
    1. 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):1405–1415. doi: 10.1111/bcp.13245.
    1. Ramael S, Van Hoorick B, Tiessen R, et al. Similar pharmacokinetics of the adalimumab (Humira®) biosimilar BI 695501 whether administered via subcutaneous autoinjector or prefilled syringe (VOLTAIRE®-AI and VOLTAIRE®-TAI): Phase 1, randomized, open-label, parallel-group trials. Rheumatol Ther. 2018;5(2):403–421. doi: 10.1007/s40744-018-0119-1.
    1. Schwarzenbach F, Trong MD, Grange L, et al. Results of a human factors experiment of the usability and patient acceptance of a new autoinjector in patients with rheumatoid arthritis. Patient Prefer Adherence. 2014;8:199–209. doi: 10.2147/PPA.S50583.

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