1421: Pharmacokinetics, Safety, Tolerability, and Immunogenicity of a Proposed Tocilizumab Biosimilar (MSB11456) versus US‑licensed Tocilizumab: Results of a Randomized, Double-blind, Parallel‑group, Single‑intravenous Dose Study in Healthy Adults (APTURA II)
Monika Tomaszewska-Kiecana1, Martin Ullmann2, Emmanuelle Vincent2, Corinne Petit-frere2, Joëlle Monnet3 and Andras Illes2, 1Biokinetica S.A., Jozefow, Poland, 2Fresenius Kabi SwissBioSim, Eysins, Switzerland, 3Fresenius Kabi Swiss BioSim, Eysins, Switzerland
Background/Purpose: Tocilizumab is a biologic anti-interleukin-6 receptor monoclonal immunoglobin G1 antibody indicated for treating inflammatory diseases, including RA, and cytokine release syndrome. MSB11456 is a proposed biosimilar to US-licensed tocilizumab and EU-approved tocilizumab. This randomized, double-blind, parallel-group single-dose study (EudraCT Number 2019-003484-22) compared the pharmacokinetic (PK), safety, tolerability, and immunogenicity profiles of intravenous (IV) MSB11456 versus US-licensed tocilizumab in healthy adult volunteers. The primary objective was to demonstrate the PK equivalence of MSB11456 with US-licensed tocilizumab after a single IV infusion, following applicable guidelines from the European Medicines Agency and US Food and Drug Administration.
Methods: Healthy adults were randomized to receive MSB11456 or US-licensed tocilizumab as a single 1-hour 8 mg/kg IV infusion. Blood samples for PK and immunogenicity analyses were collected pre-dose and at scheduled time points up to day 48 post-dose. To demonstrate PK equivalence, the primary endpoint was the area under the concentration-time curve (AUC) from time zero to the last quantifiable concentration (AUC0-last). Secondary endpoints included maximum observed concentration (Cmax), AUC from time zero to infinity (AUC0-inf), additional PK and safety parameters, antidrug antibody (ADA), and neutralizing antibody (NAb) incidence (Table 1). PK equivalence between the two treatments was demonstrated if the 90% confidence interval (CI) for the geometric mean ratio (GMR) for geometric least squares mean (GLSMR) AUC0-last, was entirely contained within the 80.00% to 125.00% equivalence limits. The primary analysis was performed on natural logarithm (ln) transformed parameters using an analysis of variance model with treatment as a fixed effect.
Results: 130 subjects were randomized; 2 subjects were withdrawn prior to dosing due to adverse events. A total of 128 subjects received tocilizumab, of whom 62 received MSB11456 and 66 received US-licensed tocilizumab. Demographic characteristics of both treatment groups were similar. Primary PK endpoint analysis demonstrated equivalence between MSB11456 and US-licensed tocilizumab with 90% CI for the GLSMR AUC0-last entirely contained within the 80.00% to 125.00% equivalence limits (GLSMR [90% CI] 103.34 [98.53, 108.37]). 90% CI for the GMR for the secondary PK parameters AUC0-inf (103.15 [97.86, 108.73]), and Cmax (101.48 [97.23, 105.92]) supported the conclusion of PK equivalence. Safety, tolerability, and immunogenicity were similar between groups (Table 1).
Conclusion: After a single IV infusion of 8 mg/kg in healthy subjects, PK equivalence was demonstrated between MSB11456 and US-licensed tocilizumab for the primary and secondary PK endpoints, with similar safety, tolerability, and immunogenicity results for each product. This study supports IV MSB11456 as a proposed biosimilar to US-licensed tocilizumab. Table 1. Results of primary and secondary endpoint analyses Disclosures: M. Tomaszewska-Kiecana, None; M. Ullmann, Fresenius Kabi SwissBioSim, Fresenius Kabi SwissBioSim; E. Vincent, Fresenius Kabi SwissBioSim, Fresenius Kabi SwissBioSim; C. Petit-frere, Fresenius Kabi SwissBioSim; J. Monnet, Fresenius Kabi Swiss BioSim; A. Illes, Fresenius Kabi SwissBioSim.
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Table 1. Results of primary and secondary endpoint analyses