Establishing Biosimilarity

Phase I Clinical Study in Healthy Volunteers:

A randomized, double-blind, single-dose, 3-arm, parallel study demonstrated the similar pharmacokinetic profile of TOFIDENCE vs Actemra1*

Study Design

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N=138 enrolled
(n=129 receiving
a single IV dose)
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Baseline to
Day 57
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Phase I, randomized, double-blind, three-arm, parallel group PK study comparing a single IV dose of TOFIDENCE (4 mg/kg body weight) with EU- and US-sourced Actemra* in healthy volunteers.
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Assessed PK with AUCO-inf, AUC0-t, Cmax, Tmax, t1/2, Vz, and CL. Safety profile and immunogenicity.
EU-Actemra US-Actemra Adapted from: Fu et al. 2020.

Mean serum concentration time curves were similar for TOFIDENCE and Actemra1†

Adapted from: Zhang et al. 2021.

Actemra (US-sourced reference tocilizumab) and RoActemra (EU-sourced reference tocilizumab).

Phase I Clinical Study Summary in Healthy Volunteers

A randomized, double-blind, single-dose, 3-arm, parallel clinical study comparing the tolerance, immunogenicity, and pharmacokinetics of TOFIDENCE and EU- and US-sourced Actemra in healthy volunteers.1

  • This Phase I study demonstrated similar PK profiles of TOFIDENCE with EU-Actemra and US-Actemra when administered at a dose of 4 mg/kg as a single intravenous infusion
  • The PK characteristics of TOFIDENCE were comparable to those of EU-Actemra and US-Actemra
    • The 90% confidence intervals (CIs) of the ratio of the geometric means (GMRs) of the treatments comparing the AUC0-∞, Cmax, and AUC0-t for TOFIDENCE and EU- and US-sourced Actemra were in the range of 86.90–106.15%, which was within the predefined bioequivalence range of 80–125%.
  • The safety profile of TOFIDENCE was comparable to reference tocilizumab
    • TOFIDENCE, EU-Actemra, and US-Actemra demonstrated similar safety and immunogenicity profiles
    • There were no reported SAEs, and local reactions were absent (study of healthy participants)


A Phase III study further evaluated the safety and efficacy of TOFIDENCE in a cohort of patients with RA.2

Actemra (US-sourced reference tocilizumab) and RoActemra (EU-sourced reference tocilizumab).

Help start a movement for more patients

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ADA=antidrug antibody; AE=adverse event; ANOVA=analysis of variance; AUC0-t=area under the curve from zero to the final quantifiable concentration; AUC0–∞=area under the curve from zero to infinity; CL=clearance; Cmax=maximum observable serum concentration; GMR=geometric mean ratio; IV=intravenous; PK=pharmacokinetic; SAE=serious adverse events; Tmax=the concentration-time data included time to peak; t1/2=half-life, Vz=volume of distribution.

References
  1. Zhang H, Wang H, Wei H, et al. A phase l clinical study comparing the tolerance, immunogenicity, and pharmacokinetics of proposed biosimilar BAT1806 and reference tocilizumab in healthy Chinese men. Front Pharmacol. 2021;11:609522. 
  2. Leng X, Leszczyński P, Jeka S, et al. Comparing tocilizumab biosimilar BAT1806/BIIB800 with reference tocilizumab in patients with moderate-to-severe rheumatoid arthritis with an inadequate response to methotrexate: a phase 3, randomised, multicentre, double-blind, active-controlled clinical trial. Lancet Rheumatol. 2024;6(1):e40-e50.