Comparison of the PK, PD, safety, tolerability, and immunogenicity of proposed biosimilar RGB-19 and tocilizumab in healthy Japanese males: a phase 1, randomised, crossover study

Objectives RGB-19 is a proposed biosimilar to tocilizumab. This phase 1 study assessed the equivalence in pharmacokinetics (PKs) and compared the pharmacodynamics (PDs), safety, and immunogenicity of a single subcutaneous administration of RGB-19 and tocilizumab. Methods Healthy Japanese males aged 20 to 40 years were included in this 2-period, 2-sequence crossover study. Participants were randomised 1:1 to RGB-19 162 mg or tocilizumab 162 mg in period 1 (day -1 to day 42), before crossing over treatment in period 2 (day 42 to day 85). The primary objective was to assess equivalence between treatments in the maximum serum drug concentration (Cmax) and area under the serum drug concentration curve from 0 hours to infinity (AUCinf) using predefined 2-sided 90% CI criteria of 0.80 to 1.25. Secondary objectives included assessment of PK, PD, safety, tolerability, and immunogenicity. Results In period 1, 110 participants were included, followed by 102 participants in period 2. PK equivalence was demonstrated between treatments for Cmax and AUCinf (Cmax point estimate: 1.04 [90% CI: 0.98-1.10]; AUCinf point estimate: 1.05 [90% CI: 0.97-1.13]). Concentration-time profiles for PD parameters were similar between treatments. Antidrug antibody (ADA) and neutralising antibody incidences were similar between treatments, and ADA status had no impact on PK, PD, or safety outcomes. There were no notable differences in treatment-emergent adverse events or adverse drug reactions. Conclusions This study demonstrated equivalence in PK and similarity in PD, immunogenicity, and safety of RGB-19 and tocilizumab. These data suggest RGB-19 provides a similar therapeutic benefit to tocilizumab.