Efficacy, safety, and immunogenicity of proposed biosimilar RGB-19 and tocilizumab intravenously administered to adults with active rheumatoid arthritis and an inadequate response to methotrexate: a phase 3, randomised study.

Objectives: This phase 3 study (jRCT2031220512) evaluated the equivalence in efficacy, and compared the serum concentration, pharmacodynamics, safety, and immunogenicity of proposed biosimilar RGB-19 and tocilizumab in adults with active rheumatoid arthritis (RA). Methods: Participants were randomly assigned 1:1 to intravenous infusions of 8 mg/kg RGB-19 or tocilizumab every 4 weeks, with efficacy evaluated to week 52 and safety follow-up to week 54. The primary endpoint was the mean change from baseline (CfB) in Disease Activity Score based on 28 joints with erythrocyte sedimentation rate (DAS28-ESR), with equivalence determined if the 2-sided 95% CI for the pooled difference between groups was within the predefined equivalence margin (±0.6 at week 12). Secondary objectives were other efficacy indicators, serum drug concentration, pharmacodynamics, safety, and immunogenicity. Results: In total, 368 participants were randomly assigned to treatment (RGB-19 N = 182; tocilizumab N = 186). At week 12, the difference in mean DAS28-ESR CfB between groups (RGB-19 n = 173; tocilizumab n = 181) was -0.21 (95% CI: -0.43, 0.02; within the equivalence margin). All other efficacy indicators and serum drug concentration values were similar between groups up to week 52. Median absolute neutrophil count, C-reactive protein, and soluble interleukin-6 receptor values were similar between groups to week 52. Safety profiles were similar, with a similar incidence of treatment-emergent adverse events and adverse drug reactions to week 54. The incidence of treatment-emergent antidrug and neutralising antibodies was similarly low in both groups. Conclusions: This study demonstrated equivalent efficacy, and similar safety and immunogenicity, of RGB-19 and reference tocilizumab for participants with active RA.