While multiple guidelines provide recommendations for the use of tocilizumab to treat rheumatoid and juvenile idiopathic arthritis, none have recommendations for the biosimilar agent. The most recent guideline publication was from 2022, which would not have been updated with the recent FDA approval of Tofidence [1], [2], [3]
Due to the lack of published data on the Phase 3 trial evaluating the interchangeability between Tofidence (tocilizumab-bavi; BAT1806/BIIB800) and reference tocilizumab (TCZ), the manufacturer Biogen was contacted to request further information regarding the Phase 3 trial leading to FDA approval of Tofidence. The medical information department further disclosed that the requested data cannot be shared at the current time point but did reference the published poster/abstract on preliminary results. Specifically, a 2022 phase 3 randomized, double-blinded, active-controlled trial, as part of the biosimilar development program, evaluated the efficacy, pharmacokinetics (PK), safety, and immunogenicity of BAT1806/BIIB800 in comparison with European Union (EU)-sourced TCZ in subjects with moderate to severe rheumatoid arthritis with inadequate response to methotrexate (MTX). [4], [5], [6]
A total of 621 eligible patients recruited from 55 centres in China and Europe were randomized (2:1:1) to one of three treatment groups: (1) BAT1806/BIIB800 up to Week 48 (n= 312), (2) TCZ up to Week 48 (n= 155), or (3) TCZ up to Week 24, followed by BAT1806/BIIB800 from Week 24 to Week 48 (n= 154), administered intravenously every 4 weeks at a dose of 8mg/kg. Baseline characteristics were similar across all treatment groups. Results demonstrated comparable proportions of subjects achieving an American College of Rheumatology (ACR)20 response in BAT1806/BIIB800 vs.TCZ groups, both at Week 12 (68.97% vs. 64.82%) and Week 24 (69.89% vs. 67.94%). The corresponding differences between ACR response rates were 4.15% (95% confidence interval [CI] -3.63 to 11.93) at week 12, and 1.94% (90% CI -4.04 to 7.92; 95% CI -5.18 to 9.07) at Week 24, which achieved the pre-defined equivalence margin per FDA (90% CI -12.0%/+15%). Additionally, serum trough levels (15.8 vs. 15.4 mcg/mL), incidence of treatment-emergent adverse events (TEAEs; 64.4% vs. 63.4%), and proportion of antidrug antibody (ADA)-positive patients (20.5% vs. 13.6%) were found to be similar between the biosimilar and reference products. [5], [6]
Subsequent treatment period 2 reporting results from Weeks 24 to 48 included 90 (92.9%), 142 (92.2%), and 145 (93.5%) in groups 1, 2, and 3, respectively. Proportions of ACR20 responders continued to increase up to 253/280 (90.4%), 121/134 (90.3%), and 122/139 (87.8%) for groups 1, 2, and 3, respectively. Again, the incidence of serious TEAEs was similar between treatment groups (2.8% vs. 3.5% vs. 2.8%), and no death occurred. ADAs were reported at least once in 21.0%, 16.2%, and 18.6% of subjects in treatment groups 1, 2, and 3, respectively; of these subjects, all but 1 in the TCZ group tested positive for neutralizing antibodies. Collectively, results from the phase 3 trials concluded comparable efficacy, safety, immunogenicity, and PK profiles between BAT1806, TCZ/BAT1806, and TCZ. In individuals switching from TCZ to BAT1806, no safety or clinically relevant immunogenicity issues were observed. [5], [6]