Background PK bioequivalence of BI 695501, a biosimilar candidate, and the adalimumab originator was demonstrated previously (VOLTAIRE®-PK: Wynne et al., Expert Opin Investig Drugs 2016;25:1361–70) and led to further clinical development.
Objectives To demonstrate clinical equivalence of BI 695501 with the adalimumab originator by comparing efficacy, safety and immunogenicity using a clinical model sensitive to detect potential differences between the two biologics.
Methods In this 58-week, multi-national, multicentre, randomised, double-blind, parallel arm Phase III study (NCT02137226), 645 pts (18–80 years) with moderate to severe active RA on stable treatment with methotrexate were randomised to receive US-licensed SC adalimumab originator or BI 695501 40mg Q2W for 24 weeks. At Wk 24, pts on adalimumab originator were re-randomised to continue the adalimumab originator or switch to BI 695501 until Wk 48. Pts on BI 695501 were dummy re-randomised. Co-primary end points were proportion of pts achieving ACR20 at Wks 12 and 24. Equivalence between BI 695501 and the adalimumab originator was demonstrated if the relevant confidence intervals (CI) for differences in ACR20 response rate at Wks 12 and 24 were within the predefined margins (Wk 12: 90% CI –12%, 15%; Wk 24: 95% CI –15%, 15%). The secondary efficacy end point was change from baseline in DAS28-ESR at Wks 12 and 24. Safety and immunogenicity were exploratory objectives. Wk 48/58 data will be reported later.
Results The co-primary end points of ACR20 response at Wks 12 and 24 were within the pre-defined criteria for equivalence, demonstrating clinical equivalence between BI 695501 and the adalimumab originator (Table 1).
The proportion of pts with treatment-emergent adverse events (TEAE) was similar between the BI 695501 and the adalimumab originator treatment groups (Table 2).
Rates of serious AEs and discontinuation due to TEAEs were similar across the groups. No deaths were reported during the study. Similar frequencies of pts tested positive for anti-drug antibodies (BI 695501 43.2%; adalimumab originator 47.8%), and neutralising antibodies (BI 695501 16.0%; adalimumab originator 20.6%) in both groups at Week 24.
Conclusions This study in pts with RA demonstrated that BI 695501 and the adalimumab originator are highly similar in terms of efficacy, safety and immunogenicity.
Disclosure of Interest : S. Cohen Grant/research support from: Amgen, Boehringher Ingelheim, Coherus, Pfizer, Consultant for: Amgen, Boehringher Ingelheim, Celltrion, Merck, Pfizer, Sandoz, A. Alonso-Ruiz: None declared, P. Klimiuk: None declared, E. Lee: None declared, N. Peter Employee of: Boehringer Ingelheim, I. Sonderegger Employee of: Boehringer Ingelheim, D. Assudani Employee of: Boehringer Ingelheim