Efficacy and safety results from a randomized double-blind study comparing proposed biosimilar ABP 798 with rituximab reference product in subjects with moderate-to-severe rheumatoid arthritis

Abstract

Background/objectives ABP 798 is a proposed biosimilar to the originator biologic rituximab, an anti-CD20 monoclonal antibody. This comparative clinical study evaluated the pharmacokinetics (PK), safety, and efficacy of ABP 798 versus rituximab reference product (RP) in patients with moderate-to-severe rheumatoid arthritis (RA). Methods Adults with moderate-to-severe RA with an inadequate response or intolerance to other disease-modifying anti-rheumatic drugs including 1 or more tumor necrosis factor inhibitor therapies (n = 311) received ABP 798, US-sourced rituximab RP (rituximab US), or EU-sourced rituximab RP (rituximab EU) (1000 mg, 2 weeks apart). At week 24, ABP 798- or rituximab EU-treated subjects received a second dose of the same treatment, while rituximab US-treated subjects transitioned to receive ABP 798. The key efficacy endpoint was DAS28-CRP change from baseline at week 24. Other efficacy endpoints included DAS28-CRP at other time points; ACR20, ACR50, and ACR70 criteria; and hybrid ACR. The rituximab RP groups were pooled for all efficacy endpoints since PK equivalence had been established between rituximab US and rituximab EU. Results Clinical equivalence between ABP 798 and rituximab RP was established as the 90% confidence interval for DAS28-CRP change from baseline at week 24 fell within the prespecified equivalence margin (− 0.6, 0.6). Safety and immunogenicity profiles of ABP 798 were comparable across treatment groups and not affected by single transition from RP to ABP 798. Conclusions Clinical equivalence in terms of efficacy, safety, and immunogenicity was established between ABP 798 and rituximab RP in this comparative clinical trial in patients with moderate-to-severe RA. Key Points• ABP 798 provided similar efficacy as rituximab reference product (RP) in patients with moderate-severe rheumatoid arthritis.• The safety and immunogenicity profiles for ABP 798 were similar to those for the rituximab RP.• The single transition from rituximab RP to ABP 798 did not show differences in efficacy, safety, or immunogenicity.

A Randomized, Double‐Blind Study Comparing Pharmacokinetics and Pharmacodynamics of Proposed Biosimilar ABP 798 With Rituximab Reference Product in Subjects With Moderate to Severe Rheumatoid Arthritis

“…The results presented here demonstrate that ABP 798 has PK/PD similar to rituximab RP in patients with active moderate to severe RA on a background of MTX who had an inadequate response or intolerance to 1 or more TNF antagonist therapies. Importantly, top‐line safety, and immunogenicity were similar in ABP 798 and rituximab RP; detailed safety results are presented elsewhere 18 . Given that human PK/PD studies are fundamental components establishing similarity between a proposed biosimilar and the originator RP during biosimilar development, these results support the clinical development of ABP 798 as a proposed biosimilar to rituximab.…”

“…Importantly, top-line safety, and immunogenicity were similar in ABP 798 and rituximab RP; detailed safety results are presented elsewhere. 18 Given that human PK/PD studies are fundamental components establishing similarity between a proposed biosimilar and the originator RP during biosimilar development, these results support the clinical development of ABP 798 as a proposed biosimilar to rituximab. IP, investigational product; N, subjects with a binding negative or no result at baseline and at least a postbaseline result; n, number of subjects with event.…”