Background/Purpose: ABP 798 is being developed as a biosimilar to rituximab, a CD20-directed cytolytic antibody that is approved in the US and EU for treatment of moderate-to-severe RA (US), severe RA (EU), non-Hodgkin’s lymphoma, chronic lymphocytic leukemia, granulomatosis with polyangiitis and microscopic polyangiitis, and moderate-to-severe pemphigus vulgaris (US). A phase 1-phase 3 study was conducted to evaluate the pharmacokinetics (PK), safety and efficacy of ABP 798 in comparison with rituximab reference product (RP) in patients with moderate-to-severe RA. The key efficacy and safety results of this trial comparing ABP 798 with rituximab RP are presented here.

Methods: This was a randomized, double-blind, active-controlled study conducted in adult subjects with moderate-to-severe RA who had an inadequate response or intolerance to other DMARDs. Subjects were randomized (1:1:1) to receive 2 IV infusions of 1000 mg, 2 weeks apart as first dose of either ABP 798, rituximab sourced from the US (rituximab US), or rituximab sourced from the EU (rituximab EU). At Week 24, subjects in ABP 798 and rituximab EU arms received the second dose of the same treatment, while those in the rituximab US arm transitioned to receive ABP 798 for their second dose.

The key efficacy endpoint was defined as the evaluation of change from baseline at Week 24 in DAS28-CRP. Other efficacy endpoints included ACR20, ACR50, and ACR70 at Week 24. Since PK similarity was established between rituximab US and rituximab EU (results presented separately), the 2 rituximab RP arms were pooled for efficacy equivalence assessment.

Results: A total of 311 subjects were randomized (ABP 798, n=104; rituximab EU, n=104; rituximab US, n=103); all subjects were treated with at least one infusion of investigational product. Clinical equivalence between ABP 798 and rituximab RP was established with the 90% confidence interval (CI; -0.225, 0.264) and 95% CI (-0.273, 0.312) for DAS28-CRP change from baseline at Week 24 being within the prespecified equivalence margin of (-0.6, 0.6). The 90% and 95% CIs for the mean differences between ABP 798 and the individual rituximab RP arms were also within the pre-defined margin. Over the first 24 weeks, results from other efficacy endpoints (ACR20, ACR50, ACR70) also supported clinical similarity. Overall safety and immunogenicity profiles of ABP 798 were consistent with that reported for rituximab RP with no unexpected events over this period. Treatment-emergent adverse events (TEAEs) were reported in 50%, 42.3%, and 42.7% of patients that received ABP 798, rituximab EU, and rituximab US, respectively. Infusion reactions including hypersensitivity was the most common event of interest reported. Binding antibodies developed in 13.4%, 10.6%, and 19.6% of patients that received ABP 798, rituximab EU, and rituximab US, respectively; and neutralizing antibodies in 8.2%, 2.1%, and 8.2%, respectively.

Conclusion: Based on the results of this study. clinical equivalence of ABP 798 to rituximab RP was established for efficacy and safety in subjects with moderate-to-severe RA.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/efficacy-and-safety-results-from-a-randomized-double-blind-study-that-compared-the-proposed-biosimilar-abp-798-with-rituximab-in-subjects-with-moderate-to-severe-ra/