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 (only US). A phase 1‑phase 3 study was conducted to evaluate the pharmacokinetics (PK), pharmacodynamics (PD), safety, and efficacy of ABP 798 in comparison with rituximab reference product (RP) in patients with moderate-to-severe RA. Here, we report the results of PK and PD similarity of ABP 798 versus rituximab RP.

Methods: This was a randomized, double-blind, active-controlled study conducted in adult subjects with moderate-to-severe RA who have 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 of first dose of either ABP 798, rituximab RP sourced from the US (rituximab US), or rituximab RP sourced from the EU (rituximab EU). After Week 24, subjects continued treatment with ABP 798 or rituximab EU. The primary endpoint was area under the serum concentration-time curve [AUC] from time 0 extrapolated to infinity [AUC_inf] and the maximum observed serum concentration [C_max2] following the 2^nd infusion of 1^st dose; secondary PK endpoints were AUC from time 0 on Day 1 prior to the 1^st infusion of the 1^st dose to 14 days post-dose (AUC_{0-14 day}), AUC from time 0 to week 12 (AUC_{0-12 wk}), and C_max1 following the 1^st infusion of the 1^st dose. The PD was evaluated based on the percent of subjects with complete depletion in CD19+ cell count from Day 1 to Day 3.

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. For the primary PK endpoints, the study established PK similarity between ABP 798, rituximab (US) and rituximab (EU) based on 90% confidence intervals (CIs) of the adjusted geometric mean ratio (GMR) for AUC_inf and C_max2 following the 2^nd infusion of 1^st dose being within prespecified equivalence margin of 0.8 and 1.25. PK similarity was also established between rituximab US and rituximab EU for AUC_inf and C_max2 following the 2^nd infusion of 1^st dose. In addition, 90% CIs for the GMR for the secondary PK parameters (AUC_{0-14 day}, AUC_{0-12 wk}, and C_max1 following the 1^st infusion of the 1^st dose) were also within the (0.8, 1.25) margin, supporting PK similarity. PD effects of complete CD19+ B-cell depletion were similar between ABP 798 and rituximab RP arms, with 92/97 (94.8%), 93/96 (96.9%), and 90/97 (92.8%) subjects showing complete B-cell depletion in ABP 798, rituximab EU, and rituximab US arms, respectively.

Conclusion: Results of this study demonstrated PK similarity of ABP 798 to rituximab RP in subjects with moderate-to-severe RA. The PD of ABP 798 and rituximab RP were also found to be similar.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/a-randomized-double-blind-study-comparing-pharmacokinetics-pk-and-pharmacodynamics-pd-of-abp-798-with-rituximab-in-subjects-with-moderate-to-severe-ra/