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

Abstract

ABP 798 is a proposed biosimilar to rituximab reference product (RP), an anti-CD20 monoclonal antibody. Pharmacokinetics (PK), pharmacodynamics (PD), and safety results from the comparative clinical study that evaluated the PK, PD, safety, efficacy, and immunogenicity of ABP 798 versus rituximab RP are presented here. Subjects with moderate to severe rheumatoid arthritis (RA) received 2 doses of ABP 798, United States-sourced RP (rituximab US) or European Unionsourced RP (rituximab EU), each consisting of two 1000-mg infusions 2 weeks apart. For the second dose (week 24), ABP 798-and rituximab EU-treated subjects received the same treatment; rituximab US-treated subjects transitioned to ABP 798. End points included area under the serum concentration-time curve from time 0 extrapolated to infinity and maximum observed serum concentration following the second infusion of the first dose (PK) and percentage of subjects with complete CD19+ cell depletion days 1-33 (PD). Primary analysis established PK similarity between ABP 798 and rituximab RP based on 90% confidence intervals of the adjusted geometric mean ratios being within a prespecified equivalence margin of 0.8 and 1.25. Complete CD19+ B-cell depletion on day 3 among groups confirmed PD similarity. These findings demonstrated PK/PD similarity between ABP 798 and rituximab RP in subjects with moderate to severe RA.

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

“…Post-baseline, immunogenicity data for the first dose period have previously been reported [12]. From day 1 through the EOS, 14 (14.4%) subjects in the ABP 798/ ABP 798 group, 13 (13.8%) subjects in the rituximab EU/ rituximab EU group, and 20 (20.6%) subjects in the rituximab US/ABP 798 group developed binding ADAs.…”

“…The first dose was admin- Subjects were monitored throughout the study for adverse events (AEs) and concomitant medication use. Clinical laboratory and vital signs were assessed at multiple time points during the study; these data are reported separately [13].…”

“…The margin was chosen based on previously published findings [ 17 , 18 ]. The approach for primary efficacy analysis of clinical equivalence depended on the results of the primary PK similarity assessment previously performed and reported [ 12 , 13 ]. Because PK similarity had been established between rituximab US and rituximab EU, data from the 2 rituximab RP treatment groups (rituximab EU and rituximab US) were combined into a single-pooled rituximab RP group.…”

“…As the next step in biosimilar development, a comparative clinical study was conducted to evaluate the similarity of ABP 798 to rituximab RP with regard to PK, PD, efficacy, safety, and immunogenicity in patients with moderate-to-severe RA. The PK equivalence and PD similarity between ABP 798 and rituximab RP (US-sourced rituximab [rituximab US] or EU-sourced rituximab [rituximab EU]) were established in patients with moderate-to-severe RA; these results have been reported separately [ 12 , 13 ].…”

Efficacy and Safety of ABP 798: Results from the JASMINE Trial in Patients with Follicular Lymphoma in Comparison with Rituximab Reference Product

“…The final steps in the development of a biosimilar include comparisons of PK, safety, immunogenicity, and efficacy between the biosimilar and the RP in human clinical trials. The PK/pharmacodynamic (PD) similarity of ABP 798 with rituximab RP has been demonstrated in a three-arm study in patients with rheumatoid arthritis [13]. The current study (JASMINE) was designed to demonstrate the clinical similarity between ABP 798 and rituximab RP in terms of efficacy, PK, PD, safety, and immunogenicity in patients with previously untreated CD20-positive (CD20+), low tumor-burden follicular lymphoma, as an appropriately sensitive population for the demonstration of clinical similarity.…”