Background PF-05280586, a proposed biosimilar to rituximab, has the same primary amino acid sequence as rituximab with similar physicochemical and in vitro functional properties.
Objectives This study was designed to demonstrate pharmacokinetic (PK) similarity of PF-05280586 to rituximab sourced from the US (rituximab-US) and EU (rituximab-EU), and between rituximab-US and rituximab-EU. Safety was also evaluated.
Methods In this double-blind trial (NCT01526057), 220 subjects with active rheumatoid arthritis on a background of methotrexate who had an inadequate response to one or more TNF antagonist therapies were randomized 1:1:1 to one course of IV PF-05280586, rituximab-US or rituximab-EU 1000 mg on Days 1 and 15 (with stable background regimen of methotrexate). The primary analysis was the PK similarity testing using full PK profiling. PK similarity for a given test-to-reference comparison was considered demonstrated if the 90% CI of the test-to-reference ratio of the AUC from time 0 to infinity (AUC0–∞) and maximum concentration (Cmax) were within 80.00–125.00%.
Results Baseline demographics for 198 subjects evaluable for PK were similar among 3 treatment arms. The 3 study drugs exhibited similar disposition profiles and PK parameters. The 90% CI for the ratios of Cmax, AUC from time 0 to 2 weeks (AUC0–2wk) and to the last measurable time point (AUCT), and AUC0–∞ were within 80.00–125.00% for the comparisons of PF-05280586 to rituximab-US and rituximab-EU, and rituximab-EU to rituximab-US. A similar number of subjects discontinued for safety reason. 8 subjects reported serious adverse events of which 2 were considered treatment-related (rituximab-US: grade 2 atrial flutter [resolved]; rituximab-EU: grade 2 thrombocytopenic purpura [resolved although the subject was permanently discontinued from the study]).
Conclusions This study demonstrates PK similarity of PF-05280586 to both rituximab-US and rituximab-EU and rituximab-EU to rituximab-US. All 3 treatments were generally well tolerated, with a low incidence of treatment-related AEs and discontinuations due to AEs.
Disclosure of Interest D. Yin Employee of: Pfizer Inc., J.-C. Becker Employee of: Pfizer Inc., L. Melia Employee of: Pfizer Inc., R. Li Employee of: Pfizer Inc., B. Gumbiner Employee of: Pfizer Inc., D. Thomas Employee of: Pfizer Inc., G. Spencer-Green Employee of: Pfizer Inc., X. Meng Employee of: Pfizer Inc.