FRI0309 A Phase I Pharmacokinetics TRIAL Comparing PF-05280586 (A Potential Biosimilar) and Rituximab in Subjects with Active Rheumatoid Arthritis with Active Disease in TNF Failures (Reflections B328-01). (10th June 2014)

• Record Type: Journal Article
• Authors: Yin, D.; Becker, J.-C.; Melia, L.A.; Li, R.; Gumbiner, B.; Thomas, D.; Spencer-Green, G.; Meng, X.
• Is Part Of: Annals of the rheumatic diseases. Volume 73:Supplement 2(2014)
• Page Start: 497
• Page End: 497
• Publication Date: 2014-06-10
• Subjects: Rheumatism -- Periodicals; 616.723005
• DOI: 10.1136/annrheumdis-2014-eular.5444
• Languages: English
• ISSNs: 0003-4967

Abstract

Abstract : 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. DOI: 10.1136/annrheumdis-2014-eular.5444