Comparative Nonclinical Assessments of the Proposed Biosimilar PF-05280586 and Rituximab (MabThera®). (October 2014)

• Record Type: Journal Article
• Authors: Ryan, Anne M.; Sokolowski, Sharon A.; Ng, Chee-Keng; Shirai, Norimitsu; Collinge, Mark; Shen, Amy C.; Arrington, Joshua; Radi, Zaher; Cummings, Thomas R.; Ploch, Stephen A.; Stephenson, Sarah A.; Tripathi, Niraj K.; Hurst, Susan I.; Finch, Gregory L.; Leach, Michael W.
• Is Part Of: Toxicologic pathology. Volume 42:Number 7(2014:Oct.)
• Page Start: 1069
• Page End: 1081
• Publication Date: 2014-10
• Subjects: rituximab -- potential biosimilar -- nonclinical safety -- B cells -- cynomolgus monkey -- anti-CD20 -- monoclonal antibody.; Pathology -- Periodicals; Toxicology -- Periodicals; Pathology; Toxicology; 615.9
• DOI: 10.1177/0192623313520351
• Languages: English
• ISSNs: 0192-6233

Abstract

Comparative nonclinical studies were conducted with the proposed biosimilar PF-05280586 and rituximab-EU (MabThera®). In side-by-side analyses, peptide maps and complement-dependent cytotoxicity assay results were similar. Sexually-mature cynomolgus monkeys were administered PF-05280586 or rituximab-EU as a single dose of 0, 2, 10, or 20 mg/kg on day 1 and observed for 92 days (single-dose study) or as 5 weekly injections of 0 or 20 mg/kg and necropsied on day 30, the day after the 5th dose, or on day 121 (repeat-dose study). The pharmacokinetic and pharmacodynamic profiles for both molecules were similar. Marked depletion of peripheral blood B cells 4 days after dosing was followed by near or complete repletion (single-dose study) or partial repletion (repeat-dose study). In the single-dose study, anti-drug antibodies (ADA) were detected by day 29 in all animals administered PF-05280586 or rituximab-EU and persisted through day 85, the last day tested. In the repeat-dose study, ADA were detected on day 121 in 50% of animals administered PF-05280586 or rituximab-EU. Both molecules were well tolerated at all doses. In all endpoints evaluated, PF-05280586 exhibited similarity to rituximab-EU.