title: Comparative nonclinical assessments of the proposed biosimilar PF-05280586 and rituximab (MabThera®).
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.
authors.affiliation: Drug Safety Research and Development, Pfizer Inc., Groton, Connecticut, USA anne.m.ryan@pfizer.com.
authors.forename: Anne M
authors.initials: AM
authors.lastname: Ryan
authors.affiliation: Drug Safety Research and Development, Pfizer Inc., Groton, Connecticut, USA.
authors.forename: Sharon A
authors.initials: SA
authors.lastname: Sokolowski
authors.affiliation: Biotherapeutics Pharmaceutical Sciences, Pfizer Inc., Andover, Massachusetts, USA.
authors.forename: Chee-Keng
authors.initials: CK
authors.lastname: Ng
authors.affiliation: Drug Safety Research and Development, Pfizer Inc., Groton, Connecticut, USA.
authors.forename: Norimitsu
authors.initials: N
authors.lastname: Shirai
authors.affiliation: Drug Safety Research and Development, Pfizer Inc., Groton, Connecticut, USA.
authors.forename: Mark
authors.initials: M
authors.lastname: Collinge
authors.affiliation: Drug Safety Research and Development, Pfizer Inc., Groton, Connecticut, USA.
authors.forename: Amy C
authors.initials: AC
authors.lastname: Shen
authors.affiliation: Covance Laboratories Inc., Madison, Wisconsin, USA.
authors.forename: Joshua
authors.initials: J
authors.lastname: Arrington
authors.affiliation: Drug Safety Research and Development, Pfizer Inc., Cambridge, Massachusetts, USA.
authors.forename: Zaher
authors.initials: Z
authors.lastname: Radi
authors.affiliation: Drug Safety Research and Development, Pfizer Inc., Groton, Connecticut, USA.
authors.forename: Thomas R
authors.initials: TR
authors.lastname: Cummings
authors.affiliation: Covance Laboratories Inc., Madison, Wisconsin, USA.
authors.forename: Stephen A
authors.initials: SA
authors.lastname: Ploch
authors.affiliation: Covance Laboratories Inc., Madison, Wisconsin, USA.
authors.forename: Sarah A
authors.initials: SA
authors.lastname: Stephenson
authors.affiliation: Covance Laboratories Inc., Madison, Wisconsin, USA.
authors.forename: Niraj K
authors.initials: NK
authors.lastname: Tripathi
authors.affiliation: Pharmacodynamics and Metabolism, Pfizer Inc., Groton, Connecticut, USA.
authors.forename: Susan I
authors.initials: SI
authors.lastname: Hurst
authors.affiliation: Drug Safety Research and Development, Pfizer Inc., Groton, Connecticut, USA.
authors.forename: Gregory L
authors.initials: GL
authors.lastname: Finch
authors.affiliation: Drug Safety Research and Development, Pfizer Inc., Andover, Massachusetts, USA.
authors.forename: Michael W
authors.initials: MW
authors.lastname: Leach
mesh_terms: D000818:Animals; D058846:Antibodies, Monoclonal, Murine-Derived / Q000008:administration & dosage* / Q000493:pharmacokinetics*; D018951:Antigens, CD20 / Q000378:metabolism; D001402:B-Lymphocytes / Q000187:drug effects / Q000378:metabolism; D059451:Biosimilar Pharmaceuticals / Q000008:administration & dosage / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D023381:Endpoint Determination; D005260:Female; D008252:Macaca fascicularis; D008297:Male; D015203:Reproducibility of Results; D000069283:Rituximab
chemical_list: D058846:Antibodies, Monoclonal, Murine-Derived; D018951:Antigens, CD20; D059451:Biosimilar Pharmaceuticals; D000069283:Rituximab
keywords: B cells; anti-CD20; cynomolgus monkey; monoclonal antibody.; nonclinical safety; potential biosimilar; rituximab