title: Demonstration of Functional Similarity of Proposed Biosimilar ABP 501 to Adalimumab.
abstract: BACKGROUND
  Due to the complex molecular structure and proprietary manufacturing processes of monoclonal antibodies (mAbs), differences in structure and function may be expected during development of biosimilar mAbs. Important regulatory requirements for approval of biosimilar products involve comprehensive assessments of any potential differences between proposed biosimilars and reference mAbs, including differences in all known mechanisms of action, using sensitive and relevant methods. Any identified structural differences should not result in differences in biofunctional or clinical activity.
  
  
  OBJECTIVE
  A comprehensive assessment comparing the Amgen biosimilar candidate ABP 501 with FDA-licensed adalimumab (adalimumab [US]) and EU-authorized adalimumab (adalimumab [EU]) was conducted to demonstrate similarity in biofunctional activity.
  
  
  METHODS
  The functional similarity assessment included testing of binding kinetics to soluble tumor necrosis factor α (TNFα) and relative binding to transmembrane TNFα. The neutralization of TNFα-induced caspase activation, TNFα- and lymphotoxin-α (LTα)-induced chemokine production, and cytotoxicity was also tested. Binding to Fc-gamma receptors FcγRIa, FcγRIIa (131H), FcγRIIIa (158V and 158F), and neonatal Fc receptor (FcRn) was compared with the reference mAbs, as was antibody-dependent cell-mediated cytotoxicity and complement-dependent cytotoxicity.
  
  
  RESULTS
  The data demonstrate that ABP 501 is similar to both adalimumab (US) and adalimumab (EU) with respect to evaluated biofunctional activities.
  
  
  CONCLUSIONS
  Similarity in biofunctional activity is a critical component of the totality of evidence required for demonstration of biosimilarity. The functional similarity demonstrated for ABP 501 comprehensively assesses the known mechanisms of action of adalimumab, supporting the conclusion that ABP 501, adalimumab (US), and adalimumab (EU) are likely to be clinically similar.
authors.affiliation: Amgen, Inc., One Amgen Center Drive, Thousand Oaks, CA, 91320, USA.
authors.forename: Jyoti
authors.initials: J
authors.lastname: Velayudhan
authors.affiliation: Amgen, Inc., One Amgen Center Drive, Thousand Oaks, CA, 91320, USA.
authors.forename: Yuh-Feng
authors.initials: YF
authors.lastname: Chen
authors.affiliation: Amgen, Inc., One Amgen Center Drive, Thousand Oaks, CA, 91320, USA.
authors.forename: Amanda
authors.initials: A
authors.lastname: Rohrbach
authors.affiliation: Amgen, Inc., One Amgen Center Drive, Thousand Oaks, CA, 91320, USA.
authors.forename: Christina
authors.initials: C
authors.lastname: Pastula
authors.affiliation: Amgen, Inc., One Amgen Center Drive, Thousand Oaks, CA, 91320, USA.
authors.forename: Gwen
authors.initials: G
authors.lastname: Maher
authors.affiliation: Amgen, Inc., One Amgen Center Drive, Thousand Oaks, CA, 91320, USA.
authors.forename: Heather
authors.initials: H
authors.lastname: Thomas
authors.affiliation: Amgen, Inc., One Amgen Center Drive, Thousand Oaks, CA, 91320, USA.
authors.forename: Ryan
authors.initials: R
authors.lastname: Brown
authors.affiliation: Amgen, Inc., One Amgen Center Drive, Thousand Oaks, CA, 91320, USA. bornt@amgen.com.
authors.forename: Teresa L
authors.initials: TL
authors.lastname: Born
mesh_terms: D000068879:Adalimumab / Q000378:metabolism / Q000494:pharmacology*; D000818:Animals; D000920:Antibody-Dependent Cell Cytotoxicity; D059451:Biosimilar Pharmaceuticals / Q000378:metabolism / Q000494:pharmacology*; D016466:CHO Cells / Q000187:drug effects; D003412:Cricetulus; D015395:Histocompatibility Antigens Class I / Q000378:metabolism; D006801:Humans; D008233:Lymphotoxin-alpha / Q000494:pharmacology; D011961:Receptors, Fc / Q000378:metabolism; D017452:Receptors, IgG / Q000378:metabolism; D020349:Surface Plasmon Resonance; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000378:metabolism* / Q000494:pharmacology
chemical_list: D059451:Biosimilar Pharmaceuticals; C080568:Fc gamma receptor IIA; D015395:Histocompatibility Antigens Class I; D008233:Lymphotoxin-alpha; D011961:Receptors, Fc; D017452:Receptors, IgG; D014409:Tumor Necrosis Factor-alpha; D000068879:Adalimumab; C100688:Fc receptor, neonatal