title: Characterization and non-clinical assessment of the proposed etanercept biosimilar GP2015 with originator etanercept (Enbrel(®)).
abstract: Biosimilars are approved biologics that are comparable to an originator product with respect to quality, safety and efficacy. Herein, the authors describe the functional and non-clinical studies designed to determine the biosimilarity of GP2015 and originator etanercept (Enbrel®).
  
  
  
  The development of an Enbrel biosimilar (GP2015) involved extensive characterization of the originator. A step-wise target-directed and iterative technical development program involving state-of-the-art functional characterization studies and non-clinical evaluations (pharmacokinetics, pharmacodynamics and safety/toxicology) was applied with the aim of confirming that GP2015 is comparable to originator (Enbrel) at the non-clinical level.
  
  
  
  In in vitro tests, GP2015 and Enbrel had comparable binding affinities to TNF-α, C1q complement and a complete panel of Fc-Receptors. Comprehensive functional characterization testing confirmed the comparability of GP2015 with Enbrel in terms of its ability to bind to and neutralize TNF-α, which reflects the primary mechanism of action of etanercept. Non-clinical data confirmed that the proposed biosimilar to Enbrel, GP2015, is comparable with regards to its pharmacokinetic properties and pharmacodynamic activity, and efficacy as well as safety/toxicity.
  
  
  
  The proposed Enbrel biosimilar, GP2015, was shown to be comparable to its originator product in studies designed to confirm biosimilarity.
authors.affiliation: a Preclinical Development , Sandoz Biopharmaceuticals/Hexal AG , Holzkirchen , Germany.
authors.forename: Hans-Peter
authors.initials: HP
authors.lastname: Hofmann
authors.affiliation: a Preclinical Development , Sandoz Biopharmaceuticals/Hexal AG , Holzkirchen , Germany.
authors.forename: Ulrich
authors.initials: U
authors.lastname: Kronthaler
authors.affiliation: b External Bioassay Support , Novartis Pharma AG , Basel , Switzerland.
authors.forename: Cornelius
authors.initials: C
authors.lastname: Fritsch
authors.affiliation: b External Bioassay Support , Novartis Pharma AG , Basel , Switzerland.
authors.forename: Roger
authors.initials: R
authors.lastname: Grau
authors.affiliation: c Sandoz Biopharmaceuticals/Hexal AG , Holzkirchen , Germany.
authors.forename: Stefan O
authors.initials: SO
authors.lastname: Müller
authors.affiliation: d Phys. Chem. Characterization , Sandoz GmbH , Langkampfen , Austria.
authors.forename: Robert
authors.initials: R
authors.lastname: Mayer
authors.affiliation: e Global Analyt Charact. & Bioanalyt. , Hexal AG Oberhaching , Bayern , Germany.
authors.forename: Andreas
authors.initials: A
authors.lastname: Seidl
authors.affiliation: a Preclinical Development , Sandoz Biopharmaceuticals/Hexal AG , Holzkirchen , Germany.
authors.forename: Antonio
authors.initials: A
authors.lastname: Da Silva
mesh_terms: D000818:Animals; D018501:Antirheumatic Agents / Q000737:chemistry / Q000378:metabolism* / Q000627:therapeutic use; D001172:Arthritis, Rheumatoid / Q000188:drug therapy / Q000378:metabolism; D059451:Biosimilar Pharmaceuticals / Q000737:chemistry / Q000378:metabolism* / Q000627:therapeutic use; D000068800:Etanercept / Q000737:chemistry / Q000378:metabolism* / Q000627:therapeutic use; D006801:Humans; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors* / Q000378:metabolism*
chemical_list: D018501:Antirheumatic Agents; D059451:Biosimilar Pharmaceuticals; D014409:Tumor Necrosis Factor-alpha; D000068800:Etanercept
keywords: Enbrel; GP2015; TNF-α; biosimilars; disease-modifying drugs; etanercept