title: Immunogenicity evaluation strategy for a second-generation therapeutic, PEG-IFN-β-1a.
abstract: OBJECTIVE
  Neutralizing antibodies can diminish clinical efficacy of IFN-β in multiple sclerosis patients. Therefore, monitoring immunogenicity was considered critical during clinical development of a second-generation, pegylated IFN-β product, PEG-IFN-β-1a.
  
  
  METHODS
  Assays previously used to evaluate immunogenicity of IFN-β-1a were used to assess PEG-IFN-β-1a immunogenicity, with modifications to apply current best bioanalytical practices. A separate testing paradigm was used to monitor antibodies to polyethylene glycol.
  
  
  CONCLUSIONS
  Final assay cut points and relevant titer levels were established in-study. Immunogenicity evaluation strategies for second-generation therapeutics should take into consideration current best bioanalytical practices while retaining consistency with legacy assays to facilitate data comparison and interpretation. This study illustrates challenges in assessing immunogenicity of second-generation therapeutics.
authors.affiliation: Biogen, 22 Binney Street, Cambridge, MA 02142, USA.|EMD Serono, Billerica, MA 01821, USA.
authors.forename: Joleen T
authors.initials: JT
authors.lastname: White
authors.affiliation: Biogen, 22 Binney Street, Cambridge, MA 02142, USA.
authors.forename: Mary
authors.initials: M
authors.lastname: Crossman
authors.affiliation: Biogen, 22 Binney Street, Cambridge, MA 02142, USA.
authors.forename: Kelly
authors.initials: K
authors.lastname: Richter
authors.affiliation: Biogen, 22 Binney Street, Cambridge, MA 02142, USA.
authors.forename: Melissa
authors.initials: M
authors.lastname: Berman
authors.affiliation: Biogen, 22 Binney Street, Cambridge, MA 02142, USA.
authors.forename: Jaya
authors.initials: J
authors.lastname: Goyal
authors.affiliation: Biogen, 22 Binney Street, Cambridge, MA 02142, USA.
authors.forename: Meena
authors.initials: M
authors.lastname: Subramanyam
mesh_terms: D057134:Antibodies, Neutralizing / Q000276:immunology*; D017326:Clinical Trials, Phase III as Topic; D004311:Double-Blind Method; D006801:Humans; D016899:Interferon-beta / Q000276:immunology / Q000494:pharmacology*; D015337:Multicenter Studies as Topic; D009103:Multiple Sclerosis / Q000276:immunology* / Q000628:therapy; D011092:Polyethylene Glycols / Q000494:pharmacology*; D016032:Randomized Controlled Trials as Topic
chemical_list: D057134:Antibodies, Neutralizing; D011092:Polyethylene Glycols; D016899:Interferon-beta; C428112:peginterferon beta-1a