Immunogenicity evaluation strategy for a second-generation therapeutic, PEG-IFN-β-1a.

Aims: 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.

Materials & 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.

Results & Conclusion: 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.