A comparative multi-tiered immunogenicity assessment of biosimilar pegylated filgrastim: validation of methods for clinical assessment of INTP5. (1st February 2022)

• Record Type: Journal Article
• Authors: Hajela, Pallavi; Patel, Ronak; Kale, Prashant; Kumar, Manish; Khambhampaty, Sridevi
• Is Part Of: Expert opinion on biological therapy. Volume 22:Number 2(2022)
• Page Start: 321
• Page End: 330
• Publication Date: 2022-02-01
• Subjects: Immunogenicity -- ADA -- NAB -- neutralizing antibody assay -- biosimilar -- pegfilgrastim -- validation; Gene therapy -- Periodicals; Protein drugs -- Periodicals; Peptide drugs -- Periodicals; Immunotherapy -- Periodicals; Drug delivery systems -- Periodicals; 615.5
• DOI: 10.1080/14712598.2022.2006630
• Languages: English
• ISSNs: 1471-2598

Abstract

ABSTRACT: Background and Objective: Validated and highly sensitive assays are required for comparative assessment of immunogenicity of biosimilars. For INTP5, a biosimilar pegylated filgrastim, the immunogenicity assessment included tiers that allowed for assessment of antibodies against the PEG and the Filgrastim moieties for comparative clinical immunogenicity assessment. Methods: Electrochemiluminescence immunoassay (ECLIA) was used for Screening, Specificity, and Titer assays for detecting anti-drug antibodies (ADAs) and cell-based method for neutralizing ADAs. The methods were validated to enable use of same methods irrespective of biosimilar or reference arms. Results: The ADA and cell-based assay for neutralizing antibody detection were validated with a sensitivity capable of detecting binding Anti-Pegfilgrastim antibody at ~40 ng/mL and Neutralizing antibody at ~380 ng/mL and used for a comparative immunogenicity study. Of 194 subjects, 10 subjects had confirmed positive anti-drug-antibody in the biosimilar arm and 9 in the reference arm. None of the subjects were detected with neutralizing anti-drug antibodies. Conclusion: This work demonstrates the application of a rigorous approach toward validation of assays for immunogenicity studies for biosimilars. Highly sensitive, precise, and robust assays were used to conclude comparable low incidences of anti-drug antibodies in both biosimilar and innovator arms of the clinical study for Pegfilgrastim.