Frontiers in Immunology (Dec 2024)

Comparative immunogenicity assessment of biosimilar natalizumab to its reference medicine: a matching immunogenicity profile

  • Paul Chamberlain,
  • Bernhard Hemmer,
  • Josef Höfler,
  • Hendrik Wessels,
  • Oliver von Richter,
  • Cyrill Hornuss,
  • Johann Poetzl,
  • Karsten Roth

DOI
https://doi.org/10.3389/fimmu.2024.1414304
Journal volume & issue
Vol. 15

Abstract

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BackgroundBiosimilar natalizumab (biosim-NTZ) is the first biosimilar monoclonal antibody of reference natalizumab (ref-NTZ) for treatment of relapsing forms of multiple sclerosis (MS). Within the totality of evidence for demonstration of biosimilarity, immunogenicity assessments were performed in healthy subjects and patients with relapsing-remitting MS (RRMS) to confirm a matching immunogenicity profile between biosim-NTZ and ref-NTZ.MethodsImmunogenicity of biosim-NTZ versus ref-NTZ was evaluated in two pivotal clinical studies. In a comparative efficacy and safety study, patients with RRMS (n=264) received monthly infusions of biosim-NTZ/EU-ref-NTZ over 48 weeks. The primary endpoint period was Week 0 to Week 24. In a separate, comparative pharmacokinetic/pharmacodynamic (PK/PD) study, healthy subjects (n=450) received a single dose of biosim-NTZ, US-ref-NTZ or EU-ref-NTZ prior to an 85-day follow-up. In both studies, state-of-the-art, highly sensitive and drug tolerant bioanalytical assays were used to identify the proportion of participants with anti-drug antibodies (ADA) and neutralizing antibodies (NAb) against natalizumab over time.ResultsIn the comparative efficacy and safety study, biosim-NTZ and EU-ref-NTZ demonstrated similar incidences of overall ADA (79.4% vs 73.7%, respectively) and NAb (68.7% vs 66.2%, respectively) at Week 24. ADA titers over time were also concordant throughout the study period. Switching treatment from EU-ref-NTZ to biosim-NTZ had no impact on treatment-related ADA/NAb or clinical responses. Likewise, the single-dose PK/PD study reported matching overall incidence of ADA between treatment groups and matching ADA titer profiles over time.ConclusionThe immunogenicity profile of biosim-NTZ was confirmed to match that of ref-NTZ in healthy subjects and patients with RRMS by applying highly sensitive methods.

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