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ORIGINAL RESEARCH article
Front. Immunol.
Sec. Comparative Immunology
Volume 15 - 2024 |
doi: 10.3389/fimmu.2024.1414304
Comparative immunogenicity assessment of biosimilar natalizumab to its reference medicine: A matching immunogenicity profile
Provisionally accepted
Paul Chamberlain
1
Bernhard Hemmer
2
Josef Höfler
3
Hendrik Wessels
4
Oliver von Richter
5*
Cyrill Hornuss
5
Johann Poetzl
5*
Karsten Roth
4*- 1 bioLOGICA Consulting, Arthez-d’Asson, France
- 2 Department of Neurology, Technical University of Munich, Klinikum rechts der Isar, Munich & Munich Cluster for Systems Neurology (SyNergy), Munich, Germany
- 3 Staburo GmbH, Munich, Bavaria, Germany
- 4 Polpharma Biologics S.A., Gdansk, Poland
- 5 Hexal AG (a Sandoz company), Holzkirchen, Germany
Background: Biosimilar 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. Methods: Immunogenicity 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. Results: In 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.The 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.
Keywords: natalizumab, Multiple Sclerosis, neutralizing antibodies, Anti-drug antibodies, immunology, Biologic products, biosimilar, Immunogenicity
Received: 08 Apr 2024; Accepted: 22 Nov 2024.
Copyright: © 2024 Chamberlain, Hemmer, Höfler, Wessels, von Richter, Hornuss, Poetzl and Roth. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence:
Oliver von Richter, Hexal AG (a Sandoz company), Holzkirchen, Germany
Johann Poetzl, Hexal AG (a Sandoz company), Holzkirchen, Germany
Karsten Roth, Polpharma Biologics S.A., Gdansk, Poland
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