Comparative immunogenicity assessment of biosimilar natalizumab to its reference medicine: a matching immunogenicity profile
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 h...
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Frontiers Media S.A.
2024-12-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2024.1414304/full |
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| author | Paul Chamberlain Bernhard Hemmer Josef Höfler Hendrik Wessels Oliver von Richter Cyrill Hornuss Johann Poetzl Karsten Roth |
| author_facet | Paul Chamberlain Bernhard Hemmer Josef Höfler Hendrik Wessels Oliver von Richter Cyrill Hornuss Johann Poetzl Karsten Roth |
| author_sort | Paul Chamberlain |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-c4cac83de4564f1384504ffcaaedd5cd |
| institution | Kabale University |
| issn | 1664-3224 |
| language | English |
| publishDate | 2024-12-01 |
| publisher | Frontiers Media S.A. |
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| series | Frontiers in Immunology |
| spelling | doaj-art-c4cac83de4564f1384504ffcaaedd5cd2024-12-19T06:23:51ZengFrontiers Media S.A.Frontiers in Immunology1664-32242024-12-011510.3389/fimmu.2024.14143041414304Comparative immunogenicity assessment of biosimilar natalizumab to its reference medicine: a matching immunogenicity profilePaul Chamberlain0Bernhard Hemmer1Josef Höfler2Hendrik Wessels3Oliver von Richter4Cyrill Hornuss5Johann Poetzl6Karsten Roth7bioLOGICA Consulting, Arthez-d’Asson, FranceDepartment of Neurology, Technical University of Munich, Klinikum rechts der Isar, Munich and Munich Cluster for Systems Neurology (SyNergy), Munich, GermanyStaburo GmbH, Munich, GermanyPolpharma Biologics S.A., Gdansk, PolandHexal AG (a Sandoz company), Holzkirchen, GermanyHexal AG (a Sandoz company), Holzkirchen, GermanyHexal AG (a Sandoz company), Holzkirchen, GermanyPolpharma Biologics S.A., Gdansk, PolandBackgroundBiosimilar 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.https://www.frontiersin.org/articles/10.3389/fimmu.2024.1414304/fullnatalizumabmultiple sclerosisneutralizing antibodiesanti-drug antibodiesimmunologybiologic products |
| spellingShingle | Paul Chamberlain Bernhard Hemmer Josef Höfler Hendrik Wessels Oliver von Richter Cyrill Hornuss Johann Poetzl Karsten Roth Comparative immunogenicity assessment of biosimilar natalizumab to its reference medicine: a matching immunogenicity profile Frontiers in Immunology natalizumab multiple sclerosis neutralizing antibodies anti-drug antibodies immunology biologic products |
| title | Comparative immunogenicity assessment of biosimilar natalizumab to its reference medicine: a matching immunogenicity profile |
| title_full | Comparative immunogenicity assessment of biosimilar natalizumab to its reference medicine: a matching immunogenicity profile |
| title_fullStr | Comparative immunogenicity assessment of biosimilar natalizumab to its reference medicine: a matching immunogenicity profile |
| title_full_unstemmed | Comparative immunogenicity assessment of biosimilar natalizumab to its reference medicine: a matching immunogenicity profile |
| title_short | Comparative immunogenicity assessment of biosimilar natalizumab to its reference medicine: a matching immunogenicity profile |
| title_sort | comparative immunogenicity assessment of biosimilar natalizumab to its reference medicine a matching immunogenicity profile |
| topic | natalizumab multiple sclerosis neutralizing antibodies anti-drug antibodies immunology biologic products |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2024.1414304/full |
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