{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,2]],"date-time":"2026-11-02T20:05:02Z","timestamp":1793649902579,"version":"4.5.1"},"reference-count":31,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2024,12,19]],"date-time":"2024-12-19T00:00:00Z","timestamp":1734566400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>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.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>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.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>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.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>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.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fimmu.2024.1414304","type":"journal-article","created":{"date-parts":[[2024,12,19]],"date-time":"2024-12-19T01:24:40Z","timestamp":1734571480000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":10,"title":["Comparative immunogenicity assessment of biosimilar natalizumab to its reference medicine: a matching immunogenicity profile"],"prefix":"10.3389","volume":"15","author":[{"given":"Paul","family":"Chamberlain","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bernhard","family":"Hemmer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Josef","family":"H\u00f6fler","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hendrik","family":"Wessels","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Oliver","family":"von Richter","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cyrill","family":"Hornuss","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Johann","family":"Poetzl","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karsten","family":"Roth","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2024,12,19]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1016\/j.msard.2023.104841","article-title":"A place for biosimilars in the changing multiple sclerosis treatment landscape","volume":"77","author":"Greenberg","year":"2023","journal-title":"Mult Scler Relat Disord"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1007\/s40120-019-0145-0","article-title":"Biosimilar drugs for multiple sclerosis: an unmet international need or a regulatory risk","volume":"8","author":"Rivera","year":"2019","journal-title":"Neurol Ther"},{"key":"B3","doi-asserted-by":"publisher","first-page":"593","DOI":"10.1177\/1352458512460604","article-title":"Clinical relevance of serum natalizumab concentration and anti-natalizumab antibodies in multiple sclerosis","volume":"19","author":"Vennegoor","year":"2013","journal-title":"Mult Scler"},{"key":"B4","first-page":"489","volume-title":"Immunogenicity assessment of biosimilars: a multidisciplinary perspective","author":"Chamberlain","year":"2018"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1002\/cpt.1836","article-title":"The efficacy, safety, and immunogenicity of switching between reference biopharmaceuticals and biosimilars: a systematic review","volume":"108","author":"Barbier","year":"2020","journal-title":"Clin Pharmacol Ther"},{"key":"B6","unstructured":"Biosimilars in the EU. Information guide for healthcare professionals\n          \n          \n          \n          2019"},{"key":"B7","unstructured":"Scientific considerations in demonstrating biosimilarity to a reference product\n          \n          \n          \n          2015"},{"key":"B8","unstructured":"Clinical immunogenicity considerations for biosimilar and interchangeable insulin products\n          \n          \n          \n          2019"},{"key":"B9","unstructured":"Guideline on similar biological medicinal products containing biotechnology-derived proteins as active substance: non-clinical and clinical issues\n          \n          \n          \n          2014"},{"key":"B10","unstructured":"Immunogenicity testing of therapeutic protein products - developing and validating assays for anti-drug antibody detection\n          \n          \n          \n          2019"},{"key":"B11","unstructured":"Immunogenicity assessment for therapeutic protein products\n          \n          \n          \n          2014"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.4155\/bio-2021-0007","article-title":"2020 White paper on recent issues in bioanalysis: vaccine assay validation, qPCR assay validation, QC for CAR-T flow cytometry, NAb assay harmonization and ELISpot validation (part 3 - recommendations on immunogenicity assay strategies, NAb assays, biosim","volume":"13","author":"Corsaro","year":"2021","journal-title":"Bioanalysis"},{"key":"B13","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1208\/s12248-019-0386-y","article-title":"Recommendations for the development and validation of immunogenicity assays in support of biosimilar programs","volume":"22","author":"Civoli","year":"2020","journal-title":"AAPS J"},{"key":"B14","unstructured":"Hukyndra assessment report\n          \n          \n          \n          2021"},{"key":"B15","unstructured":"Imraldi assessment report\n          \n          \n          \n          2017"},{"key":"B16","unstructured":"FDA approves first biosimilar to treat multiple sclerosis\n          \n          \n          \n          2023"},{"key":"B17","unstructured":"Tyruko\u00ae (natalizumab)\n          \n          \n          \n          2023"},{"key":"B18","unstructured":"Tysabri\u00ae (natalizumab). Prescribing information\n          \n          \n          \n          2023"},{"key":"B19","unstructured":"Tysabri\u00ae (natalizumab). Summary of product characteristics\n          \n          \n          \n          2022"},{"key":"B20","unstructured":"Tysabri assessment report\n          \n          \n          \n          2021"},{"key":"B21","doi-asserted-by":"publisher","DOI":"10.1212\/01.wnl.0000277457.17420.b5","article-title":"The incidence and significance of anti-natalizumab antibodies: results from AFFIRM and SENTINEL","volume":"69","author":"Calabresi","year":"2007","journal-title":"Neurology"},{"key":"B22","doi-asserted-by":"publisher","first-page":"298","DOI":"10.1001\/JAMANEUROL.2022.5007","article-title":"Efficacy and safety of proposed biosimilar natalizumab (PB006) in patients with relapsing-remitting multiple sclerosis: the Antelope phase 3 randomized clinical trial","volume":"80","author":"Hemmer","year":"2023","journal-title":"JAMA Neurol"},{"key":"B23","doi-asserted-by":"publisher","DOI":"10.1080\/14712598.2023.2290530","article-title":"Pharmacokinetic and pharmacodynamic similarity of biosimilar natalizumab (PB006) to its reference medicine: a randomized controlled trial","volume":"23","author":"Wessels","year":"2023","journal-title":"Expert Opin Biol Ther"},{"key":"B24","unstructured":"Guideline on immunogenicity assessment of therapeutic proteins\n          \n          \n          \n          2017"},{"key":"B25","doi-asserted-by":"publisher","DOI":"10.1080\/07388551.2017.1416577","article-title":"Impact of host cell line choice on glycan profile","volume":"38","author":"Goh","year":"2018","journal-title":"Crit Rev Biotechnol"},{"key":"B26","doi-asserted-by":"publisher","DOI":"10.1007\/s40259-024-00671-4","article-title":"Introducing the biosimilar paradigm to neurology: the totality of evidence for the first biosimilar natalizumab","volume":"38","author":"Selmaj","year":"2024","journal-title":"BioDrugs"},{"key":"B27","doi-asserted-by":"publisher","DOI":"10.1002\/cpt.3033","article-title":"Investigation of immunogenicity assessment of biosimilar monoclonal antibodies in the United States","volume":"114","author":"Cheng","year":"2023","journal-title":"Clin Pharmacol Ther"},{"key":"B28","doi-asserted-by":"publisher","DOI":"10.1177\/1352458511404271","article-title":"Occurrence of antibodies against natalizumab in relapsing multiple sclerosis patients treated with natalizumab","volume":"17","author":"S\u00f8rensen","year":"2011","journal-title":"Mult Scler"},{"key":"B29","doi-asserted-by":"crossref","DOI":"10.1007\/978-0-387-75841-1_10","article-title":"Case study: immunogenicity of natalizumab","volume-title":"Immunogenicity of Biopharmaceuticals","author":"Subramanyam","year":"2008"},{"key":"B30","unstructured":"Tyruko\u00ae (natalizumab). Summary of product characteristics\n          \n          \n          \n          2023"},{"key":"B31","unstructured":"Tyruko\u00ae (Natalizumab-sztn). Prescribing information\n          \n          \n          \n          2023"}],"container-title":["Frontiers in Immunology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2024.1414304\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,12,19]],"date-time":"2024-12-19T01:24:47Z","timestamp":1734571487000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2024.1414304\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,12,19]]},"references-count":31,"alternative-id":["10.3389\/fimmu.2024.1414304"],"URL":"https:\/\/doi.org\/10.3389\/fimmu.2024.1414304","relation":{},"ISSN":["1664-3224"],"issn-type":[{"value":"1664-3224","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,12,19]]},"article-number":"1414304"}}