{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,3]],"date-time":"2026-09-03T18:24:44Z","timestamp":1788459884543,"version":"build-2803163510"},"reference-count":30,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2025,7,4]],"date-time":"2025-07-04T00:00:00Z","timestamp":1751587200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["ascpt.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Clin Pharma and Therapeutics"],"published-print":{"date-parts":[[2025,10]]},"abstract":"<jats:p>Pharmacodynamic (PD) biomarkers can support biosimilarity assessment, potentially reducing the need for comparative clinical efficacy studies. This study aimed to characterize previously identified proteomic PD biomarker candidates for Interferon beta\u20101a (IFN\u03b2\u20101a, <jats:italic>n<\/jats:italic>\u2009=\u2009248) and pegylated IFN\u03b2\u20101a (pegIFN\u03b2\u20101a, <jats:italic>n<\/jats:italic>\u2009=\u2009528) biologics at therapeutic doses, to further evaluate the utility of proteomics in biosimilar development. Here, we reproduced the results at lower doses and characterized PD responses across multiple doses using criteria for justifying PD biomarker use in biosimilar development. We analyzed candidate proteins from longitudinal proteomics data (SomaScan\u2122 Assay v4.1) from 48 healthy subjects administered intermediate or low doses of IFN\u03b2\u20101a (15, 7.5\u2009\u03bcg) or pegIFN\u03b2\u20101a (62.5, 31.25\u2009\u03bcg) in an FDA\u2010sponsored study, alongside previously published therapeutic dose and placebo data. EDTA plasma samples were collected at 0, 0.125, 0.33, 0.67, 1.33, 2, 3, 4, 5, 6\u2009days and at 9, 13\u2009days additionally for pegIFN\u03b2\u20101a. Prioritization criteria included significant differential expression at the intermediate dose vs. placebo, \u226520% response difference from placebo, significant baseline\u2010adjusted area under the effect curve (AUEC) and a monotonic dose\u2013response relationship across all doses. Among the candidates, 165 and 323 were differentially expressed at intermediate doses of IFN\u03b2\u20101a and pegIFN\u03b2\u20101a respectively. Nine PD biomarkers, including C\u2010X\u2010C motif chemokine 11 (I\u2010TAC), Lymphocyte activation gene 3 protein (LAG3), and Granulins (GRN), were prioritized as common to both biologics. Most candidates followed the <jats:italic>E<\/jats:italic><jats:sub>max<\/jats:sub> dose\u2013response model. I\u2010TAC showed the strongest response, and LAG\u20103 showed the least variability in AUEC. Our study identified several suitable plasma PD biomarkers for IFN\u03b2\u20101a and pegIFN\u03b2\u20101a biologics with potential utility in biosimilar development programs.<\/jats:p>","DOI":"10.1002\/cpt.3754","type":"journal-article","created":{"date-parts":[[2025,7,4]],"date-time":"2025-07-04T09:45:59Z","timestamp":1751622359000},"page":"935-945","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Characterization of Proteomic Pharmacodynamic Biomarkers of <scp>IFN\u03b2<\/scp>\u20101a Biologics to Inform Potential Utility in Biosimilar Development"],"prefix":"10.1002","volume":"118","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5996-9180","authenticated-orcid":false,"given":"Lakshmi Manasa S.","family":"Chekka","sequence":"first","affiliation":[{"name":"Division of Applied Regulatory Science Office of Clinical Pharmacology, Office of Translational Sciences, Center for Drug Evaluation and Research, U.S. Food 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USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7499-2055","authenticated-orcid":false,"given":"Qin","family":"Sun","sequence":"additional","affiliation":[{"name":"Therapeutic Biologics Program Office of Clinical Pharmacology, Office of Translational Sciences, Center for Drug Evaluation and Research, U.S. Food and Drug Administration  Silver Spring Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"William","family":"Wheeler","sequence":"additional","affiliation":[{"name":"Information Management Services, Inc  Rockville Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carlos","family":"Sanabria","sequence":"additional","affiliation":[{"name":"Spaulding Clinical Research  West Bend Wisconsin USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joel","family":"Wommack","sequence":"additional","affiliation":[{"name":"Standard BioTools, Inc  Boulder Colorado 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