{"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":1788459884956,"version":"build-2803163510"},"reference-count":48,"publisher":"Wiley","issue":"12","license":[{"start":{"date-parts":[[2025,11,30]],"date-time":"2025-11-30T00:00:00Z","timestamp":1764460800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000038","name":"U.S. Food and Drug Administration","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000038","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["ascpt.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Clinical Translational Sci"],"published-print":{"date-parts":[[2025,12]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Proteomics can identify pharmacodynamic (PD) biomarkers by detecting protein changes in response to drug treatment, providing insights into drug mechanism and biological effects. In this study, we profiled over 7000 plasma proteins to identify potential PD biomarkers for the interleukin\u20105 (IL\u20105) inhibitors mepolizumab and reslizumab, which are approved for treating eosinophilic asthma. We used longitudinal plasma samples from healthy participants treated with a single dose of mepolizumab (\n                    <jats:italic>n<\/jats:italic>\n                    \u2009=\u20098, 24\u2009mg) or reslizumab (\n                    <jats:italic>n<\/jats:italic>\n                    \u2009=\u20098, 0.8\u2009mg\/kg), or placebo (\n                    <jats:italic>n<\/jats:italic>\n                    \u2009=\u20098) to identify differentially expressed proteins. We then characterized PD biomarker candidates by their magnitude of response, area under the effect curve (AUEC), dose\u2013response, variability, and replication of response at a lower dose for mepolizumab (\n                    <jats:italic>n<\/jats:italic>\n                    \u2009=\u20098, 12\u2009mg) or reslizumab (\n                    <jats:italic>n<\/jats:italic>\n                    \u2009=\u20098, 0.4\u2009mg\/kg) compared to placebo. Eosinophil major basic protein (EMBP) and proteoglycan\u20103 (PRG3) were differentially expressed in response to mepolizumab and reslizumab, respectively, achieving Bonferroni\u2010adjusted statistical significance (\n                    <jats:italic>p<\/jats:italic>\n                    \u2010value\u2009&lt;\u20096.86E\u201006) and nominal significance (\n                    <jats:italic>p<\/jats:italic>\n                    \u2010value\u2009&lt;\u20095.0E\u201005) with the other IL\u20105 inhibitor. EMBP showed a &gt;\u200920% fold change difference with mepolizumab (24\u2009mg) versus placebo at peak time, and PRG3 demonstrated a &gt;\u200920% fold change with reslizumab (0.8\u2009mg\/kg) versus placebo at peak time. Both proteins had significant AUEC with both drug doses, with EMBP AUEC only significant (absolute AUEC high\u2009&gt;\u2009low dose) at the higher mepolizumab dose. Both biomarkers showed dose\u2013response trends and comparable variability to placebo. Our study identified EMBP and PRG3 as promising plasma PD biomarkers for IL\u20105 inhibitors, warranting further validation for early phase trials and biosimilar development programs.\n                  <\/jats:p>","DOI":"10.1111\/cts.70412","type":"journal-article","created":{"date-parts":[[2025,11,30]],"date-time":"2025-11-30T15:06:08Z","timestamp":1764515168000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Proteomic Identification of Plasma Biomarkers of Response to IL\u20105 Inhibitor Biologics in Healthy Subjects"],"prefix":"10.1111","volume":"18","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 and Drug Administration  Silver Spring Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6647-8558","authenticated-orcid":false,"given":"Deepti P.","family":"Samarth","sequence":"additional","affiliation":[{"name":"Division of Applied Regulatory Science, 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"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8891-754X","authenticated-orcid":false,"given":"Kristina E.","family":"Howard","sequence":"additional","affiliation":[{"name":"Division of Applied Regulatory Science, 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":"Yan","family":"Guo","sequence":"additional","affiliation":[{"name":"Division of Applied Regulatory Science, 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":"Esraa G.","family":"Mohamed","sequence":"additional","affiliation":[{"name":"Division of Applied Regulatory Science, 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":"Erica","family":"Decker","sequence":"additional","affiliation":[{"name":"Division of Applied Regulatory Science, 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":"Joel","family":"Wommack","sequence":"additional","affiliation":[{"name":"Standard BioTools, Inc.  Boulder Colorado USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joseph","family":"Gogain","sequence":"additional","affiliation":[{"name":"Standard BioTools, Inc.  Boulder Colorado USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jennifer","family":"Deering","sequence":"additional","affiliation":[{"name":"Spaulding Clinical Research  West Bend Wisconsin USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sarah J.","family":"Schrieber","sequence":"additional","affiliation":[{"name":"Office of Therapeutic Biologics and Biosimilars, Office of New Drugs, Center for Drug Evaluation and Research U.S. Food and Drug Administration  Silver Spring Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0663-7358","authenticated-orcid":false,"given":"Yow\u2010Ming","family":"Wang","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":"David G.","family":"Strauss","sequence":"additional","affiliation":[{"name":"Division of Applied Regulatory Science, 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"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-1984-8026","authenticated-orcid":false,"given":"Jeffry","family":"Florian","sequence":"additional","affiliation":[{"name":"Division of Applied Regulatory Science, 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"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0516-3389","authenticated-orcid":false,"given":"Paula L.","family":"Hyland","sequence":"additional","affiliation":[{"name":"Division of Applied Regulatory Science, 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"}]}],"member":"311","published-online":{"date-parts":[[2025,11,30]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1002\/cpt.2778"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1093\/intimm\/dxp102"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1111\/all.15056"},{"key":"e_1_2_9_5_1","volume-title":"BEST (Biomarkers, EndpointS, and Other Tools) Resource [Internet]","author":"FDA\u2010NIH Biomarker Working Group","year":"2016"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1097\/BOR.0000000000000250"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaip.2020.08.039"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.2147\/DDDT.S150656"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1002\/cpt.2760"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1111\/all.15751"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaip.2020.10.033"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.alit.2022.11.008"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaip.2021.02.053"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.3109\/02770901003792833"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ebiom.2023.104936"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms25063501"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.3390\/jpm10040164"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-017-14755-5"},{"key":"e_1_2_9_19_1","volume-title":"FDA Guidance: Scientific Considerations in Demonstrating Biosimilarity to a Reference Product","author":"US Food and Drug Administration","year":"2015"},{"key":"e_1_2_9_20_1","volume-title":"FDA Guidance: Clinical Pharmacology Data to Support a Demonstration of Biosimilarity to a Reference Product","author":"US Food and Drug Administration","year":"2016"},{"key":"e_1_2_9_21_1","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btt703"},{"key":"e_1_2_9_22_1","doi-asserted-by":"publisher","DOI":"10.1111\/all.15089"},{"key":"e_1_2_9_23_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12931-022-01968-0"},{"key":"e_1_2_9_24_1","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-13-3132"},{"key":"e_1_2_9_25_1","volume-title":"Phase I Oncology Drug Development","author":"Mar\u00eda Vieito I. 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