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To support a pediatric indication (\u22656 years), an extrapolation approach was implemented. This extrapolation and its validation were informed by data from Phase III trials in adults (N = 1841) and adolescents aged 12\u201017 years (N = 37) with severe asthma, an open\u2010label trial in children aged 6\u201011 years (N = 36), and a trial in children aged 2\u201011 years (N = 32) and adolescents aged 12\u201017 years (N = 27) with eosinophilic esophagitis. Population pharmacokinetic and pharmacokinetic\/pharmacodynamic meta\u2010analyses demonstrated consistent mepolizumab pharmacokinetic and blood eosinophil reduction across age groups and diseases, with bodyweight the only covariate of exposure and absolute bioavailability also a covariate in children aged 6\u201011 years. Baseline blood eosinophil count and disease type were the only covariates of response. 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This extrapolation strategy, implemented as an innovative approach to pediatric clinical development of mepolizumab in severe asthma, was validated and provided the scientific basis for dosing recommendations and for EU regulatory approval in patients aged \u22656 years in 2018.<\/jats:p>","DOI":"10.1002\/jcph.70155","type":"journal-article","created":{"date-parts":[[2026,2,16]],"date-time":"2026-02-16T08:31:12Z","timestamp":1771230672000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Development of Pediatric Dosing for Mepolizumab in Severe Asthma Based on Extrapolation of Data From Adult Patients and a Phase II Open\u2010Label Pediatric Trial"],"prefix":"10.1002","volume":"66","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1610-0335","authenticated-orcid":false,"given":"Atul","family":"Gupta","sequence":"first","affiliation":[{"name":"Paediatric Respiratory Department, King's College Hospital Department of Women and Children's Health  London UK"},{"name":"Faculty of Life Sciences and Medicine King's College London  London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Isabelle J.","family":"Pouliquen","sequence":"additional","affiliation":[{"name":"Research &amp; Development GSK  London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8639-0473","authenticated-orcid":false,"given":"Wanda","family":"Phipatanakul","sequence":"additional","affiliation":[{"name":"Division of Allergy and Immunology, Department of Pediatrics, Boston Children's Hospital Harvard Medical School  Boston MA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daren","family":"Austin","sequence":"additional","affiliation":[{"name":"Research &amp; Development GSK  London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Glenn","family":"Whelan","sequence":"additional","affiliation":[{"name":"Respiratory Biologics GSK  Ponte Vedra Beach FL USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6418-6818","authenticated-orcid":false,"given":"Robert G.","family":"Price","sequence":"additional","affiliation":[{"name":"Biostatistics GSK  Stevenage Hertfordshire UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tricia","family":"Finney\u2010Hayward","sequence":"additional","affiliation":[{"name":"Global Medical Affairs GSK  London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sabine","family":"Derey","sequence":"additional","affiliation":[{"name":"Global Regulatory Affairs GSK  Rueil\u2010Malmaison France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jonathan","family":"Steinfeld","sequence":"additional","affiliation":[{"name":"Research &amp; Development GSK  Collegeville PA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,2,16]]},"reference":[{"key":"e_1_2_13_2_1","doi-asserted-by":"publisher","DOI":"10.1002\/JLB.1MR1117-442RR"},{"key":"e_1_2_13_3_1","doi-asserted-by":"publisher","DOI":"10.1111\/all.15627"},{"key":"e_1_2_13_4_1","doi-asserted-by":"publisher","DOI":"10.1111\/all.14297"},{"key":"e_1_2_13_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.anai.2023.01.024"},{"key":"e_1_2_13_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaci.2020.02.035"},{"key":"e_1_2_13_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaci.2021.05.043"},{"key":"e_1_2_13_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaip.2022.09.008"},{"key":"e_1_2_13_9_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI95693"},{"key":"e_1_2_13_10_1","doi-asserted-by":"publisher","DOI":"10.1002\/alr.22994"},{"key":"e_1_2_13_11_1","doi-asserted-by":"publisher","DOI":"10.1111\/resp.14506"},{"key":"e_1_2_13_12_1","doi-asserted-by":"publisher","DOI":"10.3389\/fphys.2019.01514"},{"key":"e_1_2_13_13_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1403290"},{"key":"e_1_2_13_14_1","doi-asserted-by":"publisher","DOI":"10.1183\/13993003.01874-2019"},{"key":"e_1_2_13_15_1","unstructured":"EMA.Nucala summary of product characteristics. 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