{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,10]],"date-time":"2026-10-10T18:33:14Z","timestamp":1791657194759,"version":"4.3.4"},"reference-count":29,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2026,1,15]],"date-time":"2026-01-15T00:00:00Z","timestamp":1768435200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"},{"start":{"date-parts":[[2026,1,15]],"date-time":"2026-01-15T00:00:00Z","timestamp":1768435200000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100009754","name":"Galderma","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100009754","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Br J Clin Pharmacol"],"published-print":{"date-parts":[[2026,6]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Aims<\/jats:title>\n                    <jats:p>Population pharmacokinetic (popPK) and pharmacokinetic\u2010pharmacodynamic (PK\/PD) models were developed to support clinical development of nemolizumab, a humanized monoclonal antibody targeting the IL\u201031 receptor \u03b1, in adolescents and adults with moderate\u2010to\u2010severe atopic dermatitis (AD).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Starting from previous analyses, data from phase 2 to phase 3 studies in AD and prurigo nodularis were integrated into popPK model development. In initial PK\/PD model development, a turnover model was used for Eczema Area and Severity Index (EASI) and Peak Pruritus Numerical Rating Scale (PP NRS) endpoints, while a continuous\u2010time Markov model was used for Investigator's Global Assessment (IGA) scores. A model\u2010informed drug development (MIDD) approach based on popPK and PK\/PD modelling and simulations was applied to support dose selection in patients with AD.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Nemolizumab exposures decreased with increasing bodyweight. The popPK simulation predicted different median Ctroughs according to bodyweight &lt;90\u2009kg or \u226590\u2009kg: 2.51\n                      <jats:italic>vs<\/jats:italic>\n                      . 1.71\u2009\u03bcg\/mL, respectively. However, PK\/PD simulations showed that the proportion of responders for EASI, PP NRS and IGA endpoints was similar in both groups: 37.5%, 55.6% and 31.6%\n                      <jats:italic>vs<\/jats:italic>\n                      . 35.1%, 53.4% and 26.3% for bodyweight &lt;90\u2009kg or \u226590\u2009kg, respectively. Reduced response of IGA to nemolizumab treatment was identified for male subjects (23.4%\n                      <jats:italic>vs<\/jats:italic>\n                      . 34.0%) and severe baseline score (19.3%\n                      <jats:italic>vs<\/jats:italic>\n                      . 32.3%) with consistent trends between bodyweight group.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>The overall MIDD approach supported the nemolizumab program by confirming the recommended dosing regimen of 30\u2009mg every four weeks with a 60\u2009mg loading dose in all patients with AD.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/bcp.70435","type":"journal-article","created":{"date-parts":[[2026,1,15]],"date-time":"2026-01-15T23:50:54Z","timestamp":1768521054000},"page":"1744-1759","source":"Crossref","is-referenced-by-count":1,"title":["Model\u2010informed drug development to support nemolizumab clinical development in adults and adolescents with moderate to severe atopic dermatitis"],"prefix":"10.1002","volume":"92","author":[{"given":"Floris","family":"Fauchet","sequence":"first","affiliation":[{"name":"Certara USA, Inc.  Radnor PA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna","family":"Largajolli","sequence":"additional","affiliation":[{"name":"Certara USA, Inc.  Radnor PA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Petra M.","family":"Jauslin","sequence":"additional","affiliation":[{"name":"Certara USA, Inc.  Radnor PA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emilie","family":"Schindler","sequence":"additional","affiliation":[{"name":"Roche Pharma Research and Early Development, Pharmaceutical Sciences, Roche Innovation Center Basel  Basel Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mourad","family":"Hamimed","sequence":"additional","affiliation":[{"name":"Certara USA, Inc.  Radnor PA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wannee","family":"Kantasiripitak","sequence":"additional","affiliation":[{"name":"Certara USA, Inc.  Radnor PA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antonio","family":"Gon\u00e7alves","sequence":"additional","affiliation":[{"name":"Certara USA, Inc.  Radnor PA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eline","family":"Van Maanen","sequence":"additional","affiliation":[{"name":"Certara USA, Inc.  Radnor PA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Khaled","family":"Benkali","sequence":"additional","affiliation":[{"name":"Certara USA, Inc.  Radnor PA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tomohisa","family":"Saito","sequence":"additional","affiliation":[{"name":"Chugai Pharmaceutical Co., Ltd  Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jonathan I.","family":"Silverberg","sequence":"additional","affiliation":[{"name":"Department of Dermatology The George Washington University School of Medicine and Health Sciences  Washington DC USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andreas","family":"Wollenberg","sequence":"additional","affiliation":[{"name":"Department of Dermatology and Allergology Ludwig\u2010Maximilians\u2010Universit\u00e4t  Munich Germany"},{"name":"Vrije Universiteit Brussel, Universitair Ziekenhuis Brussel, Department of Dermatology  Brussels Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Graeber","sequence":"additional","affiliation":[{"name":"Galderma R&amp;D  Fort Worth Texas USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liliana","family":"Ulianov","sequence":"additional","affiliation":[{"name":"Galderma R&amp;D  Lausanne Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christophe","family":"Piketty","sequence":"additional","affiliation":[{"name":"Galderma R&amp;D  Zug Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luca","family":"Loprete","sequence":"additional","affiliation":[{"name":"Galderma R&amp;D  Zug Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vincent","family":"Duval","sequence":"additional","affiliation":[{"name":"Certara USA, Inc.  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