{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,19]],"date-time":"2026-09-19T02:35:55Z","timestamp":1789785355226,"version":"4.0.1"},"reference-count":31,"publisher":"Oxford University Press (OUP)","issue":"5","license":[{"start":{"date-parts":[[2025,5,22]],"date-time":"2025-05-22T00:00:00Z","timestamp":1747872000000},"content-version":"vor","delay-in-days":22,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Novo Nordisk A\/S"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2025,4,30]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>Somapacitan is a long-acting GH approved for once-weekly treatment of GH deficiency (GHD). This study aims to evaluate the efficacy and tolerability of somapacitan after 3 years of treatment and 2 years after switch from daily GH in children with GHD.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Design<\/jats:title>\n                    <jats:p>Randomized, multi-national, open-labelled, active-controlled parallel-group phase 3 trial, with a 52-week main phase and 3-year safety extension (NCT03811535).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Treatment-na\u00efve children with GHD were randomized (2:1) to continuous somapacitan (0.16\u2005mg\/kg\/week; \u201csoma\/soma\u201d group) or daily GH (Norditropin\u00ae; 0.034\u2005mg\/kg\/day) followed by somapacitan (0.16\u2005mg\/kg\/week; \u201cswitch\u201d group).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Of 200 participants, 188 completed 3 years of treatment. Sustained growth was observed in both groups. At week 156, mean (SD) height velocity (HV) between weeks 104 and 156 was 7.4 (1.5) cm\/year in the soma\/soma group and 7.8 (1.4) cm\/year in the switch group. At week 156, the soma\/soma and switch groups had reached a mean (SD) height SD score (HSDS) of \u22120.95 (0.98) and \u22121.08 (0.93), respectively, and were approaching the mean mid-parental HSDS of \u22120.74 (for both groups). Mean total insulin-like growth factor I (IGF-I) SDS during year 3 was similar between groups and within normal range (\u22122.0 to +2.0). Bioactive IGF-I and bioactive IGF-I to IGF-I ratio were similar between groups. Somapacitan was well tolerated, with low proportions reporting injection-site reactions.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Sustained efficacy and tolerability were observed for continuous somapacitan treatment for 3 years, and for 2 years after the switching from daily GH treatment. HSDS in both groups was approaching mean mid-parental HSDS.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Clinical trial registration<\/jats:title>\n                    <jats:p>NCT03811535<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1093\/ejendo\/lvaf096","type":"journal-article","created":{"date-parts":[[2025,5,15]],"date-time":"2025-05-15T07:52:23Z","timestamp":1747295543000},"page":"651-661","source":"Crossref","is-referenced-by-count":14,"title":["Efficacy, safety, and insulin-like growth factor I of weekly somapacitan in children with growth hormone deficiency: 3-year results from REAL4"],"prefix":"10.1093","volume":"192","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3663-5473","authenticated-orcid":false,"given":"Bradley S","family":"Miller","sequence":"first","affiliation":[{"name":"Division of Endocrinology, Department of Pediatrics, University of Minnesota Medical School, M Health Fairview Masonic Children's Hospital , Minneapolis, MN 55454 ,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3128-5574","authenticated-orcid":false,"given":"Joanne C","family":"Blair","sequence":"additional","affiliation":[{"name":"Department of Endocrinology, Alder Hey Children's NHS Foundation Trust , Liverpool L14 5AB ,","place":["United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2210-0366","authenticated-orcid":false,"given":"Michael H\u00f8jby","family":"Rasmussen","sequence":"additional","affiliation":[{"name":"Clinical Drug Development, Novo Nordisk A\/S , S\u00f8borg 2860 ,","place":["Denmark"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5379-0961","authenticated-orcid":false,"given":"Jan","family":"Frystyk","sequence":"additional","affiliation":[{"name":"Department of Clinical Research, Faculty of Health Sciences, University of Southern Denmark , Odense 5230 ,","place":["Denmark"]},{"name":"Department of Endocrinology, Odense University Hospital , Odense 5000 ,","place":["Denmark"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7929-7147","authenticated-orcid":false,"given":"Anders Krogh","family":"Lemminger","sequence":"additional","affiliation":[{"name":"Clinical Drug Development, Novo Nordisk A\/S , S\u00f8borg 2860 ,","place":["Denmark"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6705-8579","authenticated-orcid":false,"given":"Aristides","family":"Maniatis","sequence":"additional","affiliation":[{"name":"Rocky Mountain Pediatric Endocrinology , Centennial, CO 80112 ,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1271-1577","authenticated-orcid":false,"given":"Jun","family":"Mori","sequence":"additional","affiliation":[{"name":"Division of Pediatric Endocrinology, Metabolism and Nephrology, Children's Medical Center, Osaka City General Hospital, Osaka 534-0021 ,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Volker","family":"B\u00f6ttcher","sequence":"additional","affiliation":[{"name":"Division of Pediatric Endocrinology and Metabolism, MVZ Endokrinologikum Frankfurt am Main , Frankfurt 60596 ,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1135-099X","authenticated-orcid":false,"given":"Ho-Seong","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Severance Children's Hospital, Institute of Endocrinology, Yonsei University College of Medicine , Seoul 03722 ,","place":["Republic of Korea"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2639-352X","authenticated-orcid":false,"given":"Michel","family":"Polak","sequence":"additional","affiliation":[{"name":"Service d\u2019Endocrinologie, Gyn\u00e9cologie et Diab\u00e9tologie P\u00e9diatriques, H\u00f4pital Universitaire Necker Enfants Malades Paris, Universit\u00e9 Paris Cit\u00e9 Assistance Publique-H\u00f4pitaux de Paris , Paris 75015 ,","place":["France"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3429-3246","authenticated-orcid":false,"given":"Reiko","family":"Horikawa","sequence":"additional","affiliation":[{"name":"Division of Endocrinology and Metabolism, National Center for Child Health and Development , Tokyo 157-0074 ,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2025,5,22]]},"reference":[{"issue":"6","key":"2025052202302148800_lvaf096-B1","doi-asserted-by":"publisher","first-page":"361","DOI":"10.1159\/000452150","article-title":"Guidelines for growth hormone and insulin-like growth factor-I treatment in children and adolescents: growth hormone deficiency, idiopathic short stature, and primary insulin-like growth factor-I deficiency","volume":"86","author":"Grimberg","year":"2016","journal-title":"Horm Res Paediatr"},{"issue":"7","key":"2025052202302148800_lvaf096-B2","doi-asserted-by":"publisher","first-page":"1673","DOI":"10.1007\/s11136-017-1529-1","article-title":"Understanding burden of illness for child growth hormone deficiency","volume":"26","author":"Brod","year":"2017","journal-title":"Qual Life Res"},{"key":"2025052202302148800_lvaf096-B3","doi-asserted-by":"publisher","first-page":"101392","DOI":"10.1016\/j.ghir.2021.101392","article-title":"Impact of short stature on quality of life: a systematic literature review","volume":"57-58","author":"Backeljauw","year":"2021","journal-title":"Growth Horm IGF Res"},{"issue":"5","key":"2025052202302148800_lvaf096-B4","doi-asserted-by":"publisher","first-page":"421","DOI":"10.1530\/EJE-16-1024","article-title":"Early growth hormone treatment start in childhood growth hormone deficiency improves near adult height: analysis from NordiNet\u00ae International Outcome Study","volume":"177","author":"Polak","year":"2017","journal-title":"Eur J Endocrinol"},{"issue":"5","key":"2025052202302148800_lvaf096-B5","doi-asserted-by":"publisher","first-page":"653","DOI":"10.1007\/s40271-017-0237-9","article-title":"Understanding treatment burden for children treated for growth hormone deficiency","volume":"10","author":"Brod","year":"2017","journal-title":"Patient."},{"issue":"4","key":"2025052202302148800_lvaf096-B6","doi-asserted-by":"publisher","first-page":"267","DOI":"10.1097\/MED.0000000000000416","article-title":"The current state of long-acting growth hormone preparations for growth hormone therapy","volume":"25","author":"Yuen","year":"2018","journal-title":"Curr Opin Endocrinol Diabetes Obes"},{"key":"2025052202302148800_lvaf096-B7","doi-asserted-by":"publisher","first-page":"688","DOI":"10.3389\/fendo.2018.00688","article-title":"Shared decision-making in growth hormone therapy-implications for patient care","volume":"9","author":"Acerini","year":"2018","journal-title":"Front Endocrinol (Lausanne)"},{"issue":"6","key":"2025052202302148800_lvaf096-B8","doi-asserted-by":"publisher","first-page":"565","DOI":"10.1016\/j.eprac.2022.02.013","article-title":"Association of daily growth hormone injection adherence and height among children with growth hormone deficiency","volume":"28","author":"Loftus","year":"2022","journal-title":"Endocr Pract"},{"key":"2025052202302148800_lvaf096-B9","doi-asserted-by":"publisher","first-page":"980979","DOI":"10.3389\/fendo.2022.980979","article-title":"What do we do now that the long-acting growth hormone is here?","volume":"13","author":"Miller","year":"2022","journal-title":"Front Endocrinol (Lausanne)"},{"issue":"3","key":"2025052202302148800_lvaf096-B10","doi-asserted-by":"publisher","first-page":"988","DOI":"10.1210\/jc.2015-1991","article-title":"Reversible albumin-binding GH possesses a potential once-weekly treatment profile in adult growth hormone deficiency","volume":"101","author":"Rasmussen","year":"2016","journal-title":"J Clin Endocrinol Metab"},{"issue":"5","key":"2025052202302148800_lvaf096-B11","doi-asserted-by":"publisher","first-page":"491","DOI":"10.1530\/EJE-17-1073","article-title":"Safety and convenience of once-weekly somapacitan in adult GH deficiency: a 26-week randomized, controlled trial","volume":"178","author":"Johannsson","year":"2018","journal-title":"Eur J Endocrinol"},{"issue":"5","key":"2025052202302148800_lvaf096-B12","doi-asserted-by":"publisher","first-page":"620","DOI":"10.1111\/cen.14273","article-title":"Similar safety and efficacy in previously treated adults with growth hormone deficiency randomized to once-weekly somapacitan or daily growth hormone","volume":"93","author":"Otsuka","year":"2020","journal-title":"Clin Endocrinol (Oxf)"},{"issue":"4","key":"2025052202302148800_lvaf096-B13","doi-asserted-by":"publisher","first-page":"e1358","DOI":"10.1210\/clinem\/dgaa049","article-title":"Once-weekly somapacitan is effective and well tolerated in adults with GH deficiency: a randomized phase 3 trial","volume":"105","author":"Johannsson","year":"2020","journal-title":"J Clin Endocrinol Metab"},{"issue":"4","key":"2025052202302148800_lvaf096-B14","doi-asserted-by":"publisher","first-page":"350","DOI":"10.1111\/cen.13409","article-title":"Somapacitan, a once-weekly reversible albumin-binding GH derivative, in children with GH deficiency: a randomized dose-escalation trial","volume":"87","author":"Battelino","year":"2017","journal-title":"Clin Endocrinol (Oxf)"},{"issue":"4","key":"2025052202302148800_lvaf096-B15","doi-asserted-by":"publisher","first-page":"e1847","DOI":"10.1210\/clinem\/dgz310","article-title":"Once-weekly somapacitan vs daily GH in children with GH deficiency: results from a randomized phase 2 trial","volume":"105","author":"S\u00e4vendahl","year":"2020","journal-title":"J Clin Endocrinol Metab"},{"issue":"12","key":"2025052202302148800_lvaf096-B16","doi-asserted-by":"publisher","first-page":"3378","DOI":"10.1210\/clinem\/dgac513","article-title":"Weekly somapacitan is effective and well tolerated in children with GH deficiency: the randomized phase 3 REAL4 trial","volume":"107","author":"Miller","year":"2022","journal-title":"J Clin Endocrinol Metab"},{"issue":"12","key":"2025052202302148800_lvaf096-B17","doi-asserted-by":"publisher","first-page":"3090","DOI":"10.1210\/clinem\/dgad394","article-title":"Effective GH replacement with somapacitan in children with GHD: REAL4 2-year results and after switch from daily GH","volume":"108","author":"Miller","year":"2023","journal-title":"J Clin Endocrinol Metab"},{"issue":"5","key":"2025052202302148800_lvaf096-B18","doi-asserted-by":"publisher","first-page":"1357","DOI":"10.1210\/clinem\/dgab928","article-title":"Effective GH replacement with once-weekly somapacitan vs daily GH in children with GHD: 3-year results from REAL 3","volume":"107","author":"S\u00e4vendahl","year":"2022","journal-title":"J Clin Endocrinol Metab"},{"issue":"10","key":"2025052202302148800_lvaf096-B19","doi-asserted-by":"publisher","first-page":"2569","DOI":"10.1210\/clinem\/dgad183","article-title":"Weekly somapacitan in GH deficiency: 4-year efficacy, safety and treatment\/disease burden results from REAL 3","volume":"108","author":"S\u00e4vendahl","year":"2023","journal-title":"J Clin Endocrinol Metab"},{"issue":"26","key":"2025052202302148800_lvaf096-B20","doi-asserted-by":"publisher","first-page":"2551","DOI":"10.1056\/NEJMra1817346","article-title":"Pathogenesis and diagnosis of growth hormone deficiency in adults","volume":"380","author":"Melmed","year":"2019","journal-title":"N Engl J Med"},{"issue":"5","key":"2025052202302148800_lvaf096-B21","doi-asserted-by":"publisher","first-page":"337","DOI":"10.1016\/j.ghir.2004.06.001","article-title":"Free insulin-like growth factors\u2014measurements and relationships to growth hormone secretion and glucose homeostasis","volume":"14","author":"Frystyk","year":"2004","journal-title":"Growth Horm IGF Res"},{"issue":"4","key":"2025052202302148800_lvaf096-B22","doi-asserted-by":"publisher","first-page":"986","DOI":"10.1210\/clinem\/dgac609","article-title":"Serum IGF-1 to IGFBP-3 molar ratio: a promising diagnostic tool for growth hormone deficiency in children","volume":"108","author":"Haj-Ahmad","year":"2023","journal-title":"J Clin Endocrinol Metab"},{"issue":"1","key":"2025052202302148800_lvaf096-B23","doi-asserted-by":"publisher","first-page":"80","DOI":"10.1186\/1471-2369-14-80","article-title":"Effect of hyperinsulinemia during hemodialysis on the insulin-like growth factor system and inflammatory biomarkers: a randomized open-label crossover study","volume":"14","author":"Reinhard","year":"2013","journal-title":"BMC Nephrol"},{"issue":"6","key":"2025052202302148800_lvaf096-B24","doi-asserted-by":"publisher","first-page":"E1149","DOI":"10.1152\/ajpendo.00410.2002","article-title":"A highly sensitive and specific assay for determination of IGF-I bioactivity in human serum","volume":"284","author":"Chen","year":"2003","journal-title":"Am J Physiol Endocrinol Metab"},{"key":"2025052202302148800_lvaf096-B25","volume-title":"Guideline for Good Clinical Practice E6","author":"ICH Harmonised Tripartite Guideline","year":"2016"},{"issue":"5","key":"2025052202302148800_lvaf096-B26","doi-asserted-by":"publisher","first-page":"1675","DOI":"10.1210\/jc.2013-3060","article-title":"Age- and sex-specific reference intervals across life span for insulin-like growth factor binding protein 3 (IGFBP-3) and the IGF-I to IGFBP-3 ratio measured by new automated chemiluminescence assays","volume":"99","author":"Friedrich","year":"2014","journal-title":"J Clin Endocrinol Metab"},{"issue":"5","key":"2025052202302148800_lvaf096-B27","doi-asserted-by":"publisher","first-page":"1214","DOI":"10.1210\/clinem\/dgad717","article-title":"Gene expression signatures predict first-year response to somapacitan treatment in children with GH deficiency","volume":"109","author":"Garner","year":"2024","journal-title":"J Clin Endocrinol Metab"},{"issue":"3","key":"2025052202302148800_lvaf096-B28","doi-asserted-by":"publisher","first-page":"253","DOI":"10.4274\/jcrpe.galenos.2019.2018.0277","article-title":"Evaluation of IGF1\/IGFBP3 molar ratio as an effective tool for assessing the safety of growth hormone therapy in small-for-gestational-age, growth hormone-deficient and Prader-Willi children","volume":"11","author":"Gaddas","year":"2019","journal-title":"J Clin Res Pediatr Endocrinol"},{"issue":"4","key":"2025052202302148800_lvaf096-B29","doi-asserted-by":"publisher","first-page":"1086","DOI":"10.1210\/clinem\/dgae616","article-title":"Somapacitan in children born SGA: 52-week efficacy, safety, and IGF-I response results from the phase 2 REAL5 study","volume":"110","author":"Juul","year":"2025","journal-title":"J Clin Endocrinol Metab"},{"issue":"4","key":"2025052202302148800_lvaf096-B30","doi-asserted-by":"publisher","first-page":"dgz118","DOI":"10.1210\/clinem\/dgz118","article-title":"Increases in bioactive IGF do not parallel increases in total IGF-I during growth hormone treatment of children born SGA","volume":"105","author":"Wegmann","year":"2020","journal-title":"J Clin Endocrinol Metab"},{"key":"2025052202302148800_lvaf096-B31","unstructured":"Miller BS, Blair JC, Rasmussen MH, et al \u00a02025. Plain language summary for \u201cEfficacy, safety, and insulin-like growth factor I of weekly somapacitan in children with growth hormone deficiency: 3-year results from REAL4\u201d. figshare. Journal contribution. 10.6084\/m9.figshare.28920029"}],"container-title":["European Journal of Endocrinology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/ejendo\/article-pdf\/192\/5\/651\/63268961\/lvaf096.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/ejendo\/article-pdf\/192\/5\/651\/63268961\/lvaf096.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,5,22]],"date-time":"2025-05-22T02:30:29Z","timestamp":1747881029000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/ejendo\/article\/192\/5\/651\/8140353"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,4,30]]},"references-count":31,"journal-issue":{"issue":"5","published-print":{"date-parts":[[2025,4,30]]}},"URL":"https:\/\/doi.org\/10.1093\/ejendo\/lvaf096","relation":{},"ISSN":["0804-4643","1479-683X"],"issn-type":[{"value":"0804-4643","type":"print"},{"value":"1479-683X","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2025,5]]},"published":{"date-parts":[[2025,4,30]]}}}