{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,22]],"date-time":"2026-10-22T19:57:58Z","timestamp":1792699078225,"version":"4.5.0"},"reference-count":16,"publisher":"Oxford University Press (OUP)","issue":"2","license":[{"start":{"date-parts":[[2018,9,14]],"date-time":"2018-09-14T00:00:00Z","timestamp":1536883200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004095","name":"Kyowa Hakko Kirin","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100004095","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["asbmr.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["JBMR Plus"],"published-print":{"date-parts":[[2019,2]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:sec><jats:label\/><jats:p>X\u2010linked hypophosphatemia (XLH) is a disease caused by abnormally elevated FGF23 levels, which cause persistent hypophosphatemia accompanied by subsequent reduction in bone mineralization that presents as rickets or osteomalacia. Burosumab is a fully human monoclonal antibody targeting FGF23 that is under development for the treatment of FGF23\u2010related hypophosphatemia including XLH. The safety, tolerability, and proof of concept of burosumab have been evaluated in patients with XLH in previous studies conducted in countries outside of Asia. The objective of this study was to evaluate the safety, tolerability, pharmacokinetics (PK), pharmacodynamics (PD), and expression of anti\u2010drug antibodies in Japanese and Korean adults with XLH. This was a multicenter, sequential dose\u2010escalation, open\u2010label, single\u2010dose study. This study began with cohort 1 (s.c. dose of burosumab 0.3\u2009mg\/kg), after which the dose was escalated sequentially in cohort 2 (s.c. dose of burosumab 0.6\u2009mg\/kg) and cohort 3 (s.c. dose of burosumab 1.0\u2009mg\/kg). The PK of burosumab were linear within the dose range of 0.3 to 1.0\u2009mg\/kg. The PD effects such as serum phosphorus concentration, serum 1,25[OH]<jats:sub>2<\/jats:sub>D<jats:sub>3<\/jats:sub> concentration, and ratio of tubular maximum reabsorption rate of phosphate to glomerular filtration rate (TmP\/GFR) were elevated after a single s.c. administration. The area under the receiver\u2010operating characteristic curve from 0 to <jats:italic>t<\/jats:italic> (AUC<jats:sub>0\u2013t<\/jats:sub>) values calculated using the change from baseline values of serum phosphorus, serum 1,25(OH)<jats:sub>2<\/jats:sub>D<jats:sub>3<\/jats:sub>, and TmP\/GFR were correlated with the AUC<jats:sub>0\u2013t<\/jats:sub> of burosumab. Furthermore, no serious adverse events (AEs), deaths, remarkable increase or decrease in the corrected calcium or intact PTH levels, or signs of nephrocalcinosis or its worsening were observed after treatment. Some AEs and drug\u2010related AEs were observed; however, there were no clinically meaningful tendencies. The positive effects and acceptable safety profile seen in this study are encouraging for Japanese and Korean patients with XLH. \u00a9 2018 The Authors <jats:italic>JBMR Plus<\/jats:italic> published by Wiley Periodicals, Inc. on behalf of American Society for Bone and Mineral Research.<\/jats:p><\/jats:sec>","DOI":"10.1002\/jbm4.10074","type":"journal-article","created":{"date-parts":[[2018,9,16]],"date-time":"2018-09-16T09:50:09Z","timestamp":1537091409000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["First\u2010in\u2010Asian Phase I Study of the Anti\u2010Fibroblast Growth Factor 23 Monoclonal Antibody, Burosumab: Safety and Pharmacodynamics in Adults With X\u2010linked Hypophosphatemia"],"prefix":"10.1093","volume":"3","author":[{"given":"Hae Il","family":"Cheong","sequence":"first","affiliation":[{"name":"Department of Pediatrics Seoul National University  Children's  Hospital Seoul Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Han\u2010Wook","family":"Yoo","sequence":"additional","affiliation":[{"name":"Department of Pediatrics Asan Medical Center Seoul Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masanori","family":"Adachi","sequence":"additional","affiliation":[{"name":"Department of Endocrinology and Metabolism Kanagawa Children's Medical Center Kanagawa Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hiroyuki","family":"Tanaka","sequence":"additional","affiliation":[{"name":"Department of Pediatrics Okayama Saiseikai General Hospital Okayama Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ikuma","family":"Fujiwara","sequence":"additional","affiliation":[{"name":"Department of Pediatric Endocrinology and Environmental Medicine Tohoku University Graduate School of Medicine Miyagi Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yukihiro","family":"Hasegawa","sequence":"additional","affiliation":[{"name":"Division of Endocrinology and Metabolism Tokyo Metropolitan Children's Medical Center Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daisuke","family":"Harada","sequence":"additional","affiliation":[{"name":"Department of Pediatrics Osaka Hospital Japan Community Healthcare Organization (JCHO) Osaka Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maiko","family":"Sugimoto","sequence":"additional","affiliation":[{"name":"Kyowa Hakko Kirin Co. Ltd Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yosuke","family":"Okada","sequence":"additional","affiliation":[{"name":"Kyowa Hakko Kirin Co. Ltd Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masaki","family":"Kato","sequence":"additional","affiliation":[{"name":"Kyowa Hakko Kirin Co. Ltd Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ryutaro","family":"Shimazaki","sequence":"additional","affiliation":[{"name":"Kyowa Hakko Kirin Co. Ltd Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Keiichi","family":"Ozono","sequence":"additional","affiliation":[{"name":"Department of Pediatrics Osaka University Graduate School of Medicine Osaka Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yoshiki","family":"Seino","sequence":"additional","affiliation":[{"name":"Department of Pediatrics Osaka Hospital Japan Community Healthcare Organization (JCHO) Osaka Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2018,9,14]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1002\/jbmr.340"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajprenal.90742.2008"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1681\/ASN.2005050573"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1681\/ASN.2007010068"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1359\/JBMR.0301264"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2006-0021"},{"issue":"10","key":"e_1_2_7_8_1","first-page":"1592","article-title":"[Hypophosphatemic rickets\/osteomalacia. Mainly on patients with PHEX mutations]","volume":"17","author":"Hasegawa Y","year":"2007","journal-title":"Clin Calcium"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.1097\/00005792-198911000-00002"},{"issue":"2","key":"e_1_2_7_10_1","first-page":"367","article-title":"The changing face of hypophosphatemic disorders in the FGF\u201023 era","author":"Lee JY","year":"2013","journal-title":"Pediatr Endocrinol Rev"},{"key":"e_1_2_7_11_1","doi-asserted-by":"publisher","DOI":"10.1530\/EC-13-0103"},{"issue":"6","key":"e_1_2_7_12_1","first-page":"852","article-title":"Treatment of hypophosphatemia","volume":"19","author":"Minagawa M.","year":"2009","journal-title":"Clin Calcium"},{"key":"e_1_2_7_13_1","doi-asserted-by":"publisher","DOI":"10.1210\/jcem-52-3-463"},{"issue":"2","key":"e_1_2_7_14_1","first-page":"269","article-title":"FGF23 related hypophosphatemic rickets: current therapy and unresolved issue","volume":"26","author":"Harada D","year":"2016","journal-title":"Clin Calcium"},{"key":"e_1_2_7_15_1","doi-asserted-by":"publisher","DOI":"10.1359\/jbmr.080417"},{"key":"e_1_2_7_16_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI72829"},{"key":"e_1_2_7_17_1","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2015-1551"}],"container-title":["JBMR Plus"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fjbm4.10074","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/onlinelibrary.wiley.com\/wol1\/doi\/10.1002\/jbm4.10074\/fullpdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,3,14]],"date-time":"2024-03-14T13:54:01Z","timestamp":1710424441000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/jbmrplus\/article\/3\/2\/n\/a\/7478863"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2018,9,14]]},"references-count":16,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2019,2]]}},"alternative-id":["10.1002\/jbm4.10074"],"URL":"https:\/\/doi.org\/10.1002\/jbm4.10074","archive":["Portico"],"relation":{},"ISSN":["2473-4039","2473-4039"],"issn-type":[{"value":"2473-4039","type":"print"},{"value":"2473-4039","type":"electronic"}],"subject":[],"published":{"date-parts":[[2018,9,14]]},"assertion":[{"value":"2018-05-31","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2018-08-05","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2018-09-14","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e10074"}}