{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,29]],"date-time":"2026-10-29T08:27:49Z","timestamp":1793262469610,"version":"4.5.0"},"reference-count":43,"publisher":"Oxford University Press (OUP)","issue":"6","license":[{"start":{"date-parts":[[2026,5,18]],"date-time":"2026-05-18T00:00:00Z","timestamp":1779062400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100030826","name":"Ascendis Pharma, Inc.","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100030826","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,6,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>Navepegritide, a prodrug of C-type natriuretic peptide, has demonstrated improved growth and additional benefits, including lower limb alignment, in children with achondroplasia. The well-described mechanism of action of navepegritide in the growth plate is hypothesized to enhance its receptivity to lonapegsomatropin, a prodrug of somatropin, to provide benefits beyond those seen with monotherapies in achondroplasia.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>In the proof-of-concept phase 2 COACH trial, children with achondroplasia aged 2 to 11 received weekly navepegritide and lonapegsomatropin. The primary efficacy endpoint was annualized growth velocity (AGV) at week 52 vs AGV with navepegritide monotherapy in the ApproaCH trial (NCT05598320).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Twenty-one children were enrolled: 12 received no prior growth-promoting treatment (treatment-naive, TN) and 9 had been receiving navepegritide monotherapy for &amp;gt;1 year (navepegritide-experienced, NE). At week 52, TN children receiving navepegritide and lonapegsomatropin had a least squares mean AGV of 8.69\u2005cm\/year versus 5.95\u2005cm\/year for matched children who received navepegritide monotherapy, a difference of 2.74\u2005cm\/year (P &amp;lt; .0001). Observed mean AGV for TN children was 8.80\u2005cm\/year, a +3.89\u2005cm\/year increase from baseline (P = .0015). NE children had an observed mean AGV of 8.42\u2005cm\/year, a +3.28\u2005cm\/year increase from navepegritide-treated baseline (P &amp;lt; .0001). An improvement in body proportionality was observed and arm span increased substantially (+9.4\u2005cm in TN and +7.9\u2005cm in NE children), in line with gains in height. Treatments were well-tolerated with generally mild adverse events and no treatment discontinuations.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>In this prospective trial, the robust growth and anthropometric results suggest that by continuously relieving the pre-hypertrophic block in achondroplasia, navepegritide may make the growth plate more responsive to the strong complementary effect of lonapegsomatropin.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Trial registration details<\/jats:title>\n                    <jats:p>ClinicalTrials.gov NCT06433557<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1093\/ejendo\/lvag082","type":"journal-article","created":{"date-parts":[[2026,5,16]],"date-time":"2026-05-16T11:44:04Z","timestamp":1778931844000},"page":"745-755","source":"Crossref","is-referenced-by-count":2,"title":["Navepegritide combined with lonapegsomatropin for the treatment of children with achondroplasia: 52-week results from the phase 2 COACH trial"],"prefix":"10.1093","volume":"194","author":[{"given":"Ciara M","family":"McDonnell","sequence":"first","affiliation":[{"name":"Department of Endocrinology, Children's Health Ireland at Temple Street , Dublin 1 D01 XD99 ,","place":["Ireland"]},{"name":"Discipline of Paediatrics, University of Dublin, Trinity College , Dublin D02 PN40 ,","place":["Ireland"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Melita","family":"Irving","sequence":"additional","affiliation":[{"name":"Guy's and St.Thomas\u2019 NHS Foundation Trust, Evelina Children's Hospital , London SE1 7EH ,","place":["United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Line Aagaard","family":"Nolting","sequence":"additional","affiliation":[{"name":"Department of Pediatrics and Adolescent Medicine, Copenhagen University Hospital, Rigshospitalet , 2100 Copenhagen ,","place":["Denmark"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sohair G","family":"Abdelrahman","sequence":"additional","affiliation":[{"name":"Clinical Development, Ascendis Pharma LLC , Palo Alto, CA 94304 ,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lene Worsaae","family":"Dalby","sequence":"additional","affiliation":[{"name":"Ascendis Pharma, A\/S , 2900 Hellerup ,","place":["Denmark"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jennifer M","family":"Ikl\u00e9","sequence":"additional","affiliation":[{"name":"Clinical Development, Ascendis Pharma LLC , Palo Alto, CA 94304 ,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Simon Mejlhede","family":"Jensen","sequence":"additional","affiliation":[{"name":"Ascendis Pharma, A\/S , 2900 Hellerup ,","place":["Denmark"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Allison S","family":"Komirenko","sequence":"additional","affiliation":[{"name":"Clinical Development, Ascendis Pharma LLC , Palo Alto, CA 94304 ,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael S","family":"Ominsky","sequence":"additional","affiliation":[{"name":"Clinical Development, Ascendis Pharma LLC , Palo Alto, CA 94304 ,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aimee D","family":"Shu","sequence":"additional","affiliation":[{"name":"Clinical Development, Ascendis Pharma LLC , Palo Alto, CA 94304 ,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hanne B","family":"Hove","sequence":"additional","affiliation":[{"name":"Department of Pediatrics and Adolescent Medicine, Copenhagen University Hospital, Rigshospitalet , 2100 Copenhagen ,","place":["Denmark"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2026,5,18]]},"reference":[{"issue":"9582","key":"2026060311084071500_lvag082-B1","doi-asserted-by":"publisher","first-page":"162","DOI":"10.1016\/S0140-6736(07)61090-3","article-title":"Achondroplasia","volume":"370","author":"Horton","year":"2007","journal-title":"Lancet"},{"issue":"1","key":"2026060311084071500_lvag082-B2","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1186\/s13023-018-0972-6","article-title":"Achondroplasia: a comprehensive clinical review","volume":"14","author":"Pauli","year":"2019","journal-title":"Orphanet J Rare Dis"},{"issue":"8","key":"2026060311084071500_lvag082-B3","doi-asserted-by":"publisher","first-page":"1723","DOI":"10.1002\/ajmg.a.38853","article-title":"Growth in achondroplasia: development of height, weight, head circumference, and body mass index in a European cohort","volume":"176","author":"Merker","year":"2018","journal-title":"Am J Med Genet A"},{"issue":"2","key":"2026060311084071500_lvag082-B4","doi-asserted-by":"publisher","first-page":"364","DOI":"10.1093\/ajcn\/88.2.364","article-title":"Age-appropriate body mass index in children with achondroplasia: interpretation in relation to indexes of height","volume":"88","author":"Hoover-Fong","year":"2008","journal-title":"Am J Clin Nutr"},{"issue":"6","key":"2026060311084071500_lvag082-B5","doi-asserted-by":"publisher","first-page":"532","DOI":"10.1111\/j.1469-8749.2012.04234.x","article-title":"Development in children with achondroplasia: a prospective clinical cohort study","volume":"54","author":"Ireland","year":"2012","journal-title":"Dev Med Child Neurol"},{"key":"2026060311084071500_lvag082-B6"},{"issue":"11","key":"2026060311084071500_lvag082-B7","doi-asserted-by":"publisher","first-page":"5916","DOI":"10.3390\/ijms23115916","article-title":"Molecular mechanism of induction of bone growth by the C-type natriuretic peptide","volume":"23","author":"Rintz","year":"2022","journal-title":"Int J Mol Sci"},{"issue":"1","key":"2026060311084071500_lvag082-B8","doi-asserted-by":"publisher","first-page":"80","DOI":"10.1038\/nm971","article-title":"Overexpression of CNP in chondrocytes rescues achondroplasia through a MAPK-dependent\u2019pathway","volume":"10","author":"Yasoda","year":"2004","journal-title":"Nat Med"},{"issue":"9","key":"2026060311084071500_lvag082-B9","doi-asserted-by":"publisher","first-page":"3604","DOI":"10.1210\/en.2002-220307","article-title":"Cyclic GMP-dependent\u2019protein kinase II plays a critical role in C-type natriuretic peptide-mediated endochondral ossification","volume":"143","author":"Miyazawa","year":"2002","journal-title":"Endocrinology"},{"issue":"4","key":"2026060311084071500_lvag082-B10","doi-asserted-by":"publisher","first-page":"516","DOI":"10.1097\/MOP.0b013e32833b7a69","article-title":"Achondroplasia: pathogenesis and implications for future treatment","volume":"22","author":"Laederich","year":"2010","journal-title":"Curr Opin Pediatr"},{"issue":"1","key":"2026060311084071500_lvag082-B11","doi-asserted-by":"publisher","first-page":"18","DOI":"10.1001\/jamapediatrics.2025.4771","article-title":"Once-weekly navepegritide in children with achondroplasia: the APPROACH randomized clinical trial","volume":"180","author":"Savarirayan","year":"2025","journal-title":"JAMA Pediatr"},{"issue":"3","key":"2026060311084071500_lvag082-B12","doi-asserted-by":"publisher","first-page":"228","DOI":"10.1002\/mpo.10342","article-title":"Regulation of bone mass by growth hormone","volume":"41","author":"Olney","year":"2003","journal-title":"Med Pediatr Oncol"},{"issue":"6","key":"2026060311084071500_lvag082-B13","doi-asserted-by":"publisher","first-page":"R212","DOI":"10.1530\/EC-18-0099","article-title":"The growth hormone-insulin-like growth factor-I axis in the diagnosis and treatment of growth disorders","volume":"7","author":"Blum","year":"2018","journal-title":"Endocr Connect"},{"issue":"1","key":"2026060311084071500_lvag082-B14","doi-asserted-by":"publisher","first-page":"53","DOI":"10.1210\/edrv.22.1.0419","article-title":"The somatomedin hypothesis: 2001","volume":"22","author":"Le Roith","year":"2001","journal-title":"Endocr Rev"},{"key":"2026060311084071500_lvag082-B15","volume-title":"SKYTROFA\u00ae [package insert]","year":"2022"},{"key":"2026060311084071500_lvag082-B16","volume-title":"SKYTROFA (lonapegsomatropin-tcgd) [package insert]","year":"2021"},{"key":"2026060311084071500_lvag082-B17","doi-asserted-by":"publisher","DOI":"10.1159\/000545064","article-title":"Children with growth hormone deficiency treated with lonapegsomatropin demonstrated sustained height improvements for up to 6 years: enliGHten trial final results [published online ahead of print March 6, 2025]","author":"Maniatis","year":"2025","journal-title":"Horm Res Paediatr"},{"issue":"7","key":"2026060311084071500_lvag082-B18","doi-asserted-by":"publisher","first-page":"e2680","DOI":"10.1210\/clinem\/dgac217","article-title":"Safety and efficacy of lonapegsomatropin in children with growth hormone deficiency: enliGHten trial 2-year results","volume":"107","author":"Maniatis","year":"2022","journal-title":"J Clin Endocrinol Metab"},{"issue":"3","key":"2026060311084071500_lvag082-B19","doi-asserted-by":"publisher","first-page":"233","DOI":"10.1159\/000524003","article-title":"Switching to weekly\u2019lonapegsomatropin from daily somatropin in children with growth hormone deficiency: the fliGHt trial","volume":"95","author":"Maniatis","year":"2022","journal-title":"Horm Res Paediatr"},{"issue":"11","key":"2026060311084071500_lvag082-B20","doi-asserted-by":"publisher","first-page":"3184","DOI":"10.1210\/clinem\/dgab529","article-title":"Weekly lonapegsomatropin in treatment-naive children with growth hormone deficiency: the phase 3 heiGHt trial","volume":"106","author":"Thornton","year":"2021","journal-title":"J Clin Endocrinol Metab"},{"issue":"5","key":"2026060311084071500_lvag082-B21","doi-asserted-by":"publisher","first-page":"1673","DOI":"10.1210\/jc.2016-3776","article-title":"A randomized phase 2 study of long-acting TransCon GH vs Daily GH in childhood GH deficiency","volume":"102","author":"Chatelain","year":"2017","journal-title":"J Clin Endocrinol Metab"},{"issue":"6","key":"2026060311084071500_lvag082-B22","doi-asserted-by":"publisher","first-page":"1640","DOI":"10.1210\/clinem\/dgaf680","article-title":"Efficacy and safety of once-weekly lonapegsomatropin in adults with growth hormone deficiency: foresiGHt trial results","volume":"111","author":"Biller","year":"2026","journal-title":"J Clin Endocrinol Metab"},{"issue":"7","key":"2026060311084071500_lvag082-B23","doi-asserted-by":"publisher","first-page":"3138","DOI":"10.1210\/en.2008-1676","article-title":"Systemic administration of C-type natriuretic peptide as a novel therapeutic strategy for skeletal dysplasias","volume":"150","author":"Yasoda","year":"2009","journal-title":"Endocrinology"},{"issue":"21","key":"2026060311084071500_lvag082-B24","doi-asserted-by":"publisher","first-page":"5089","DOI":"10.1242\/jcs.02618","article-title":"Interaction of fibroblast growth factor and C-natriuretic peptide signaling in regulation of chondrocyte proliferation and extracellular matrix homeostasis","volume":"118","author":"Krejci","year":"2005","journal-title":"J Cell Sci"},{"key":"2026060311084071500_lvag082-B25","doi-asserted-by":"publisher","DOI":"10.1016\/j.eclinm.2023.102258","article-title":"Once-weekly TransCon CNP (navepegritide) in children with achondroplasia (ACcomplisH): a phase 2, multicentre, randomised, double-blind, placebo-controlled, dose-escalation trial","volume":"65","author":"Savarirayan","year":"2023","journal-title":"EClinicalMedicine"},{"issue":"11","key":"2026060311084071500_lvag082-B26","doi-asserted-by":"publisher","first-page":"4210","DOI":"10.1210\/jc.2008-0509","article-title":"Consensus statement on the diagnosis and treatment of children with idiopathic short stature: a summary of the Growth Hormone Research Society, the Lawson Wilkins Pediatric Endocrine Society, and the European Society for Paediatric Endocrinology Workshop","volume":"93","author":"Cohen","year":"2008","journal-title":"J Clin Endocrinol Metab"},{"issue":"3","key":"2026060311084071500_lvag082-B27","doi-asserted-by":"publisher","first-page":"G1","DOI":"10.1530\/eje-17-0430","article-title":"Clinical practice guidelines for the care of girls and women with Turner syndrome: proceedings from the 2016 Cincinnati International Turner Syndrome Meeting","volume":"177","author":"Gravholt","year":"2017","journal-title":"Eur J Endocrinol"},{"issue":"5","key":"2026060311084071500_lvag082-B28","doi-asserted-by":"publisher","first-page":"1712","DOI":"10.1210\/jc.2013-3059","article-title":"Reference intervals for insulin-like growth factor-1 (IGF-I) from birth to senescence: results from a multicenter study using a new automated chemiluminescence IGF-I immunoassay conforming to recent international recommendations","volume":"99","author":"Bidlingmaier","year":"2014","journal-title":"J Clin Endocrinol Metab"},{"issue":"1","key":"2026060311084071500_lvag082-B29","doi-asserted-by":"publisher","DOI":"10.1210\/jendso\/bvab168","article-title":"Average IGF-1 prediction for once-weekly lonapegsomatropin in children with growth hormone deficiency","volume":"6","author":"Lin","year":"2022","journal-title":"J Endocr Soc"},{"issue":"3","key":"2026060311084071500_lvag082-B30","doi-asserted-by":"publisher","first-page":"317","DOI":"10.1016\/s0022-3476(85)80501-1","article-title":"Clinical longitudinal standards for height and height velocity for North American children","volume":"107","author":"Tanner","year":"1985","journal-title":"J Pediatr"},{"issue":"s319","key":"2026060311084071500_lvag082-B31","doi-asserted-by":"publisher","first-page":"38","DOI":"10.1111\/j.1651-2227.1985.tb10107.x","article-title":"Growth dynamics of low-birth-weight infants","volume":"319","author":"Brandt","year":"1985","journal-title":"Acta Paediatr Scand Suppl"},{"key":"2026060311084071500_lvag082-B32","volume-title":"A Handbook of Physical Measurements","author":"Hall","year":"2007","edition":"2nd ed"},{"key":"2026060311084071500_lvag082-B33"},{"issue":"3","key":"2026060311084071500_lvag082-B34","doi-asserted-by":"publisher","first-page":"399","DOI":"10.1080\/00273171.2011.568786","article-title":"An introduction to propensity score methods for reducing the effects of confounding in observational studies","volume":"46","author":"Austin","year":"2011","journal-title":"Multivariate Behav Res"},{"key":"2026060311084071500_lvag082-B35","doi-asserted-by":"publisher","first-page":"370","DOI":"10.1093\/jbmr\/zjaf166","article-title":"Once-weekly lonapegsomatropin (TransCon hGH) added to once-weekly navepegritide (TransCon CNP) in children with achondroplasia: 26-week results from the phase 2 COACH trial","volume":"40 Suppl 1","author":"McDonnell","year":"2025"},{"issue":"1","key":"2026060311084071500_lvag082-B36","doi-asserted-by":"publisher","first-page":"25","DOI":"10.1297\/cpe.29.25","article-title":"Clinical practice guidelines for achondroplasia","volume":"29","author":"Kubota","year":"2020","journal-title":"Clin Pediatr Endocrinol"},{"issue":"7","key":"2026060311084071500_lvag082-B37","doi-asserted-by":"publisher","first-page":"873","DOI":"10.1007\/s00431-017-2923-y","article-title":"Final adult height in long-term growth hormone-treated achondroplasia patients","volume":"176","author":"Harada","year":"2017","journal-title":"Eur J Pediatr"},{"issue":"11","key":"2026060311084071500_lvag082-B38","doi-asserted-by":"publisher","first-page":"5573","DOI":"10.3390\/ijms22115573","article-title":"Advantages and disadvantages of different treatment methods in achondroplasia: a review","volume":"22","author":"Wrobel","year":"2021","journal-title":"Int J Mol Sci"},{"issue":"4","key":"2026060311084071500_lvag082-B39","doi-asserted-by":"publisher","first-page":"435","DOI":"10.1203\/00006450-199910000-00012","article-title":"Treatment of achondroplasia with growth hormone: six years of experience","volume":"46","author":"Ramaswami","year":"1999","journal-title":"Pediatr Res"},{"issue":"10","key":"2026060311084071500_lvag082-B40","doi-asserted-by":"publisher","first-page":"1402","DOI":"10.1111\/j.1651-2227.2005.tb01811.x","article-title":"Growth hormone treatment in 35 prepubertal children with achondroplasia: a five-year dose-response trial","volume":"94","author":"Hertel","year":"2005","journal-title":"Acta Paediatr"},{"issue":"6","key":"2026060311084071500_lvag082-B41","doi-asserted-by":"publisher","first-page":"P35","DOI":"10.1530\/EJE-21-1186","article-title":"Safety of growth hormone replacement in survivors of cancer and intracranial and pituitary tumours: a consensus statement","volume":"186","author":"Boguszewski","year":"2022","journal-title":"Eur J Endocrinol"},{"issue":"1","key":"2026060311084071500_lvag082-B42","doi-asserted-by":"publisher","first-page":"45","DOI":"10.1515\/jpem.1993.6.1.45","article-title":"Growth hormone (GH) treatment in achondroplasia","volume":"6","author":"Yamate","year":"1993","journal-title":"J Pediatr Endocrinol"},{"key":"2026060311084071500_lvag082-B43","doi-asserted-by":"publisher","first-page":"53","DOI":"10.1159\/000023534","article-title":"Growth hormone therapy in achondroplasia","volume":"53 Suppl 3","author":"Seino","year":"2000","journal-title":"Horm Res"}],"container-title":["European Journal of Endocrinology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/ejendo\/advance-article-pdf\/doi\/10.1093\/ejendo\/lvag082\/68317490\/lvag082.pdf","content-type":"application\/pdf","content-version":"am","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/ejendo\/article-pdf\/194\/6\/745\/68317490\/lvag082.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/ejendo\/article-pdf\/194\/6\/745\/68317490\/lvag082.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,6,3]],"date-time":"2026-06-03T15:08:48Z","timestamp":1780499328000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/ejendo\/article\/194\/6\/745\/8684122"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,5,18]]},"references-count":43,"journal-issue":{"issue":"6","published-print":{"date-parts":[[2026,6,1]]}},"URL":"https:\/\/doi.org\/10.1093\/ejendo\/lvag082","relation":{},"ISSN":["0804-4643","1479-683X"],"issn-type":[{"value":"0804-4643","type":"print"},{"value":"1479-683X","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2026,6]]},"published":{"date-parts":[[2026,5,18]]}}}