{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,18]],"date-time":"2026-05-18T11:30:57Z","timestamp":1779103857204,"version":"3.51.4"},"reference-count":17,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2023,9,27]],"date-time":"2023-09-27T00:00:00Z","timestamp":1695772800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["accp1.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The Journal of Clinical Pharma"],"published-print":{"date-parts":[[2024,2]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Here, we report the clinical pharmacology data from LUMINA\u20101 (NCT03188666), a Phase 2 trial that evaluated garetosmab (a monoclonal antibody against activin A) in patients with fibrodysplasia ossificans progressiva. Forty\u2010four patients were randomly assigned to intravenous 10\u00a0mg\/kg of garetosmab or placebo every 4 weeks in a double\u2010blind 28\u2010week treatment period, followed by a 28\u2010week open\u2010label treatment period with garetosmab, and subsequent open\u2010label extension. Serum samples were obtained to assess pharmacokinetics (PK), immunogenicity, and bone morphogenetic protein 9 (BMP9). Comparative exposure\u2013response analyses for efficacy and safety were performed with trough concentrations (C<jats:sub>trough<\/jats:sub>) of garetosmab prior to dosing. Steady\u2010state PK was reached 12\u201016 weeks after the first dose of garetosmab, with mean (standard deviation) C<jats:sub>trough<\/jats:sub> of 105 \u00b1 30.8 mg\/L. Immunogenicity assessments showed anti\u2010garetosmab antibody formation in 1 patient (1\/43; 2.3%); titers were low, and did not affect PK or clinical efficacy. Median concentrations of BMP9 in serum were approximately 40 pg\/mL at baseline. There were no meaningful differences in PK or BMP9 concentration\u2013time profiles between patients who did and did not experience epistaxis or death. The comparative exposure\u2013response analyses demonstrated no association between C<jats:sub>trough<\/jats:sub> and efficacy or safety. PK findings were consistent with prior data in healthy volunteers and were typical for a monoclonal antibody administered at doses sufficient to saturate target\u2010mediated clearance. There were no trends that suggested patients with higher serum exposures to garetosmab were more likely to experience a reduction in heterotopic ossification or adverse events. Garetosmab is being further evaluated in the Phase 3 OPTIMA trial.<\/jats:p>","DOI":"10.1002\/jcph.2344","type":"journal-article","created":{"date-parts":[[2023,9,11]],"date-time":"2023-09-11T08:58:20Z","timestamp":1694422700000},"page":"264-274","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Garetosmab in Fibrodysplasia Ossificans Progressiva: Clinical Pharmacology Results from the Phase 2 LUMINA\u20101 Trial"],"prefix":"10.1002","volume":"64","author":[{"given":"Yuhuan","family":"Wang","sequence":"first","affiliation":[{"name":"Regeneron Pharmaceuticals  Tarrytown NY USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jenny\u2010Hoa","family":"Nguyen","sequence":"additional","affiliation":[{"name":"Regeneron Pharmaceuticals  Tarrytown NY USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ruben D.","family":"de Ruiter","sequence":"additional","affiliation":[{"name":"Department of Endocrinology and Metabolism Amsterdam University Medical Centers (UMC) Vrije Universiteit Amsterdam UMC Expert Center in Rare Bone Disease Amsterdam Movement Sciences  Amsterdam The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jeanne","family":"Mendell","sequence":"additional","affiliation":[{"name":"Regeneron Pharmaceuticals  Tarrytown NY USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dushyanth","family":"Srinivasan","sequence":"additional","affiliation":[{"name":"Regeneron Pharmaceuticals  Tarrytown NY USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"John D.","family":"Davis","sequence":"additional","affiliation":[{"name":"Regeneron Pharmaceuticals  Tarrytown NY USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"E. Marelise W.","family":"Eekhoff","sequence":"additional","affiliation":[{"name":"Department of Endocrinology and Metabolism Amsterdam University Medical Centers (UMC) Vrije Universiteit Amsterdam UMC Expert Center in Rare Bone Disease Amsterdam Movement Sciences  Amsterdam The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2023,9,27]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/icb.2011.32"},{"key":"e_1_2_11_3_1","doi-asserted-by":"publisher","DOI":"10.1159\/000365770"},{"key":"e_1_2_11_4_1","doi-asserted-by":"publisher","DOI":"10.2106\/JBJS.I.00705"},{"key":"e_1_2_11_5_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng1783"},{"key":"e_1_2_11_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cellsig.2016.10.001"},{"key":"e_1_2_11_7_1","doi-asserted-by":"publisher","DOI":"10.1186\/1750-1172-8-190"},{"key":"e_1_2_11_8_1","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.54582"},{"key":"e_1_2_11_9_1","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.aac4358"},{"key":"e_1_2_11_10_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcph.1638"},{"key":"e_1_2_11_11_1","doi-asserted-by":"publisher","DOI":"10.1002\/psp4.12224"},{"key":"e_1_2_11_12_1","doi-asserted-by":"crossref","unstructured":"Di RoccoM Forleo\u2010NetoE PignoloR et\u00a0al.Garetosmab an inhibitor of activin A reduces heterotopic ossification and flare\u2010ups in adults with fibrodysplasia ossificans progressiva: a randomized double\u2010blind placebo\u2010controlled phase 2 trial. medRxiv.2023.01.11.23284254.","DOI":"10.1101\/2023.01.11.23284254"},{"key":"e_1_2_11_13_1","unstructured":"US Food andDrugAdministration.Immunogenicity Testing of Therapeutic Protein Products \u2013 Developing and Validating Assays for Anti\u2010Drug Antibody Detection. Accessed February 23 2023.https:\/\/www.fda.gov\/regulatory\u2010information\/search\u2010fda\u2010guidance\u2010documents\/immunogenicity\u2010testing\u2010therapeutic\u2010protein\u2010products\u2010developing\u2010and\u2010validating\u2010assays\u2010anti\u2010drug."},{"key":"e_1_2_11_14_1","doi-asserted-by":"publisher","DOI":"10.1002\/psp4.12015"},{"key":"e_1_2_11_15_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0000000000001070"},{"key":"e_1_2_11_16_1","doi-asserted-by":"publisher","DOI":"10.1002\/mus.23539"},{"key":"e_1_2_11_17_1","doi-asserted-by":"publisher","DOI":"10.1359\/jbmr.081208"},{"key":"e_1_2_11_18_1","doi-asserted-by":"publisher","DOI":"10.1038\/ejhg.2009.35"}],"container-title":["The Journal of Clinical Pharmacology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/accp1.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/jcph.2344","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,1,29]],"date-time":"2024-01-29T08:55:59Z","timestamp":1706518559000},"score":1,"resource":{"primary":{"URL":"https:\/\/accp1.onlinelibrary.wiley.com\/doi\/10.1002\/jcph.2344"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,9,27]]},"references-count":17,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2024,2]]}},"alternative-id":["10.1002\/jcph.2344"],"URL":"https:\/\/doi.org\/10.1002\/jcph.2344","archive":["Portico"],"relation":{},"ISSN":["0091-2700","1552-4604"],"issn-type":[{"value":"0091-2700","type":"print"},{"value":"1552-4604","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,9,27]]},"assertion":[{"value":"2023-05-23","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2023-09-06","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2023-09-27","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}