{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T20:06:17Z","timestamp":1792785977538,"version":"4.5.0"},"reference-count":39,"publisher":"Oxford University Press (OUP)","issue":"10","license":[{"start":{"date-parts":[[2026,8,29]],"date-time":"2026-08-29T00:00:00Z","timestamp":1787961600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Clementia Pharmaceuticals Inc.","id":[{"id":"https:\/\/ror.org\/01h2nq698","id-type":"ROR","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,8,30]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Palovarotene is approved in several countries for reducing heterotopic ossification (HO) in patients with fibrodysplasia ossificans progressiva (FOP), an ultra-rare, severely debilitating, genetic disorder. Approval was based on interim phase III MOVE trial (NCT03312634) analyses at month 18 (IA3), the most complete dataset considering subsequent clinical holds for futility and study restart; however, long-term data remain limited. We report exploratory, post hoc analyses of once daily palovarotene over the 48-mo MOVE trial, including time on and off treatment. The primary efficacy outcome was annualized change in new HO volume, per low-dose whole-body CT. Safety was assessed throughout. Post-baseline HO volume measurements were available for 97 palovarotene-treated patients from MOVE and 101 untreated patients from a natural history study (NHS; NCT02322255). Across 48\u00a0mo, mean annualized new HO volume was numerically lower (46.4%) in palovarotene-treated patients compared with untreated patients; however, this difference was not significant (nominal p\u2009=\u2009.0585). In patients who paused and stopped or paused and restarted palovarotene, mean annualized new HO volume appeared lower when patients received palovarotene compared with when they did not (significance not assessed). The proportions of patients with new HO and number of affected body regions were similar in palovarotene-treated patients and untreated patients (significance not assessed); flare-up rates were consistent with published literature. Adverse events were predominantly retinoid-associated mucocutaneous events. In 80 patients aged &amp;lt;18\u00a0yr in MOVE, palovarotene treatment occurred for a mean (SD) of 166.0 (75.2) wk; 24 (30.0%), all aged &amp;lt;14\u00a0yr, had premature physeal closure events. Computational analyses showed a significantly increased risk of radiographically-observed, asymptomatic new-onset vertebral deformities with palovarotene treatment. Overall, these exploratory analyses reaffirm the MOVE IA3 findings but should be interpreted with caution; potential efficacy must be weighed against the safety profile of palovarotene, particularly in growing patients. Clinical trial registration number: NCT03312634 (MOVE), NCT02322255 (NHS), and NCT02279095 (phase II OLE).<\/jats:p>","DOI":"10.1093\/jbmrpl\/ziag141","type":"journal-article","created":{"date-parts":[[2026,8,29]],"date-time":"2026-08-29T17:40:22Z","timestamp":1788025222000},"source":"Crossref","is-referenced-by-count":0,"title":["Palovarotene impact on fibrodysplasia ossificans progressiva (FOP): data from month 48 of the phase III MOVE trial"],"prefix":"10.1093","volume":"10","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8533-9438","authenticated-orcid":false,"given":"Robert J","family":"Pignolo","sequence":"first","affiliation":[{"name":"Department of Medicine, Mayo Clinic , Rochester, MN 55905 ,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8924-106X","authenticated-orcid":false,"given":"Edward C","family":"Hsiao","sequence":"additional","affiliation":[{"name":"Division of Endocrinology and Metabolism, the UCSF Metabolic Bone Clinic, the Eli and Edyth Broad Institute for Regeneration Medicine, and the Institute of Human Genetics, Department of Medicine, and the UCSF Program in Craniofacial Biology, University of California San Francisco , San Francisco, CA 94143 ,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7138-596X","authenticated-orcid":false,"given":"Mona","family":"Al Mukaddam","sequence":"additional","affiliation":[{"name":"Departments of Orthopaedic Surgery and Medicine, Center for Research in FOP and Related Disorders, Perelman School of Medicine, University of Pennsylvania , Philadelphia, PA 19104 ,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7435-0298","authenticated-orcid":false,"given":"Genevi\u00e8ve","family":"Baujat","sequence":"additional","affiliation":[{"name":"Service de M\u00e9decine G\u00e9nomique des Maladies Rares, H\u00f4pital Necker-Enfants Malades , Paris 71015 ,","place":["France"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9263-9578","authenticated-orcid":false,"given":"Staffan K","family":"Berglund","sequence":"additional","affiliation":[{"name":"Department of Clinical Sciences, Pediatrics, Ume\u00e5 University , 901 87 Ume\u00e5 ,","place":["Sweden"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8332-0744","authenticated-orcid":false,"given":"Angela M","family":"Cheung","sequence":"additional","affiliation":[{"name":"Department of Medicine and Joint Department of Medical Imaging, University Health Network, University of Toronto , Toronto, ON M5G ,","place":["Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1306-1852","authenticated-orcid":false,"given":"Carmen","family":"De Cunto","sequence":"additional","affiliation":[{"name":"Pediatric Rheumatology Section, Department of Pediatrics, Hospital Italiano de Buenos Aires , Buenos Aires C1199ACH ,","place":["Argentina"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2841-493X","authenticated-orcid":false,"given":"Patricia","family":"Delai","sequence":"additional","affiliation":[{"name":"Centro de Pesquisa Clinica, Hospital Israelita Albert Einstein , S\u00e3o Paulo 05652-000 ,","place":["Brazil"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7806-7641","authenticated-orcid":false,"given":"Nobuhiko","family":"Haga","sequence":"additional","affiliation":[{"name":"Department of Rehabilitation Medicine, The University of Tokyo Hospital , Tokyo 113-8655 ,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9479-4232","authenticated-orcid":false,"given":"Peter","family":"Kannu","sequence":"additional","affiliation":[{"name":"Hospital for Sick Children , Toronto, ON M5G 1E8 ,","place":["Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1540-3745","authenticated-orcid":false,"given":"Edna E","family":"Mancilla","sequence":"additional","affiliation":[{"name":"Children\u2019s Hospital of Philadelphia, Perelman School of Medicine, University of Pennsylvania , Philadelphia, PA 19104 ,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-5255-2023","authenticated-orcid":false,"given":"Rose","family":"Marino","sequence":"additional","affiliation":[{"name":"Ipsen , Cambridge, MA 02142 ,","place":["United 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