{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,21]],"date-time":"2026-10-21T12:51:59Z","timestamp":1792587119275,"version":"4.5.0"},"reference-count":43,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2021,9,7]],"date-time":"2021-09-07T00:00:00Z","timestamp":1630972800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J of Inher Metab Disea"],"published-print":{"date-parts":[[2021,11]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Niemann\u2010Pick disease type C (NPC) is a rare, genetic, progressive neurodegenerative disorder with high unmet medical need. We investigated the safety and efficacy of arimoclomol, which amplifies the heat shock response to target NPC protein misfolding and improve lysosomal function, in patients with NPC. In a 12\u2010month, prospective, randomised, double\u2010blind, placebo\u2010controlled, phase 2\/3 trial (<jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"http:\/\/clinicaltrials.gov\">ClinicalTrials.gov<\/jats:ext-link> identifier: NCT02612129), patients (2\u201018\u2009years) were randomised 2:1 to arimoclomol:placebo, stratified by miglustat use. Routine clinical care was maintained. Arimoclomol was administered orally three times daily. The primary endpoint was change in 5\u2010domain NPC Clinical Severity Scale (NPCCSS) score from baseline to 12\u2009months. Fifty patients enrolled; 42 completed. At month 12, the mean progression from baseline in the 5\u2010domain NPCCSS was 0.76 with arimoclomol vs 2.15 with placebo. A statistically significant treatment difference in favour of arimoclomol of \u22121.40 (95% confidence interval: \u22122.76, \u22120.03; <jats:italic>P<\/jats:italic>\u00a0=\u00a0.046) was observed, corresponding to a 65% reduction in annual disease progression. In the prespecified subgroup of patients receiving miglustat as routine care, arimoclomol resulted in stabilisation of disease severity over 12\u2009months with a treatment difference of \u22122.06 in favour of arimoclomol (<jats:italic>P<\/jats:italic>\u00a0=\u00a0.006). Adverse events occurred in 30\/34 patients (88.2%) receiving arimoclomol and 12\/16 (75.0%) receiving placebo. Fewer patients had serious adverse events with arimoclomol (5\/34, 14.7%) vs placebo (5\/16, 31.3%). Treatment\u2010related serious adverse events (n\u00a0=\u00a02) included urticaria and angioedema. Arimoclomol provided a significant and clinically meaningful treatment effect in NPC and was well tolerated.<\/jats:p>","DOI":"10.1002\/jimd.12428","type":"journal-article","created":{"date-parts":[[2021,8,21]],"date-time":"2021-08-21T20:45:31Z","timestamp":1629578731000},"page":"1463-1480","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":99,"title":["Efficacy and safety of arimoclomol in <scp>Niemann\u2010Pick<\/scp> disease type C: Results from a double\u2010blind, randomised, placebo\u2010controlled, multinational phase 2\/3 trial of a novel treatment"],"prefix":"10.1002","volume":"44","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8967-2951","authenticated-orcid":false,"given":"Eugen","family":"Mengel","sequence":"first","affiliation":[{"name":"SphinCS GmbH Institute of Clinical Science for LSD  Hochheim Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marc C.","family":"Patterson","sequence":"additional","affiliation":[{"name":"Departments of Neurology, Pediatrics and Medical Genetics Mayo Clinic  Rochester Minnesota USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rosalia M.","family":"Da Riol","sequence":"additional","affiliation":[{"name":"Regional Coordination Center for Rare Diseases Academic Hospital \u2018Santa Maria della Misericordia\u2019  Udine Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mireia","family":"Del Toro","sequence":"additional","affiliation":[{"name":"Pediatric Neurology Department Vall d'Hebron University Hospital  Barcelona Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Federica","family":"Deodato","sequence":"additional","affiliation":[{"name":"Division of Metabolism Ospedale Pediatrico Bambino Ges\u00f9, IRCCS  Rome Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthias","family":"Gautschi","sequence":"additional","affiliation":[{"name":"Department of Paediatrics, Division of Endocrinology, Diabetology and Metabolism, and Institute of Clinical Chemistry, Inselspital University Hospital Bern, University of Bern  Bern Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephanie","family":"Grunewald","sequence":"additional","affiliation":[{"name":"Department of Metabolic Medicine Great Ormond Street Hospital, Institute of Child Health, UCL, NIHR Biomedical Research Center  London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sabine","family":"Gr\u00f8nborg","sequence":"additional","affiliation":[{"name":"Centre for Inherited Metabolic Diseases Copenhagen University Hospital (Rigshospitalet)  Copenhagen Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paul","family":"Harmatz","sequence":"additional","affiliation":[{"name":"Gastroenterology and Hepatology UCSF Benioff Children's Hospital Oakland  Oakland California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"B\u00e9n\u00e9dicte","family":"H\u00e9ron","sequence":"additional","affiliation":[{"name":"Department of Pediatric Neurology, Reference Centre for Lysosomal Diseases University Hospital Armand Trousseau  Paris France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Esther M.","family":"Maier","sequence":"additional","affiliation":[{"name":"Department of Inborn Errors of Metabolism University of Munich Children's Hospital  Munich Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Agathe","family":"Roubertie","sequence":"additional","affiliation":[{"name":"Department of Neuropediatrics Centre Hospitalier Universitaire de Montpellier  Montpellier France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Saikat","family":"Santra","sequence":"additional","affiliation":[{"name":"Department of Inherited Metabolic Disorders Birmingham Children's Hospital  Birmingham UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna","family":"Tylki\u2010Szymanska","sequence":"additional","affiliation":[{"name":"Department of Paediatrics, Nutrition and Metabolic Diseases The Children's Memorial Institute  Warsaw Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Simon","family":"Day","sequence":"additional","affiliation":[{"name":"Biostatistics Clinical Trials Consulting &amp; 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