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Efficacy and safety of arimoclomol in Niemann-Pick disease type C: Results from a double-blind, randomised, placebo-controlled, multinational phase 2/3 trial of a novel treatment

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  • Eugen Mengel
  • Marc C Patterson
  • Rosalia M Da Riol
  • Mireia Del Toro
  • Federica Deodato
  • Matthias Gautschi
  • Stephanie Grunewald
  • Sabine Grønborg
  • Paul Harmatz
  • Bénédicte Héron
  • Esther M Maier
  • Agathe Roubertie
  • Saikat Santra
  • Anna Tylki-Szymanska
  • Simon Day
  • Anne Katrine Andreasen
  • Marie Aavang Geist
  • Nikolaj Havnsøe Torp Petersen
  • Linda Ingemann
  • Thomas Hansen
  • Thomas Blaettler
  • Thomas Kirkegaard
  • Christine Í Dali
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Niemann-Pick 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-month, prospective, randomised, double-blind, placebo-controlled, phase 2/3 trial ( identifier: NCT02612129), patients (2-18 years) 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-domain NPC Clinical Severity Scale (NPCCSS) score from baseline to 12 months. Fifty patients enrolled; 42 completed. At month 12, the mean progression from baseline in the 5-domain NPCCSS was 0.76 with arimoclomol vs 2.15 with placebo. A statistically significant treatment difference in favour of arimoclomol of -1.40 (95% confidence interval: -2.76, -0.03; P = .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 months with a treatment difference of -2.06 in favour of arimoclomol (P = .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-related serious adverse events (n = 2) included urticaria and angioedema. Arimoclomol provided a significant and clinically meaningful treatment effect in NPC and was well tolerated.

TidsskriftJournal of Inherited Metabolic Disease
Udgave nummer6
Sider (fra-til)1463-1480
Antal sider18
StatusUdgivet - nov. 2021

Bibliografisk note

© 2021 The Authors. Journal of Inherited Metabolic Disease published by John Wiley & Sons Ltd on behalf of SSIEM.

ID: 73464976