Miglustat in adult and juvenile patients with Niemann–Pick disease type C: Long-term data from a clinical trial

A randomized, controlled trial of miglustat indicated that miglustat (Zavesca®) stabilized neurological disease over 12 months in adult and juvenile patients with Niemann–Pick disease type C (NP-C). We report data from a non-controlled, open-label extension to this initial randomized trial. All patients completing the randomized trial were allowed to continue treatment in a 12-month, non-controlled open-label extension. Those completing 12 months of extension therapy could continue further on miglustat in a 'continued extension' phase. From a total of 29 patients in the randomized phase (mean [±SD] age 24.6 ± 9.1 years; 52% female), 21 completed 12 months of therapy with miglustat (17 of whom received miglustat in the initial randomized phase, and four in the extension phase), and 15 patients (all from the miglustat-randomized group) completed 24 months on miglustat. Mean horizontal saccadic eye movement velocity (HSEM-α) indicated improvement in the 12-month miglustat group, and stabilization in the 24-month group; swallowing was improved or stable in 86% and in up to 93%, respectively. Ambulation was stabilized in both the 12- and 24-month groups. In an exploratory disease stability analysis of prospective data on key parameters of disease progression (HSEM-α, swallowing, ambulation and cognition), 13/19 (68%) patients receiving ⩾12 months' miglustat therapy had stable disease. Among all patients receiving ⩾1 dose of miglustat (n = 28), the most frequent adverse events were diarrhoea, weight decrease, flatulence and tremor. Overall, these data suggest that long-term miglustat therapy stabilizes neurological disease and is well tolerated in adult and juvenile patients with NP-C.