Short-Term Effect of Oral Treatment with Miglustat in Type 1 Gaucher Disease.

Background and objective Miglustat (Zavesca^®), an inhibitor of the enzyme glucosylceramide synthase, is an orally active molecule that has been shown to be a safe and effective therapy for type I GD. Here we report on our experience of miglustat monotherapy for the treatment of type 1 Gaucher disease (GD) patients in Spain.

Design and Methods: We designed a prospective, open-label study of 21 patients with mild-to- moderate type 1 GD, to investigate the efficacy and tolerability of miglustat over a 12-month period in therapy-naïve patients and in patients who have previously received enzyme replacement therapy (ERT). Clinical assessments, including haematological parameters and organomegaly, were carried out prior to and after 6 and 12 months of miglustat therapy. In addition, the results were compared with data analysed retrospectively from 40 patients with type 1 GD who had been treated for 6 months with ERT. The data following 6 months of miglustat therapy are presented here.

Results At present, 16 patients have completed 6 months of miglustat treatment. All patients with anaemia had improved haemoglobin concentrations, and in the treatment-naive group a mean increase of 1 g/dl was observed. Platelet counts improved in patients with thrombocytopenia and were maintained in patients with counts within normal limits at baseline. Chitotriosidase activity was maintained in switched patients and decreased in naïve patients. Miglustat was well tolerated, and the efficacy after 6 months therapy was comparable to that observed in the clinical trials and in patients treated with ERT for 6 months. Interpretation and conclusions In our experience, properly selected patients with mild to moderate type I GD had a satisfactory clinical and biochemical response to 6 months of miglustat therapy. The therapy was well tolerated, and clinical benefits were comparable to those obtained with ERT.