We report data from a prospective, observational study (ZAGAL) evaluating miglustat 100mg three times daily orally. in treatment-naïve patients and patients with type 1 Gaucher Disease (GD1) switched from previous enzyme replacement therapy (ERT). Clinical evolution, changes in organ size, blood counts, disease biomarkers, bone marrow infiltration (S-MRI), bone mineral density by broadband ultrasound densitometry (BMD), safety and tolerability annual reports were analysed. Between May 2004 and April 2016, 63 patients received miglustat therapy; 20 (32%) untreated and 43 (68%) switched. At the time of this report 39 patients (14 [36%] treatment-naïve; 25 [64%] switch) remain on miglustat. With over 12-year follow-up, hematologic counts, liver and spleen volumes remained stable. In total, 80% of patients achieved current GD1 therapeutic goals. Plasma chitotriosidase activity and CCL-18/PARC concentration showed a trend towards a slight increase. Reductions on S-MRI (p=0.042) with an increase in BMD (p<0.01) were registered. Gastrointestinal disturbances were reported in 25/63 (40%), causing miglustat suspension in 11/63 (17.5%) cases. Thirty-eight patients (60%) experienced a fine hand tremor and two a reversible peripheral neuropathy. Overall, miglustat was effective as a long-term therapy in mild to moderate naïve and ERT stabilized patients. No unexpected safety signals were identified during 12-years follow-up.

No abstract

Background and objectives: Several reports describe the use of miglustat (Zavesca®), an oral inhibitor of glucosylceramide synthase, for type 1 Gaucher disease (GD1) in clinical trials. There are few data on the use of miglustat for GD1 in the real-world clinical experience. Here, we assess the long-term efficacy, tolerability and safety of miglustat in a prospective, open-label, observational study of GD1 patients attending routine clinic visits. Design and Methods: 48 patients with mild-to-moderate GD1 received miglustat 100 mg t.i.d. over 36 months. Patients were analysed in two groups: therapy-naïve patients (n = 11) and those switched from previous treatment with enzyme replacement therapy (ERT; n = 37). Assessments of clinical status, haematological parameters, and organomegaly were performed before treatment and after 6, 12, 24 and 36 months of therapy. Data were compared with a historical reference cohort 29 GD1 patients treated for 36 months with ERT. Results: Nine treatment-naïve patients completed 36 months of miglustat therapy. Sustained improvements in haemoglobin were seen in all patients who had anaemia before treatment. Platelet counts improved in patients with initial thrombocytopenia, and were maintained in patients with normal counts at baseline. Plasma chitotriosidase activity decreased in treatment-naïve patients during the first year on therapy and remained stable thereafter. S-MRI findings indicated improved bone status at 36 months. In patients switched from ERT, 15 completed 36 months of miglustat therapy, and displayed maintained or improved clinical and haematological parameters, and surrogate disease severity markers. No statistically significant differences were observed at 36 months between treatmentnaïve patients with similar baseline characteristics treated with either miglustat or ERT. Overall, miglustat was well tolerated. Interpretation and conclusions: Miglustat provided appreciable therapeutic responses on clinical, haematological, biomarker and S-MRI parameters at 36 months in patients with GD1, and was well tolerated. Therapeutic responses with miglustat were comparable with those seen with ERT.