About miglustat
Miglustat (Zavesca®) is a low molecular weight inhibitor of glucosylceramide synthase and α-glucosidase. Zavesca® is approved for the oral treatment of adult patients with mild to moderate type 1 Gaucher disease, and may only be used in those patients for whom enzyme replacement therapy is unsuitable. It is approved for this indication in 39 countries including the US and EU since 2003. Zavesca® is also approved in the EU for the treatment of progressive neurological manifestations in adult and pediatric patients with Niemann-Pick type C disease.
Miglustat in development for type 1 Gaucher disease
Current status
The MAINTENANCE study is evaluating the long-term safety and efficacy of miglustat as maintenance therapy after a switch from enzyme replacement therapy (ERT) in mild-to-moderate adult type 1 Gaucher disease patients with stable disease. Enrollment in the MAINTENANCE trial was completed during the second quarter of 2008. Results of this study are expected to become available in the second half of 2010.
Available clinical data
Zavesca® (miglustat) 100 mg is the only oral drug available for the treatment of type 1 Gaucher disease, and was approved on the basis of three international open-label clinical trials. The rationale for the use of miglustat in type 1 Gaucher disease is to help balance the overall level of glucosylceramide by reducing its production to a level compatible with breakdown by residual glucocerebrosidase activity, a unique mode of action known as "substrate reduction therapy". Bone manifestations of type 1 Gaucher disease were evaluated in three open-label clinical studies in patients treated with miglustat 100 mg t.i.d. for up to two years (n = 72). In a pooled analysis of uncontrolled data, bone mineral density Z-scores at the lumbar spine and femoral neck increased by more than 0.1 units from baseline in 27 (57%) and 28 (65%) of the patients with longitudinal bone density measurements. There were no events of bone crisis, avascular necrosis or fracture during the treatment period.
Milestones
2008 – EU approval for a type II variation for miglustat and bone disease in type 1 Gaucher disease
2004 – Zavesca® launched in the US and Switzerland
2003 – Zavesca® launched in the EU
2002 – Zavesca® in-licensed; marketing authorization granted by European Commission
Key scientific literature
Pastores G.M. et al. Effect of miglustat on bone disease in adult patients with type 1 Gaucher disease: a pooled analysis of three multinational Open-label studies. Clinical Therapeutics. 29: 1645-53; 2007.
Elstein D. et al. Oral maintenance clinical trial with miglustat for type 1 Gaucher disease: switch from or combination with intravenous enzyme replacement. Blood. 110: 2296-2301; 2007.
Giraldo P. et al. Short-term effect of miglustat in every day clinical use in treatment-naïve or previously treated patients with type 1 Gaucher’s disease. Haematologica. 91:125-8; 2006.
Elstein D. et al. Sustained therapeutic effects of oral miglustat (Zavesca, N-butyldeoxynojirimycin, OGT 918) in type 1 Gaucher disease.. J Inherit Metab Dis 27: 757-66; 2004.
