NP-C is a rare genetic disease with significant neurological deterioration that can be fatal and affects infants, children and adults [1,2]. Neurological deterioration is the key feature of NP-C, which manifests in a variety of symptoms including eye movement disorders (vertical supranuclear gaze palsy progressing to horizontal saccadic eye movement, or HSEM, problems), balance disorders (ataxia), difficulty swallowing (dysphagia), slurred and irregular speech (dysarthria), a lack of muscle control (dystonia) and seizures. Intellectual decline, which often leads to dementia, is also common, and in the final stages of the disease, the patient is often bedridden [1,3].
In a clinical trial (OGT918-007) in which patients were given either 200mg of Zavesca three times a day (in paediatric patients, the dose was adjusted to body surface area) or standard of care for 12 months, the majority of these patients’ symptoms were seen to improve or stabilize. This included the primary endpoint of HSEM velocity (the ability to move eyes rapidly from side to side), as well as other endpoints of swallowing capacity; hearing ability and mobility [4].
In an extension study in which all patients were treated with Zavesca for a further 12 months, adult and juvenile patients with NP-C were seen to stabilize in important markers of neurological disease progression. Mobility remained stable in 67% of patients, and swallowing capacity was improved or stable in 79% of patients with water, 86% of patients with puree, and 93% of patients with both soft lumps (pasta) and cookies [5].
Ed Wraith, M.D., Royal Manchester Children's Hospital, commented: ‘For the first time we have an approved therapy for NP-C. The data on the effects of treatment with Zavesca obtained in a clinical trial and in a retrospective cohort study consistently showed a favorable clinical response.’
Zavesca® is indicated for the treatment of progressive neurological manifestations in adult patients and paediatric patients with Niemann-Pick type C disease [6].
References
1 Wraith, J.E. and Imrie, J. (2007) Understanding Niemann-Pick disease type C and its potential treatment. Blackwell Publishing
2 Patterson, M.C. Niemann-Pick disease Type C. Gene Reviews 2007a (updated 9 July). Accessible at www.geneclinics.org. Accessed October 2008
3 Patterson, M.C. (2003) A riddle wrapped in a mystery: understanding Niemann-Pick disease, type C. Neurologist 9, 301–310
4 Patterson, M.C. et al. (2007) Miglustat for treatment of Niemann-Pick C disease: a randomised controlled study. Lancet Neurol. 6, 765–772
5 Patterson M.C. et al. (2008) Miglustat in Niemann-Pick disease Type C (NP-C): long-term data from a clinical trial. Proceedings of 58th Annual meeting of the American Society of Human Genetics, Abstract 766
6 Zavesca Summary of Product Characteristics. Accessible at www.emc.medicines.org.uk. Accessed March 2009