EU/3/13/1124: Orphan designation for the treatment of Niemann-Pick's disease, type C

Niemann-Pick disease is a group of inherited disorders belonging to the larger family of metabolic disorders called 'lysosomal storage diseases', in which fats accumulate within lysosomes (partS of the body's cells that break down nutrients and other materials).

In Niemann-Pick disease type C, there is a lack of transporter proteins that are needed to move fatty substances such as cholesterol and other fats within cells, leading to their build-up in the brain and elsewhere in the body (such as the spleen and liver). This causes a wide range of symptoms, including behavioural problems, learning disabilities and difficulty moving and speaking.

Niemann-Pick disease type C is chronically debilitating and life threatening since the build-up of fatty substances can cause brain damage and swelling of organs such as the spleen and the liver.

At the time of designation, Niemann-Pick disease, type C affected approximately 0.1 in 10,000 people in the European Union (EU). This was equivalent to a total of around 5,000 people*, and is below the ceiling for orphan designation, which is 5 people in 10,000. This is based on the information provided by the sponsor and the knowledge of the Committee for Orphan Medicinal Products (COMP).

*Disclaimer: For the purpose of the designation, the number of patients affected by the condition is estimated and assessed on the basis of data from the European Union (EU 28), Norway, Iceland and Liechtenstein. At the time of designation, this represented a population of 512,200,000 (Eurostat 2013).

At the time of designation, Zavesca (miglustat) was authorised in the EU to treat Niemann-Pick disease, type C.

The sponsor has provided sufficient information to show that 2-hydroxypropyl-β-cyclodextrin might be of significant benefit for patients with Niemann-Pick disease, type C because results from studies in experimental models show that it might improve survival of patients with this condition when used in combination with existing treatment. This assumption will need to be confirmed at the time of marketing authorisation, in order to maintain the orphan status.

2-Hydroxypropyl-β-cyclodextrin is a cyclic oligosaccharide (a type of carbohydrate). In Niemann-Pick disease type C, it is expected to reduce the accumulation of fats in the lysosomes by forming a complex with the cholesterol inside the lysosomes, which allows the fats to leave the lysosomes and enter into the wider cell, where they can be processed normally.

The effects of 2-hydroxypropyl-β-cyclodextrin have been evaluated in experimental models.

At the time of submission of the application for orphan designation, no clinical trials with 2-hydroxypropyl-β-cyclodextrin in patients with Niemann-Pick disease type C had been started.

At the time of submission, 2-hydroxypropyl-β-cyclodextrin was not authorised anywhere in the EU for Niemann-Pick disease type C. Orphan designation of the medicine has been granted in the United States for this condition.

In accordance with Regulation (EC) No 141/2000 of 16 December 1999, the COMP adopted a positive opinion on 13 March 2013 recommending the granting of this designation.

• the seriousness of the condition;
• the existence of alternative methods of diagnosis, prevention or treatment;
• either the rarity of the condition (affecting not more than 5 in 10,000 people in the EU) or insufficient returns on investment.

Designated orphan medicinal products are products that are still under investigation and are considered for orphan designation on the basis of potential activity. An orphan designation is not a marketing authorisation. As a consequence, demonstration of quality, safety and efficacy is necessary before a product can be granted a marketing authorisation.