EU/3/06/351: Orphan designation for the treatment of Niemann-Pick's disease, type C

Niemann-Pick disease comprises a group of inherited lysosomal storage disorders. Lysosomes are small vesicles within each cell containing enzymes, proteins that are able to destroy or transform different substances of the cell, such as other proteins, fats, nucleic acids (components of the genetic material) and sugars. When there is an alteration of one of the lysosomal enzymes there is abnormal accumulation of the product (the so called substrate) that is not transformed by this particular enzyme. This means that the cells are unable to destroy or eliminate these substrates, resulting in cell damage and malfunction of the organ where the product is accumulated. In Niemann-Pick type C the lysosomal enzyme alteration affects fatty products. The symptomatology and the severity of the disease depends very much on the level of accumulation of fatty substrates such as glycosphingolipids. This accumulation usually induces progressive degeneration of the nervous system and enlargement of some organs like the liver. Niemann-Pick disease type C is chronically debilitating and life threatening.

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 47,000 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 25), Norway, Iceland and Liechtenstein. At the time of designation, this represented a population of 468,900,000 (Eurostat 2006).

At the time of submission of the application for orphan designation, no satisfactory method had been authorised in the European Union for treatment of the condition.

Miglustat is expected to block (inhibit) the action of an enzyme (glucosylceramide synthase) involved in the production of one of the substrates, the glycosphingolipids that accumulated in Niemann-Pick disease type C. It is expected that if the amount of the accumulated substance will decrease, it might help to limit the extent of the damage and the clinical consequences of the disease.

At the time of submission of the application for orphan designation, clinical trials in patients with Niemann-Pick type C were ongoing.

Miglustat was not authorised anywhere worldwide for Niemann-Pick type C, at the time of submission. Orphan designation of miglustat was previously granted in the EU for Gaucher disease.

In accordance with Regulation (EC) No 141/2000 of 16 December 1999, the COMP adopted a positive opinion on 11 January 2006 recommending the granting of this designation.

Update: Miglustat (Zavesca) has been authorised in the EU since 26 January 2009 for the treatment of progressive neurological manifestations in adult patients and paediatric patients with Niemann-Pick type C disease.

• 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 Community) or insufficient returns on investment.

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