EU/3/17/1878: Orphan designation for the treatment of Niemann-Pick disease

Niemann-Pick disease is a group of genetic disorders belonging to the larger family of metabolic disorders called 'lysosomal storage diseases', in which fats build up within lysosomes (parts of the body's cells that break down nutrients and other materials). This affects the way cells work and causes them to die, affecting normal functioning of tissues and organs, including the liver, spleen and brain.

There are three types of Niemann-Pick disease (A, B and C), with different genetic causes and different symptoms, which may include behavioural problems, learning disabilities and difficulty moving and speaking.

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

At the time of designation, Niemann-Pick disease affected approximately 0.1 in 10,000 people in the European Union (EU). This was equivalent to a total of 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. This represents a population of 515,700,000 (Eurostat 2017).

At the time of designation, Zavesca (miglustat) was authorised in the EU to treat Niemann-Pick disease, type C. Zavesca was used to treat the neurological symptoms of the disease (symptoms affecting the brain and nerves).

The sponsor has provided sufficient information to show that ursodeoxycholic acid might be of significant benefit for patients with Niemann-Pick disease because early data in patients indicated that the medicine may improve liver function. This assumption will need to be confirmed at the time of marketing authorisation, in order to maintain the orphan status.

Ursodeoxycholic acid is known to reduce the content of cholesterol in the liver, but the exact mechanism through which it may work in Niemann-Pick disease is not clearly understood. Preliminary data show it may improve liver function as well as neurological symptoms (affecting the brain).

The effects of ursodeoxycholic acid have been evaluated in experimental models.

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

At the time of submission, ursodeoxycholic acid was authorised in the EU for the treatment of gallstones and liver diseases such as primary biliary cirrhosis.

At the time of submission, ursodeoxycholic acid was not authorised anywhere in the EU for Niemann-Pick disease or designated as an orphan medicinal product elsewhere for this condition.

In accordance with Regulation (EC) No 141/2000 of 16 December 1999, the COMP adopted a positive opinion on 11 April 2017 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.