EU/3/01/056: 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 less than 0.5 in 10,000 people in the European Union (EU). This was equivalent to a total of fewer than 26,000 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 513,700,000 (Eurostat 2016).

At the time of designation, Zavesca (miglustat) was authorised in the EU to treat Niemann-Pick disease type C but no products had been authorised for Niemann-Pick disease types A and B.

The sponsor has provided sufficient information to show that the medicine 'recombinant human acid sphingomyelinase' might be of significant benefit for patients with Niemann-Pick disease types A and B because it is expected to be used to replace the enzyme that does not work well in these patients. Data in patients with Niemann-Pick disease type B showed that treatment with this medicine led to a decrease in liver and spleen volumes as well as improved lung function. This assumption will need to be confirmed at the time of marketing authorisation, in order to maintain the orphan status.

Because of a genetic mutation, patients with Niemann-Pick disease type A and B lack a functioning enzyme, acid sphingomyelinase, which is found in lysosomes and is needed to break down certain fats.

This medicine is a copy of the normal acid sphingomyelinase enzyme which is expected to replace the patients' faulty enzyme, and thereby reduce the build-up of fats within lysosomes and relieve some of the symptoms of the disease. It is not, however, expected to reduce brain damage as the medicine is unable to cross the blood-brain barrier which separates the blood from brain tissue.

The acid sphingomyelinase enzyme is produced by a method known as 'recombinant DNA technology': it is made by cells into which a gene (DNA) has been introduced, that makes them able to produce the enzyme.

The effects of the medicine have been evaluated in experimental models.

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

At the time of orphan designation, this medicine was not authorised anywhere in the EU for Niemann-Pick disease.

This medicine had been designed orphan on 19 September 2001 for the treatment of Niemann-Pick disease, type B. At the request of the sponsor and having assessed the additional data submitted, the COMP adopted a positive opinion on 17 October 2016 recommending the orphan condition be changed to Niemann-Pick disease.

Orphan designation of the medicine has been granted in the United States for acid sphingomyelinase deficiency.

• 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.