EU/3/18/1993: Orphan designation for the treatment of neuronal ceroid lipofuscinosis

Neuronal ceroid lipofuscinosis is a group of inherited diseases where substances known as lipofuscins made of fats and proteins build up in the brain and other parts of the body, such as the eye. Symptoms of the disease include delayed speech, inability to coordinate muscle movements, fits, loss of vision and mental disability.

Neuronal ceroid lipofuscinosis is a debilitating and life-threatening condition that leads to death by early adulthood.

At the time of designation, neuronal ceroid lipofuscinosis affected approximately 0.5 in 10,000 people in the European Union (EU). This was equivalent to a total of around 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 517,400,000 (Eurostat 2018).

At the time of designation, the medicine Brineura was authorised in the EU for the treatment of neuronal ceroid lipofuscinosis type 2. Brineura replaces the TPP1 protein missing in this form of the disease and it is given by infusion (drip) directly into the brain. The disease was also managed by treating its symptoms.

The sponsor has provided sufficient information to show that the medicine might be of significant benefit for patients with neuronal ceroid lipofuscinosis because laboratory data show improvements in survival and movement skills. The medicine would be given by mouth, which is an advantage over the currently authorised medicine.

This assumption will need to be confirmed at the time of marketing authorisation, in order to maintain the orphan status.

Gemfibrozil is expected to work in several ways, including by increasing production and activity of TPP1 (the protein lacking in patients with neuronal ceroid lipofuscinosis type 2), by increasing production of lysosomes (part of the body's cells that break down nutrients and other materials), and by preventing cell death and inflammation. These activities are together expected to improve the outcome of patients affected by the condition.

The effects of gemfibrozil have been evaluated in experimental models.

At the time of submission of the application for orphan designation, no clinical trials with gemfibrozil in patients with neuronal ceroid lipofuscinosis had been started.

Gemfibrozil is authorised in several EU countries to help lower the level of fats in the blood.

At the time of submission, gemfibrozil was not authorised anywhere in the EU for neuronal ceroid lipofuscinosis. Orphan designation of the medicine had been granted in the US for neuronal ceroid lipofuscinoses.

In accordance with Regulation (EC) No 141/2000 of 16 December 1999, the COMP adopted a positive opinion on 15 February 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.