EU/3/19/2197

Neuronal ceroid lipofuscinosis is a group of inherited diseases where deposits known as lipofuscins made of fats and proteins build up in the brain and other parts of the body, such as the eye, causing damage. 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 0.2 in 10,000 people in the European Union (EU). This was equivalent to a total of around 10,000 people¹, 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).

¹Disclaimer: 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 518,400,000 (Eurostat 2019).

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 enzyme (one of several proteins whose absence can lead to lipofuscin build-up) which is missing in this form of the disease. 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 that it may allow treatment of patients with neuronal ceroid lipofuscinosis type 6, which involves a different protein, and for whom no treatment exists. This assumption will need to be confirmed at the time of marketing authorisation, in order to maintain the orphan status.

This medicine is expected to be used in patients with neuronal ceroid lipofuscinosis type 6. These patients have mutations (changes) in a gene called CLN6 that is responsible for the production of a protein needed for the function of the endoplasmic reticulum (ER), a structure in the cell involved in various processes including the breakdown of harmful substances. As a result, the ER does not work properly, leading to build-up of lipofuscins.

This medicine is made of a virus that contains normal copies of the CLN6 gene. When injected into the patient, it is expected that the virus will be carried into the nerve cells enabling them to start producing a working CLN6 protein. This is expected to restore the function of the ER and relieve the symptoms of the disease.

The type of virus used in this medicine ('adeno-associated virus') does not cause disease in humans.

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 neuronal ceroid lipofuscinosis were ongoing.

At the time of submission, recombinant self-complementary adeno-associated viral vector serotype 9 containing the human CLN6 gene was not authorised anywhere in the EU for the treatment of neuronal ceroid lipofuscinosis or designated as an orphan medicinal product elsewhere for this condition.

In accordance with Regulation (EC) No 141/2000, the COMP adopted a positive opinion on 18 July 2019, 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.