EU/3/18/2034: Orphan designation for the treatment of neurodegeneration with brain iron accumulation

Neurodegeneration with brain iron accumulation describes a group of inherited diseases characterised by a build-up of iron in the part of the brain involved in movement.

The diseases lead to brain damage and symptoms including progressive dystonia (worsening painful muscle spasms), spasticity (muscle stiffness), effects similar to Parkinson's disease such as shaking, muscle stiffness and slow movement, mental disorders including dementia, optic atrophy (damage to nerves in the eye) and retinal degeneration (damage to the back of the eye).

Neurodegeneration with brain iron accumulation is debilitating and life threatening because it results in reduced ability to walk, worsening vision and reduced life expectancy.

At the time of designation, neurodegeneration with brain iron accumulation affected approximately 0.03 in 10,000 people in the European Union (EU). This was equivalent to a total of around 2,000 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).

No satisfactory methods of treatment for neurodegeneration with brain iron accumulation were authorised in the EU at the time of orphan designation. Patients received supportive therapy including medicines for muscle problems and movement disorders to deal with the symptoms.

Deferiprone is an iron chelator. This means that it attaches to iron in the body to form a compound that can be eliminated by the body, mainly in the urine. Deferiprone is expected to travel to the brain and reduce the build-up of iron in brain cells. This is expected to improve the symptoms in patients with neurodegeneration with brain iron accumulation.

The effects of deferiprone have been evaluated in experimental models.

At the time of submission of the application for orphan designation, clinical trials with deferiprone in patients with neurodegeneration with brain iron accumulation were ongoing.

At the time of submission, deferiprone was authorised throughout the EU for treatment of iron overload in patients with thalassaemia major.

At the time of submission, deferiprone was not authorised anywhere in the EU for neurodegeneration with brain iron accumulation. Orphan designation of the medicine has been granted in the United States for treatment of this condition.

In accordance with Regulation (EC) No 141/2000 of 16 December 1999, the COMP adopted a positive opinion on 24 May 2018 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.