EU/3/19/2148: Orphan designation for the treatment of Friedreich’s ataxia

Friedreich’s ataxia is an inherited disease that causes a range of symptoms that worsen over time, including difficulty walking, inability to co-ordinate movements, muscle weakness, speech problems, damage to the heart muscle and diabetes.

Patients with Friedreich’s ataxia do not have enough frataxin, a protein that regulates iron in mitochondria (energy-producing components of cells). As a result, iron builds up within the cells, which in turn results in the production of toxic forms of oxygen that damage cells in the brain, the spinal cord and nerves, as well as in the heart and pancreas.

Friedreich’s ataxia is a debilitating and life-threatening disease because of the worsening of symptoms over time. The disease is usually fatal in early adulthood.

At the time of designation, Friedreich’s ataxia 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 518,400,000 (Eurostat 2019).

At the time of designation, no satisfactory methods were authorised in the EU for the treatment of Friedreich’s ataxia. Different treatments were used to relieve the symptoms of the disease, such as medicines for diabetes and heart problems. Patients were also offered walking aids to allow them to remain as independent as possible, and other devices to assist them with everyday tasks such as eating and taking care of themselves. Speech therapy and physiotherapy were also used.

The medicine works by blocking an enzyme called D-amino acid oxidase (DAAO), which leads to increased levels of a substance known as D-serine in various organs and tissues, in particular in the brain. In the brain, D-serine is thought to play a key role in controlling muscle activity. By increasing the levels of D-serine, the medicine is expected to improve coordination of movements.

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 Friedreich’s ataxia were ongoing.

At the time of submission, the medicine was not authorised anywhere in the EU for Friedreich’s ataxia. Orphan designation of the medicine had been granted in the United States for this condition.

In accordance with Regulation (EC) No 141/2000 of 16 December 1999, the COMP adopted a positive opinion on 21 February 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.