EU/3/16/1786: Orphan designation for the treatment of aromatic L-amino acid decarboxylase deficiency

Aromatic L-amino acid decarboxylase deficiency is an inherited condition affecting the nervous system. It is caused by lack of the enzyme aromatic L-amino acid decarboxylase (AADC), which is needed to produce certain substances vital for the normal function of the brain and nerves, including dopamine, and serotonin. Symptoms appear in the first year of life and include rigidity or muscle floppiness, spasms and abnormal movements, swallowing difficulties, abnormal eyeball movements, poor sleep, developmental delay and behavioural problems.

Aromatic L-amino acid decarboxylase deficiency is a long-term debilitating and life-threatening condition because it can lead to multiple organ failure.

At the time of designation, aromatic L-amino acid decarboxylase deficiency affected less than 0.01 in 10,000 people in the European Union (EU). This was equivalent to a total of fewer than 500 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 513,700,000 (Eurostat 2016).

At the time of designation no satisfactory method was authorised in the EU for the treatment of aromatic L-amino acid decarboxylase deficiency. Patients were mainly offered supportive treatment to manage symptoms.

Aromatic L-amino acid decarboxylase deficiency is caused by mutations (changes) in the gene that produces the AADC enzyme. The medicine consists of a virus that contains a functional version of the AADC gene. When given to the patient, it is expected that the virus will carry the AADC gene into nerve cells, enabling them to produce the missing enzyme. This in turn is expected to enable the cells to produce the substances they need to function properly (such as dopamine and serotonin), thus improving symptoms of the condition.

The virus used in this medicine (adeno-associated viral vector) 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 aromatic L-amino acid decarboxylase deficiency were ongoing.

At the time of submission, the medicine was not authorised anywhere in the EU for aromatic L-amino acid decarboxylase deficiency. Orphan designation of the medicine had been granted in the United States for the condition.

In accordance with Regulation (EC) No 141/2000 of 16 December 1999, the COMP adopted a positive opinion on 6 October 2016 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.