EU/3/20/2389: Orphan designation for the treatment of Angelman syndrome

Angelman syndrome is a genetic disorder that mainly affects the brain. It is caused by a change in the gene needed to make an enzyme called E3 ubiquitin ligase (UBE3A), which is essential for normal brain development. Children with this condition often have delayed development, intellectual disability, severe speech defects, problems with movement and balance, recurrent seizures (fits) and sociable behaviour with frequent smiling.

Angelman syndrome is a long-term debilitating condition due to the developmental delay, problems with movement, sleep disorders and seizures.

At the time of designation, Angelman syndrome affected less than 1 in 10,000 people in the European Union (EU). This was equivalent to a total of fewer than 52,000 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).

*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, Iceland, Liechtenstein, Norway and the United Kingdom. This represents a population of 519,200,000 (Eurostat 2020).

At the time of designation, no medicines were authorised in the EU for the treatment of Angelman syndrome. Treatments were aimed at reducing symptoms of the disease such as epilepsy, sleep disorders and physical, behavioural and speech problems.

In patients with Angelman syndrome, lack of UBE3A means the communication connections (known as synapses) between nerve cells do not develop properly. The medicine is similar to a part of insulin-like growth factor (IGF-1), a substance in the body that is essential for synapse formation and brain development. The medicine controls IGF-1 levels and also prevents inflammation in the brain. These effects are expected to help the brain form new synapses and keep them working, thereby reducing some symptoms of the condition.

The effects of the medicine have been evaluated in experimental models.

At the time of submission of the application for orphan designation, no clinical trials with the medicine in patients with Angelman syndrome had been started.

At the time of submission, the medicine was not authorised anywhere in the EU for the treatment of Angelman syndrome. Orphan designation of the medicine had been granted in the United States for this condition.

In accordance with Regulation (EC) No 141/2000, the COMP adopted a positive opinion on 3 December 2020, 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.