EU/3/16/1651

On 28 April 2016, orphan designation (EU/3/16/1651) was granted by the European Commission to Voisin Consulting S.A.R.L., France, for recombinant adeno-associated viral vector serotype 9 carrying the gene for the human E6-AP ubiquitin protein ligase for the treatment of Angelman syndrome.

What is Angelman syndrome?

Angelman syndrome is an inherited disorder that mainly affects the brain. It is caused by an abnormality in the gene needed to make an enzyme called E6-AP ubiquitin ligase, which is essential for normal development of the brain. Children with this condition often have delayed development, intellectual disability, severe speech impairment, 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 and seizures.

What is the estimated number of patients affected by the condition?

At the time of designation, Angelman syndrome affected approximately 1 in 10,000 people in the European Union (EU). This was equivalent to a total of around 51,000 people*, and is below the ceiling for orphan designation, which is 5 people in 10,000. This isbased 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 513,700,000 (Eurostat 2016).

What treatments are available?

At the time of designation, no medicines were authorised in the EU for the treatment of Angelman syndrome. Available treatments were aimed at treating some of the symptoms of the disease such as medicines for epilepsy and behavioural therapy.

How is this medicine expected to work?

The medicine is made of a virus that has been modified to contain a working copy of the gene for E6‑AP ubiquitin ligase. After being given once to the patient as an injection into the space around the spine, the virus is expected to carry the gene into the brain cells, enabling them to produce the missing protein for a long period. This is expected to improve the symptoms of the disorder.

The virus used in this medicine (‘adeno-associated virus’) does not cause disease in humans.

What is the stage of development of this medicine?

At the time of submission of the application for orphan designation, the evaluation of the effects of the medicine in experimental models was ongoing.

At the time of submission, 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 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 of 16 December 1999, the COMP adopted a positive opinion on 23 March 2016 recommending the granting of this designation.

Opinions on orphan medicinal product designations are based on the following three criteria:

• 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.

The Committee for Orphan Medicinal Products reviews the orphan designation of a product if it is approved for marketing authorisation.