EU/3/13/1219

Dravet syndrome, also called severe myoclonic epilepsy of infancy (SMEI), is a severe form of epilepsy that affects children and adults. It is caused by defects in genes required for the proper function of brain cells.

In Dravet syndrome, the seizures (fits) begin in the first year of life, and are most often associated with a high temperature (febrile convulsions). Later, other types of seizures typically occur, including status epilepticus (a state of continuous seizure requiring emergency medical care). From the second year of life, the child's development begins to decline or reverse, leading to problems such as impaired mental and motor (movement) skills.

Dravet syndrome is debilitating in the long term because of the poor development of mental and motor skills. It is also life threatening particularly because of the occurrence of major seizures.

At the time of designation, Dravet syndrome affected less than 0.5 in 10,000 people in the European Union (EU). This was equivalent to a total of fewer than 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 512,200,000 (Eurostat 2013).

At the time of designation, the medicine Diacomit (stiripentol) was authorised in the EU as add-on treatment for generalised tonic-clonic seizures (major fits, including loss of consciousness) in children with Dravet syndrome.

The sponsor has provided sufficient information to show that fenfluramine hydrochloride might be of significant benefit for patients with Dravet syndrome because it works in a different way to existing treatments and early studies show that it might improve the outcome of patients when used as add-on to other treatments. This assumption will need to be confirmed at the time of marketing authorisation, in order to maintain the orphan status.

Although the way fenfluramine hydrochloride works is not clearly understood, this medicine is expected to increase the levels of the neurotransmitter serotonin in the brain. This may have a role in preventing the seizures in Dravet syndrome and fenfluramine hydrochloride has been shown to reduce seizures in experimental models.

The effects of fenfluramine hydrochloride have been evaluated in experimental models.

At the time of submission of the application for orphan designation, no clinical trials with fenfluramine hydrochloride in patients with Dravet syndrome were ongoing.
Fenfluramine hydrochloride had been previously authorised in several countries worldwide as an appetite suppressant for the treatment of obesity. The medicine was withdrawn from the EU market in 1997.

At the time of submission, fenfluramine hydrochloride was not authorised anywhere in the EU for Dravet syndrome or designated as an orphan medicinal product elsewhere for this condition.

In accordance with Regulation (EC) No 141/2000 of 16 December 1999, the COMP adopted a positive opinion on 6 November 2013 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.