EU/3/14/1339: Orphan designation for the treatment of Dravet syndrome

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 511,100,000 (Eurostat 2014).

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 cannabidiol might be of significant benefit for patients with Dravet syndrome because early studies show that it could reduce the number of fits in patients with this condition when used together with existing treatments. This assumption will need to be confirmed at the time of marketing authorisation, in order to maintain the orphan status.

Cannabidiol is a substance extracted from the Cannabis sativa plant. Although the way this medicine works is not clearly understood, cannabidiol is thought to act on a 'channel' protein called VDAC1 found on the mitochondria, the energy producing components inside cells. These channels play a role in the movement of calcium in the cells, which in turn is important for the transmission of electrical signals in some nerve cells. As fits are caused by excessive electrical activity in the brain, altering the action of VDAC1 is expected to reduce or prevent the fits in Dravet syndrome.

The effects of cannabidiol have been evaluated in experimental models.

At the time of submission of the application for orphan designation, clinical trials with cannabidiol in patients with Dravet syndrome were planned.

At the time of submission, cannabidiol was not authorised anywhere in the EU for Dravet 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 4 September 2014 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.