EU/3/17/1855

Lennox-Gastaut syndrome is a severe form of epilepsy that starts in childhood between 2 and 5 years of age. Patients have different types of seizures (fits), including tonic seizures (muscle contraction lasting few seconds to minutes), atypical absence seizures (during which the person has a blank stare but is still partly aware of their surroundings) and drop seizures (brief loss of muscle tone and consciousness, causing abrupt falls). Most children with Lennox-Gastaut syndrome experience some degree of learning disability and developmental delay, along with behavioural problems such as hyperactivity and aggression.

Lennox-Gastaut syndrome is long-term debilitating due to the seizures, effects on mental function and behavioural problems.

At the time of designation, Lennox-Gastaut syndrome affected approximately 2 in 10,000 people in the European Union (EU). This was equivalent to a total of around 103,000 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 515,700,000 (Eurostat 2017).

At the time of designation, several epilepsy medicines were authorised in the EU for treatment of seizures in children with Lennox-Gastaut syndrome, including clonazepam, felbamate, lamotrigine, rufinamide, and topiramate.

The sponsor has provided sufficient information to show that cannabidiol might be of significant benefit for patients with Lennox-Gastaut syndrome. Results from studies in patients showed that cannabidiol reduced the number of seizures in patients in whom previous treatment failed. 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 targets that 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 seizures are caused by excessive electrical activity in the brain, altering the movement of calcium is expected to reduce or prevent the seizures in Lennox-Gastaut syndrome. Cannabidiol is also thought to act on adenosine, a chemical messenger in the brain that plays an important role in suppressing seizures.

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 Lennox-Gastaut syndrome were ongoing.

At the time of submission, cannabidiol was not authorised anywhere in the EU for Lennox-Gastaut syndrome. Orphan designation of cannabidiol 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 16 February 2017 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.