EU/3/17/1836: Orphan designation for the treatment of Lennox-Gastaut syndrome

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 delays, 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 patients with Lennox-Gastaut syndrome, including clonazepam, felbamate, lamotrigine, nitrazepam, rufinamide, sodium valproate and topiramate.

The sponsor has provided sufficient information to show that fenfluramine hydrochloride might be of significant benefit for patients with Lennox-Gastaut syndrome. Preliminary data showed that adding fenfluramine hydrochloride to previous treatment reduced the number of seizures in patients in whom previous treatment alone was not sufficient. This assumption will need to be confirmed at the time of marketing authorisation, in order to maintain the orphan status.

Epilepsy is caused by excessive electrical activity in the brain. The exact way in which fenfluramine hydrochloride works is still unclear but it seems to stimulate certain receptors in the brain that are involved in the release of the chemical messenger serotonin from nerve cells. By increasing serotonin levels, fenfluramine is thought to help stabilise electrical activity in the brain and prevent seizures.

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

At the time of submission of the application for orphan designation, a clinical trial with fenfluramine hydrochloride in patients with Lennox-Gastaut syndrome was ongoing.

At the time of submission, fenfluramine hydrochloride was not authorised anywhere in the EU for Lennox-Gastaut syndrome or designated as an orphan medicinal product elsewhere for this condition. Orphan designation has been granted in the EU for Dravet syndrome, another form of epilepsy.

In accordance with Regulation (EC) No 141/2000 of 16 December 1999, the COMP adopted a positive opinion on 19 January 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.