EU/3/17/1836 - orphan designation for treatment of Lennox-Gastaut syndrome

Fenfluramine hydrochloride

Overview

 

On 27 February 2017, orphan designation (EU/3/17/1836) was granted by the European Commission to Zogenix International Limited, United Kingdom, for fenfluramine hydrochloride for the treatment of Lennox-Gastaut syndrome.

Fenfluramine hydrochloride treatment of Lennox-Gastaut syndrome has been authorised in the EU as Fintepla since 24 January 2023.

What is 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.

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

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 isbased on the information provided by the sponsor and the knowledge of the Committee for Orphan Medicinal Products (COMP).

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*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).

What treatments are available?

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.

How is this medicine expected to work?

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.

What is the stage of development of this medicine?

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.

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.

EU/3/17/1836: Public summary of opinion on orphan designation: Fenfluramine hydrochloride for the treatment of Lennox-Gastaut syndrome

AdoptedReference Number: EMA/71973/2017

Key facts

• Active substance:
  Fenfluramine hydrochloride
• Medicine name:
  Fintepla
• Intended use:
  Treatment of Lennox-Gastaut syndrome
• Orphan designation status:
  Positive
• EU designation number:
  EU/3/17/1836
• Date of designation:
  27/02/2017
• Sponsor:

  UCB Pharma;

Review of designation

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

The Committee for Orphan Medicinal Products reviewed the orphan designation of Fintepla at the time of change to the terms of the marketing authorisation, and confirmed that the orphan designation should be maintained. 

More information is available in the Fintepla : EPAR - Orphan maintenance assessment report (II-0012).