EU/3/20/2332 - orphan designation for treatment of KCNQ2 developmental and epileptic encephalopathy
retigabine
OrphanHuman
Overview
On 19 October 2020, orphan designation EU/3/20/2332 was granted by the European Commission to FGK Representative Service GmbH, Germany, for retigabine (also known as XEN496) for the treatment of KCNQ2 developmental and epileptic encephalopathy.
KCNQ2 developmental and epileptic encephalopathy is a severe form of epilepsy. It is caused by mutations (changes) in a gene required for the proper function of brain cells causing seizures (fits), which begin soon after birth. Although the seizures may improve in some children within months to years, these children continue to show signs of brain impairment with symptoms of abnormal muscle tone, stiffening of the limbs, visual problems, and problems with normal development.
KCNQ2 developmental and epileptic encephalopathy is a long-term debilitating condition, which is life-threatening due to the risk of sudden death in epilepsy.
At the time of designation, KCNQ2 developmental and epileptic encephalopathy affected approximately 0.1 in 10,000 people in the European Union (EU). This was equivalent to a total of around 5,000 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).
*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, Iceland, Liechtenstein, Norway and the United Kingdom. This represents a population of 519,200,000 (Eurostat 2020).
At the time of designation, treatment for the disease was focused on treating seizures with epilepsy medicines.
The sponsor has provided sufficient information to show that the medicine might be of significant benefit for patients with KCNQ2 developmental and epileptic encephalopathy because there have been documented cases of the medicine reducing the number of seizures in patients for whom other medicines did not work.
This assumption will need to be confirmed at the time of marketing authorisation, in order to maintain the orphan status.
Patients with the condition have mutations in the KCNQ2 gene responsible for the production of certain proteins (voltage-gated potassium channels) located on the nerve cells of the brain that control transmission of electrical impulses within the brain.
The medicine is expected to work by keeping the potassium channels open, allowing potassium to move in and out of the cells and maintaining normal electrical activity in the brain. This is expected to reduce epileptic seizures and improve the symptoms of the disease.
The effects of retigabine have been evaluated in experimental models.
At the time of submission of the application for orphan designation, no clinical trials with retigabine in patients with KCNQ2 developmental and epileptic encephalopathy had been started.
At the time of submission, retigabine was not authorised anywhere in the EU for the treatment of KCNQ2 developmental and epileptic encephalopathy. Orphan designation of retigabine had been granted in the United States for this condition.
In accordance with Regulation (EC) No 141/2000, the COMP adopted a positive opinion on 10 September 2020, 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.
Key facts
- Active substance
- retigabine
- Intended use
- Treatment of KCNQ2 developmental and epileptic encephalopathy
- Orphan designation status
- Positive
- EU designation number
- EU/3/20/2332
- Date of designation
- Sponsor
FGK Representative Service GmbH
Review of designation
The Committee for Orphan Medicinal Products reviews the orphan designation of a product if it is approved for marketing authorisation.
EMA list of opinions on orphan medicinal product designation
EMA publishes information on orphan medicinal product designation adopted by the Committee for Orphan Medicinal Products (COMP) on the IRIS online platform:
Patients' organisations
For contact details of patients’ organisations whose activities are targeted at rare diseases, see:
European Organisation for Rare Diseases (EURORDIS), a non-governmental alliance of patient organisations and individuals active in the field of rare diseases.
Orphanet, a database containing information on rare diseases, which includes a directory of patients’ organisations registered in Europe.
EU register of orphan medicines
The list of medicines that have received an orphan designation in the EU is available on the European Commission's website: