Understanding refractory epilepsies

Epileptic syndrome is a chronic non-communicable condition of the brain. It is characterized by seizures caused by a synchronized and abnormal excitation of a fairly extensive group of neurons in the cerebral cortex, which can spread to other areas of the brain or cause them to malfunction.

Key figures

10%

Up to 10% of the world’s population will experience at least one seizure in their lifetime1¹.

50 million

Around 50 million people worldwide have epilepsy, making it one of the most common neurological conditions ¹.

70%

70% of people with epilepsy can be seizure-free if their condition is properly diagnosed and managed ¹.

The risk of premature death is up to three times higher in people with epilepsy than in the general population. Many deaths are potentially preventable (falls, drowning, etc.)¹.

Epileptic syndrome: a complex and heterogeneous pathology

Five main causes of epileptic seizures have been identified to date: structural, genetic, infectious, metabolic and immune. However, in about 50% of epilepsy cases worldwide¹, the cause of this syndrome remains unknown.

Epileptic seizures take extremely varied forms: convulsions, but also loss of consciousness, memory loss, behavioral disorders, etc. The symptoms associated with the seizure depend on the area or areas of the brain impacted by the excessive electric discharges.

The frequency, duration, and intensity of seizures vary considerably from patient to patient and from seizure to seizure. Some people with epileptic syndrome will experience only a few seizures in their lifetime, while others may experience them several times a day.

Epilepsies: multiple pathologies

Currently, the term “epilepsy” has been replaced by “epileptic syndrome” or “epilepsies”. This new terminology aims to better reflect the heterogeneous and complex nature of this pathology. In 2017, the International League Against Epilepsy (ILAE) defined a new classification of seizures². It reflects the wide variety of causes and symptoms of epileptic syndrome as well as the many scientific advances made since the previous classification in 1989.

Epileptic seizures are now classified according to the area of the brain where they start, their possible impact on the affected person’s level of consciousness, and the presence of other symptoms such as convulsions. This new classification also introduces different levels of diagnosis: seizure type, epilepsy type (focal, generalized, combined generalized and focal, unknown) and epileptic syndrome. The causes of seizures should be investigated at each stage of the diagnosis to ensure the best care for the patient. In a context where more than 30 drug molecules³ are currently available, the control of a patient’s epileptic seizures requires a personalized approach and treatment, adapted to their biological characteristics and the nature of their seizures.

Refractory epilepsies: a third of patients are waiting for new therapeutic solutions

Epileptic syndrome is considered refractory – or drug-resistant – when seizures persist despite administration of two appropriate drug treatments over a period of one year. About one third of people with epilepsy are in this situation⁴. Most refractory epilepsies have a genetic cause. Refractory epilepsies often appear in childhood.

Did you know?

One third of people with epilepsy are affected by a drug-resistant form.

Patients affected by a drug-resistant form of epilepsy currently have recourse to a limited number of therapeutic options, including:

Surgery to remove the epileptogenic area. However, this procedure can only be done if the epileptogenic area is focal, unique, and sufficiently far from highly functional brain regions (movement, speech, etc.). Surgery is therefore only a satisfactory therapeutic response for a minority of patients. Globally, about 10 million patients are eligible for surgery out of about 50 million people with epilepsy⁵.
Neuromodulation through vagus nerve stimulation, responsive stimulation or deep brain stimulation. This is a palliative approach that can lead to a reduction in the number of seizures and a reduction in their intensity and therefore an improvement in the quality of life of the patient. However, it very rarely makes it possible to completely eliminate seizures and is therefore only a partial therapeutic solution.

Significant work has been carried out by the scientific community in recent years to better understand the neurobiological mechanisms of epileptic syndrome and to decipher its causes. This has led to the emergence of innovative therapeutic approaches. These include gene therapies⁶ or RNA modulation therapies. These therapies pave the way for a molecular approach to the treatment of epileptic syndrome. They can act on genetic mutations responsible for epileptic seizures or modulate the activity of neuronal circuits. Clinical studies for the treatment of temporal lobe epilepsy – the majority of which is drug-resistant – with gene therapy started in 2024⁷. Recent scientific advances around RNA therapies demonstrate particularly promising results, especially in the treatment of neonatal epilepsy of genetic origin – developmental and epileptic encephalopathies – one of the main causes of which is the presence of pathogenic variants in the KCNQ2 gene, for example⁸.

Testimonial

“The tremendous progress we have made in understanding the genetics of the epilepsy syndromes over the past few years paves the way for innovative treatments, such as RNA modulation therapies and gene therapies. The ability to target specific mutations offers new hope for personalized and more effective treatments, especially for patients living with refractory epilepsy.”

Javier Avendaño MD, Clinical Development Director, Neurology Therapeutic Area

Improving the quality of life of patients with epilepsy

The research carried out in recent years meets a twofold objective: to identify therapeutic solutions for refractory epilepsy and to improve the quality of life for patients living with a drug-sensitive epileptic syndrome and that of their caregivers. The research world and the pharmaceutical industry are particularly focused on reducing the adverse side effects associated with treatments. Listening to and taking into account patient feedback is now an integral part of the process of developing new therapeutic drug approaches.

About Servier

Servier is committed to the development of new therapeutic approaches for refractory epilepsy, in particular epileptic and developmental encephalopathies. We are currently conducting several preclinical studies to explore new therapeutic solutions.

Alongside patients, we are also continuing our efforts to improve the quality of life of patients living with epileptic syndrome, as well as that of their loved ones.

Sources

[1] Organisation mondiale de la Santé – Epilepsie, https://www.who.int/fr/news-room/fact-sheets/detail/epilepsy – page consulted on 03/12/25
[2] Epilepsy society – ILAE new seizure classification, https://epilepsysociety.org.uk/blog/ilae-new-seizure-classification – page consulted on 03/12/25
[3] Fondation Française pour la Recherche sur l’Epilepsie – Comprendre l’épilepsie – Les traitements, https://www.fondation-epilepsie.fr/comprendre-epilepsie/les-traitements/ – page consulted on 03/12/25
[4] International League Against Epilepsy – Drug-Resistant Epilepsy, https://www.ilae.org/patient-care/drug-resistant-epilepsy – page consulted on 03/12/25
[5 ] National Library of Medicine – Samanta D, Ostendorf AP, Willis E, Singh R, Gedela S, Arya R, Scott Perry M. Underutilization of epilepsy surgery: Part I: A scoping review of barriers. Epilepsy Behav. 2021 Apr;117:107837. doi: 10.1016/j.yebeh.2021.107837. Epub 2021 Feb 18. PMID: 33610461; PMCID: PMC8035287 – https://pmc.ncbi.nlm.nih.gov/articles/PMC8035287/#R2.
[6] INSERM – Épilepsie résistante aux médicaments : l’espoir d’une thérapie génique, https://www.inserm.fr/actualite/epilepsie-resistante-aux-medicaments-lespoir-dune-therapie-genique/ – page consulted on 03/12/25
[7 ]CNRS – Un espoir de thérapie génique pour traiter l’épilepsie pharmacorésistante, https://www.cnrsinnovation.com/actualite/un-espoir-de-therapie-genique-pour-traiter-lepilepsie-pharmacoresistante/ – page consulted on 03/12/25
[8 ] Agence nationale de la recherche – Le Projet IMprove : vers de nouvelles perspectives thérapeutiques pour les épilepsies néonatales génétiques incurables, https://anr.fr/en/latest-news/read/news/le-projet-improve-vers-de-nouvelles-perspectives-therapeutiques-pour-les-epilepsies-neonatales-gen/ – page consulted on 03/12/25

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