What is focal refractory epilepsy?

Focal epilepsy describes a group of disorders in which patients experience seizures that arise from a specific part of the brain.1

Epilepsy is considered to be refractory or pharmacoresistant when seizures persist despite trials of at least two tolerated and appropriately chosen antiseizure medicines.2

Focal refractory epilepsy:

a vast unmet need

Epilepsy is one of the most common neurological diseases, affecting over 50 million people worldwide, according to the World Health Organization.3 Approximately one in five patients with epilepsy has focal refractory epilepsy (FRE).

Currently, it is estimated that there are around 2 million prevalent patients with FRE in the United States, the United Kingdom and the European Union, combined.4

Refractory epilepsy is a devastating condition. The mortality in people with refractory epilepsy is four times higher than in the general population.5 In the United Kingdom alone, approximately 1,000 epilepsy-related deaths are recorded each year.6

The hallmark symptom of FRE is recurrent and unpredictable seizures, which can cause injury and become life-threatening. People with epilepsy often struggle with anxiety, depression, and the social stigma associated with their disease,7 and their professional life is severely restricted.

Inadequate treatment options

Antiseizure medicines

Despite the availability of many antiseizure medications, with over 30 different medicines approved to date, there is still a very large number of patients who have refractory epilepsy. The proportion of patients with refractory epilepsy has barely changed over the past three decades, and still represents approximately one third of the overall population with epilepsy.8,9

Among patients who have failed to respond satisfactorily to two anti-seizure medicines, the probability of achieving seizure freedom after one year with the addition of further medicines is less than 10.10

Furthermore, the chronic use of multiple antiseizure medicines is associated with significant safety and tolerability issues, including but not limited to: sedation, rash, coordination disturbances, psychiatric symptoms, including depression, reduced bone density, weight gain/loss, pregnancy risks (including birth defects, neurodevelopmental disorders and major congenital malformations), and drug-drug interactions.11

Surgical treatment options

According to the International League Against Epilepsy (ILAE), patients with FRE should be considered for surgery if they have failed two antiseizure medications. The two main surgical treatment options with the highest probability of achieving seizure freedom are resective surgery and laser ablation (or laser interstitial thermal therapy or LITT), with a probability of achieving seizure freedom at 50-76%12 and 58%,13 respectively, at one year.

However, both resective surgery and laser ablation involve the permanent destruction of cerebral tissue with a risk of long-term consequences including visual field defect, cognitive impairment and personality change, as well as acute risks of haemorrhage and infection.14 Giving patients’ aversion to the loss of cerebral tissue and surgical risks, epilepsy surgery has been significantly under-utilised in patients with FRE to date.

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