Current and future pharmacotherapy options for drug-resistant epilepsy

ABSTRACT

Introduction

Epilepsy is a common neurological condition, affecting over 70 million individuals worldwide.

Areas covered

The present paper reviews current and future (under preclinical and clinical development) pharmacotherapy options for the treatment of drug-resistant focal and generalized epilepsies.

Expert opinion

Current pharmacotherapy options for drug-resistant epilepsy include perampanel, brivaracetam and the newly approved cenobamate for focal epilepsies; cannabidiol (Epidiolex) for Lennox-Gastaut Syndrome (LGS), Dravet and Tuberous Sclerosis Complex (TSC); fenfluramine for Dravet syndrome and ganaxolone for seizures in Cyclin-dependent kinase-like 5 (CDKL5) deficiency disorder. Many compounds are under clinical development and may hold promise for future pharmacotherapies. For adult focal epilepsies, padsevonil and carisbamate are at a more advanced Phase III stage of clinical development followed by compounds at Phase II like selurampanel, XEN1101 and JNJ-40411813. For specific epilepsy syndromes, XEN 496 is under Phase III development for potassium voltage-gated channel subfamily Q member 2 developmental and epileptic encephalopathy (KCNQ2-DEE), carisbamate is under Phase III development for LGS and Ganaxolone under Phase III development for TSC. Finally, in preclinical models several molecular targets including inhibition of glycolysis, neuroinflammation and sodium channel inhibition have been identified in animal models although further data in animal and later human studies are needed.

KEYWORDS:

• Epilepsy
• antiepileptic drugs
• cenobamate
• fenfluramine
• ganaxolone
• carisbamate
• padsevonil

Article highlights

• We present current and future pharmacotherapy options for the treatment of drug-resistant epilepsy that have emerged over the last 10 years.

• Current options for focal epilepsy include perampanel, brivaracetam and cenobamate.

• Current options for specific epilepsy syndromes include cannabidiol for LGS, Dravet and TSC, fenfluramine for Dravet and Ganaxolone for CDKL5 deficiency disorder.

• Several compounds are in development including carisbamate, selurampanel, XEN1101 and JNJ-40411813.

• Emerging molecular targets in preclinical models include effects on glycolysis, neuroinflammation and sodium channels.

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Disclosure statement

MM has received speaker fees from Eisai and UCB, consultancy fees from MEDSCAPE, Angelini, Bial and Elsevier, and royalties from Elsevier and Springer. MM receives honorarium as Editor-in-Chief of Epilepsy & Behavior. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

SE is funded by a Clinical Research Training Fellowship awarded by the Association of British Neurologists and Patrick Berthoud Charitable Trust.