Novel antiseizure medications in the development pipeline: promising candidates and recent failures

In the past decade, we have observed a paradigm shift in the discovery of novel antiseizure medications (ASMs), which is a consequence of significant progress in epilepsy genetics, the availability of novel disease models, drug-screening technologies, the discovery of new mechanisms of action, expanding existing drugs into new populations, or new routes of delivery. This resulted in a very rich pipeline of potential future treatments for epilepsy, including gene-modifying treatments for rare genetic epilepsies and mechanistically guided precision treatments. Hopes are high that this pipeline may bring therapeutic breakthroughs similar to those recently achieved with cenobamate for the common drug-resistant focal epilepsy and fenfluramine for seizures in Dravet syndrome. Furthermore, we stand at the beginning of a new era of epilepsy treatment expansion, from traditional seizure suppression to disease prevention and modification. This review discusses the most advanced and promising candidates in the clinical development pipeline but also describes recent failures in the development of novel ASMs.