Soticlestat for drug-resistant epilepsy: Current evidence and clinical perspectives.

Epilepsy, particularly drug-resistant epilepsy, remains a significant clinical challenge, with many patients failing to achieve seizure control through conventional antiseizure medications. This unmet need has directed research toward alternative therapeutic targets, including neurosteroid modulation and novel molecular pathways. Soticlestat, a selective inhibitor of cholesterol 24-hydroxylase, is a mechanistically distinct investigational approach to epilepsy treatment by modulating mechanisms beyond those targeted by traditional antiseizure medication. Early-phase clinical trials and preclinical studies demonstrated soticlestat's potential in reducing seizure frequency and highlighted additional benefits related to quality-of-life improvements in epilepsy patients. However, recent Phase III trials in Dravet syndrome and Lennox-Gastaut syndrome reported mixed results. Beyond seizure control, soticlestat mechanism of action may offer neuroprotective effects, potentially addressing neurodegeneration and neuroinflammation associated with chronic epilepsy, which could support improved cognitive outcomes over time. These findings underscore the need for further research to elucidate the long-term benefits and potential synergy of soticlestat in combination with other antiseizure medications across diverse epilepsy syndromes. While challenges remain, soticlestat offers a promising therapeutic avenue for improving outcomes in DRE and warrants continued investigation as a potential adjunctive treatment.