Investigational small molecules in phase II clinical trials for the treatment of epilepsy: cannabidivarin, selurampanel (BGG492) and ganaxolone.

Epilepsy is a neurological disorder that significantly impacts the quality of life of the affected person and affects approximately 70 million people globally. Despite advances in research, nearly a third of patients have refractory or pharmacoresistant epilepsy. Even though numerous antiepileptic drugs (AEDs) have been approved over the past decade, there are no agents that halt the development of epilepsy. Thus, new and improved AEDs to prevent refractory seizures and modify the disease are necessary. Areas covered: We highlight recent advances and emerging trends in new and innovative drugs for epilepsy and seizure disorders. We review three small molecule drugs in phase II clinical trials: Cannabidivarin, BGG492 (Selurampanel) and Ganaloxone. Expert opinion: The full potential of Cannabidivarine will be realised by testing in other types of treatment-resistant seizures while the identification of ‘superselective’ AMPAR antagonists that target only calcium-permeable receptors will be a challenge; their specific mechanisms however, will be attractive for partnering with drugs that have complementary mechanisms in polytherapy. Moreover, there is a new interest surrounding Ganaloxone because of a new submicron formulation that improves its absorption and pharmacokinetic profile; the analysis of new phase II studies in patients with refractory focal seizures is necessary before progressing. Further clinical and preclinical innovations will define the future for these small molecule-type drugs in epilepsy therapeutics.