Investigational small molecules in phase II clinical trials for the treatment of epilepsy

Expert Opin Investig Drugs. 2018 Dec;27(12):971-979. doi: 10.1080/13543784.2018.1543398. Epub 2018 Nov 13.

Abstract

Introduction: Epilepsy is a neurological disorder that significantly impacts the quality of life of affected persons. 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 these conditions are necessary.

Areas covered: We highlight recent advances in new and innovative drugs for epilepsy disorders. We review three small molecule drugs in phase II clinical trials: Cannabidivarin, BGG492 (Selurampanel) and Ganaloxone.

Expert opinion: The full potential of Cannabidivarin will be realized by testing in other types of treatment-resistant seizures; if they are beneficial, larger phase III clinical trials would probably be undertaken in the same patient population. About BGG492, the challenge will be to find 'superselective' AMPAR antagonists targeting only calcium-permeable receptors, with specific mechanisms, that may be attractive partners for drugs in polytherapy. Moreover, there is anew interest surrounding Ganaloxone because of a new submicron formulation that improves its absorption and pharmacokinetic profile, but new studies are necessary before progressing. Further clinical innovations will define the future for these small molecule-type drugs in epilepsy therapeutics.

Keywords: AED; Epilepsy; antiepileptic drugs; cannabidivarin; ganaxolone; seizures; selurampanel.

Publication types

  • Review

MeSH terms

  • Animals
  • Anticonvulsants / pharmacology
  • Anticonvulsants / therapeutic use*
  • Cannabinoids / pharmacology
  • Cannabinoids / therapeutic use
  • Clinical Trials, Phase II as Topic
  • Drug Design
  • Drug Resistant Epilepsy / drug therapy
  • Drug Resistant Epilepsy / physiopathology
  • Drugs, Investigational / pharmacology
  • Drugs, Investigational / therapeutic use*
  • Epilepsy / drug therapy*
  • Epilepsy / physiopathology
  • Humans
  • Pregnanolone / analogs & derivatives
  • Pregnanolone / pharmacology
  • Pregnanolone / therapeutic use
  • Quality of Life
  • Quinazolinones / pharmacology
  • Quinazolinones / therapeutic use

Substances

  • Anticonvulsants
  • Cannabinoids
  • Drugs, Investigational
  • Quinazolinones
  • selurampanel
  • ganaxolone
  • Pregnanolone
  • cannabidivarin