Soticlestat in Dravet syndrome and Lennox-Gastaut Syndrome (LGS)
Dravet syndrome and Lennox-Gastaut syndrome are types of developmental and epileptic encephalopathies (DEEs), a heterogeneous group of rare epilepsy syndromes. Dravet syndrome is caused by a genetic mutation in the SCN1A gene. Researchers believe this mutation can lead to excess production of glutamate, an excitatory neurotransmitter, that in turn leads to seizures. LGS is a heterogeneous condition and characterized by several different types of seizures, most commonly atonic (drop), tonic and atypical absence seizures.
Soticlestat restores appropriate glutamate levels by targeting the CH24H pathway, thereby increasing the health of the central nervous system (CNS) and reducing inflammation. We believe soticlestat has the potential to reduce seizure susceptibility and improve seizure control and may provide benefit where other mechanisms of conventional anti-epileptic drugs have not.
Studies of soticlestat in animal models suggest the drug may:
⦁ Significantly reduce seizure burden
⦁ Reduce glutamate excitotoxicity
⦁ Improve cognitive function
⦁ Improve survival
⦁ Provide protection from seizure-related mortality
Ovid Therapeutics designed and conducted a robust clinical program for individuals with developmental and epileptic encephalopathies (DEE). A Phase 1b/2a study was completed and positive results were released. Additionally, Ovid completed the Phase 2 ELEKTRA study in individuals with Lennox-Gastaut syndrome or Dravet syndrome and positive topline results have been reported.
Further development and research of soticlestat will be led by our partner Takeda, including Phase 3 studies in children and adults with Dravet syndrome and Lennox-Gastaut syndrome scheduled to begin in 2021. Additionally, the ongoing open-label ENDYMION extension study will continue under direction from our partner Takeda.
References: 1. Nishi T et al. Poster presented at: SfN 2018. 2. Hasegawa S et al. Poster presented at: SfN 2018. 3. Nishi T et al. Poster presented at: AES 2017. Abstract 2.260. 4. Hawkins NA et al. Oral presentation at: AES 2018. Abstract1.286.