Ovid Therapeutics recently presented updates on their clinical trials of soticlestat (TAK-935/OV935) at the American Academy of Neurology virtual meeting for their adult DEE cohorts.
Soticlestat targets the cholesterol pathway by inhibiting the enzyme CH24H (cholesterol 24-hydroxylase), which produces 24HC (24-hydroxycholesterol). When there is too much 24HC in the brain, it can over-activate glutamate signaling which increases neuronal excitability and can lead to seizures. Soticlestat showed pre-clinical efficacy for seizure control, and the emerging clinical trial data is promising. The most recent updates are regarding adult DEE groups, and show both short-term (<3 months, Phase 1b/2a study) and extended (6-12 months currently with a goal of ~2 years, termed the “ENDYMION” study) safety and efficacy of Soticlestat for treatment of seizures. Median seizure frequencies decreased by 40-60% in short-term and 80-90% in the extended study. Reported side effects were mild to moderate, but there was a potential interaction between Soticlestat and perampanel which may exacerbate seizures. While the sample sizes are small (n=13-16 for the short-term study and n=7 for the extended study), the researchers are encouraged by the efficacy in reducing seizure activity despite the heterogeneity (multiple causes) of DEE. Currently, Phase 2 trials for soticlestat are underway in pediatric patients with Dravet syndrome and Lennox-Gastaut syndrome (the “ELEKTRA” study) and researchers are hopeful for similar outcomes to DEE study groups.
Links to the presentations can be found here.