Initial findings of the ENDYMION trial (NCT03635073) suggest soticlestat (OV935/TAK935; Ovid Therapeutics, New York, NY) reduces the frequency of seizures in people with rare developmental and epileptic encephalopathies (DEE), including Dravet’s syndrome, Lennox-Gastaut syndrome (LGS), and other medically refractory epilepsies.
Median seizure frequency reductions were 84% after 25-36 weeks of treatment (n=6) and 90% following 37-48 weeks (n=4) of treatment. Also, the longest seizure-free durations experienced by 2 different patients were 264 consecutive days and 150 consecutive days. At 12 weeks soticlestat continued to have a favorable safety and tolerability profile.
ENDYMION is a prospective, open-label extension study in 7 adult participants with DEE who previously completed a 12-week phase 1b/2a clinical trial of soticlestat. The mechanism of action for soticlestat is thought to be inhibition of the enzyme cholesterol 24-hydroxylase (CH24H), which is a positive allosteric modulation of the N-methyl-D-aspartate (NMDA) glutamate receptor.
“While this first data cut includes a small number of patients, these initial results from ENDYMION reaffirm the potential of soticlestat to provide a tangible and durable clinical benefit for patients with DEE, a group of difficult-to-treat seizure disorders with limited therapeutic options,” said Amit Rakhit, MD, MBA, chief medical officer and head of research and development, Ovid. “Specifically, we believe the sustained and progressively improving median seizure reduction up to 90% seen in these patients is encouraging and, while early, compares favorably to other studies in different types of DEE.”
Lila T. Worden, MD, and Shavonne L. Massey, MD, MSCE
James Geyer, MD, and Paul Cox