Soticlestat Reduces Seizure Frequency in Children With Dravet Syndrome

Cecil Hahn, MD, MPH

Data from the phase 2, multicenter, randomized, placebo-controlled, double-blind, parallel-group ELEKTRA study (NCT03650452) suggest that soticlestat (Ovid Therapeutics) treatment resulted in statistically significant reductions in seizure frequency from baseline in children with Dravet syndrome (DS).¹

These data were presented by Cecil Hahn, MD, MPH, child neurologist, The Hospital for Sick Children, and associate professor of pediatrics, University of Toronto, and colleagues at the American Epilepsy Society (AES) Virtual Meeting, December 4–8, 2020. Hahn and colleagues wrote that “in this phase 2 study, soticlestat treatment resulted in a statistically significant reduction in median seizure frequency compared to baseline in children with DS, and in a directional reduction in seizure frequency in patients with [Lennox-Gastuat syndrome; LGS] and was generally well-tolerated.”

ELEKTRA studied children aged 2-17 years with DS with greater or equal to 3 convulsive seizures per month as well as children with LGS with greater or equal to 4 drop seizures per month at baseline. The study consisted of a 4- to 6-week screening period followed by a 20-week treatment period consisting of an 8-week dose period and a 12-week maintenance period. Participants received up to 600 mg per day of soticlestat or placebo twice daily.

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Hahn and colleagues enrolled 141 participants, 126 of which completed the study. The modified intent to treat population included 239 participants, 51 with DS and 88 with LGS. These patients received at least 1 dose of soticlestat or placebo and had at least 1 efficacy assessment over the treatment period. 

Patients with either DS or LGS treated with soticlestat demonstrated a median 30.5% placebo-adjusted reduction in seizure frequency during the maintenance period (P = .0007; n = 120). A 25.1% placebo-adjusted reduction in seizure frequency was seen over the full treatment period (P = .0024; n = 139).

Patients with DS treated with soticlestat experienced a 33.8% median reduction in convulsive seizure frequency as compared to a 7.0% median increase in patients that received placebo, yielding a 46.0% median placebo-adjusted seizure reduction (P = .0007). Patients with LGS treated with soticlestat experienced a 20.6% median reduction in drop seizure frequency as compared to a 6.0% median reduction in patients that received placebo, yielding a 14.8% median placebo-adjusted reduction in seizure frequency (P = .128).

Treatment emergent adverse events (TEAEs) were experienced by 80.3% of patients treated with soticlestat and 74.3% of patients treated with placebo, demonstrating an apparent well-tolerance of soticlestat. Serious TEAEs were reported by 15.5% of patients in the soticlestat group and 18.6% of patients in placebo. No deaths occurred and the most frequently reported TEAEs in patients treated with soticlestat were lethargy and constipation.

We previously reported that ELEKTRA had met its primary end points in August 2020. Hahn previously said in a statement on ELEKTRA that “children with developmental epileptic encephalopathies like DS and LGS need more options to manage their treatment-resistant seizures. The results of the ELEKTRA study are very promising, particularly for children with DS and represent a clinically significant reduction in seizure burden. Moreover, soticlestat was well-tolerated in this study."²

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REFERENCES

1. Hahn C, Jiang Y, Villanueva V, et al. Efficacy, safety and tolerability of soticlestat (TAK-935/OV935) as adjunctive therapy in pediatric patients with Dravet syndrome and Lennox Gastaut syndrome (ELEKTRA). Presented at AES 2020 Virtual Meting; December 4–8, 2020; Abstract 851
2. Phase 2 ELEKTRA Study of Soticlestat (TAK-935/OV935) Meets Primary Endpoint Reducing Seizure Frequency in Children with Dravet Syndrome or Lennox-Gastaut Syndrome. News release. Ovid Therapeutics. Published online AUgust 25, 2020. Access February 5, 2021. https://investors.ovidrx.com/news-releases/news-release-details/phase-2-elektra-study-soticlestat-tak-935ov935-meets-primary