Abstract Details

Title Efficacy of Soticlestat Treatment by Seizure Type in Patients with Dravet Syndrome or Lennox–Gastaut Syndrome in a Phase 2, Randomized, Placebo-controlled Study (ELEKTRA)

Topic Epilepsy/Clinical Neurophysiology (EEG)

Presentation(s) P11 - Poster Session 11 (11:45 AM-12:45 PM)

Poster/Presentation
Number 9-002

Background

DS and LGS involve developmental delay and frequent epileptic activity. The published ELEKTRA study investigated efficacy and safety of soticlestat, a cholesterol 24-hydroxylase inhibitor, in children with DS or LGS. Primary endpoint was change in convulsive (DS) and drop (LGS) seizure frequencies.

Objective

To develop a post hoc analysis of soticlestat treatment efficacy by seizure type in patients with Dravet syndrome (DS) or Lennox–Gastaut syndrome (LGS) in ELEKTRA (NCT03650452), a phase 2, randomized, placebo-controlled study of adjunctive soticlestat (≤300 mg BID, weight-adjusted) in children aged 2–17 years with DS demonstrating ≥3 convulsive seizures/28 days, or with LGS demonstrating ≥4 drop seizures/28 days at baseline.

Design/Methods

Post hoc efficacy analyses determined percent change in seizure frequency from baseline, by seizure type. Patients’ caregivers recorded seizure number and type throughout the baseline and full (20-week) treatment periods, including generalized tonic–clonic, focal to bilateral tonic–clonic, focal with motor signs and atonic seizures.

Results

Of 141 enrolled patients, 126 (89%) completed ELEKTRA. The modified intent-to-treat population received ≥1 doses of study drug and had ≥1 efficacy assessments (DS, n=51; LGS, n=88). Median seizure frequency changes from baseline in patients with DS receiving soticlestat (placebo): generalized tonic–clonic seizures, −27.2% [n=14] (19.5%, n=21); focal to bilateral tonic–clonic seizures, −73.9% [n=9] (8.4%, n=4). Median seizure frequency changes from baseline in patients with LGS receiving soticlestat (placebo): generalized tonic–clonic seizures, −33.4% [n=17] (−20.0%, n=11); focal seizures with motor signs, −64.3% [n=10] (−21.1%, n=7); atonic seizures, −33.9% [n=16] (−17.9%; n=13); focal to bilateral tonic–clonic seizures, −41.3% [n=6] (none observed).

Conclusions

Reduced median frequency of specific seizure types was observed in patients receiving soticlestat as adjunctive therapy. Investigation of soticlestat adjunctive therapy for these seizure types in other epilepsies is warranted (phase 3 studies ongoing for DS and LGS).

Study funded by Takeda Pharmaceutical Company Limited.

Authors/Disclosures
Naga V. Pathi Jagannatham, MD (Takeda Pharmaceuticals) PRESENTER	Dr. Pathi Jagannatham has received personal compensation for serving as an employee of Takeda Pharmaceuticals. Dr. Pathi Jagannatham has received personal compensation for serving as an employee of GlaxoSmithKline. Dr. Pathi Jagannatham has stock in Takeda Pharmaceuticals. Dr. Pathi Jagannatham has stock in GlaxoSmithKline.
Dennis J. Dlugos, MD	Dr. Dlugos has received research support from NIH. The institution of Dr. Dlugos has received research support from The Epilepsy Study Consortium.
Yasir P. Khan, MD (Takeda)	No disclosure on file
	No disclosure on file
Arturo I. Benitez, MD (Takeda)	Dr. Benitez has received personal compensation for serving as an employee of Takeda.
Mahnaz Asgharnejad, PharmD (Takeda Pharmaceuticals)	Mahnaz Asgharnejad, PharmD has received personal compensation for serving as an employee of Takeda Pharmaceuticals. Mahnaz Asgharnejad, PharmD has stock in GlaxoSmithKline. Mahnaz Asgharnejad, PharmD has stock in Takeda Pharmaceuticals.