Long‐Term Soticlestat Treatment in Patients with Developmental and/or Epileptic Encephalopathies in the ENDYMION Ongoing Open‐Label Extension Study
Cecil D. Hahn1, Yuwa Jiang2, Vincente Villanueva3, Marta Zolnowska4, Dimitrios Arkilo5, Peter B. Forgacs6, Mahnaz Asgharnejad5, Ying Yan6, Dennis Dlugos7
1The Hospital for Sick Children, 2Pediatrics, Peking University First Hospital, 3Refractory Epilepsy Unit, Hospital Universitario y Politécnico La Fe, 4Plejady Medical Center, 5Takeda Pharmaceutical Company Limited, 6Ovid Therapeutics Inc, 7Neurology, The Children’s Hospital of Philadelphia
Objective:

To report interim safety and efficacy outcomes following ≤9 months of soticlestat (TAK-935/OV935) as adjunctive therapy in patients with developmental and epileptic encephalopathies (DEEs) in ENDYMION (NCT03635073).

Background:

DEEs typically start in childhood with treatment-resistant seizures, and are associated with progressive cognitive decline. In phase 2 studies, soticlestat was associated with reductions in seizure frequency in patients with Dravet syndrome (DS), Lennox-Gastaut syndrome (LGS) and CDKL5 deficiency disorder.

Design/Methods:

ENDYMION is a phase 2, multicenter, open-label extension study of soticlestat (≤600 mg/day; mg/kg dosing for <60 kg body weight) in pediatric and adult patients with DEEs who completed a previous soticlestat clinical study, or received treatment for ≥10 weeks. ENDYMION comprises a dose-optimization period, a maintenance period of <5 years, and a 4-week safety follow-up period. Safety endpoints include incidence of treatment-emergent adverse events (TEAEs) and efficacy endpoints include change from baseline in seizure frequency.

 

Results:

At the time of analysis, 83 of 116 patients (71.6%) with DEEs experienced ≥1 TEAE (mild, n=71 [61.2%]; moderate, n=31 [26.7%]; severe, n=8 [6.9%]). Twelve patients (10.3%) experienced ≥1 serious TEAE; none were considered to be drug-related. TEAEs occuring in ≥5% of patients were constipation, diarrhea, decreased appetite, insomnia, nasopharyngitis, pyrexia, seizure, somnolence, and upper respiratory tract infection. Six patients (5.2%) discontinued due to TEAEs.

At weeks 1–12, 13–24, 25–36, median changes in seizure frequency from baseline (of antecedent study) in DS patients were –36.11% (n=36), –48.45% (n=31), and –20.35% (n=14), respectively, and in LGS patients were –30.00% (n=57), –12.12% (n=48) and –21.64% (n=28), respectively.

Conclusions:

Interim results from ENDYMION suggest long-term administration of soticlestat is generally well-tolerated in the study population, with a safety profile consistent with findings from previous studies. Soticlestat reduced seizure frequency in patients with DEEs in this study population.

Study funded by Takeda Pharmaceutical Company Limited and Ovid Therapeutics Inc.