Abstracts

Rationale: Ezogabine is an anti-seizure medication with a unique mechanism of action as a KCNQ/Kv7 potassium channel opener.  We hypothesize that it may be particularly beneficial for patients with KCNQ2 encephalopathy and that side effects are tolerable. Methods: Eight patients with variants in KCNQ2 and phenotype of KCNQ2 encephalopathy who were treated with ezogabine were enrolled in our IRB approved protocol, Genetics of Epilepsy and Related Disorders, at Boston Children’s Hospital. Seven patients had pathogenic or likely pathogenic KCNQ2 variants and one patient had two variants of uncertain significance in KCNQ2 thought to explain her phenotype. Recruitment was facilitated through the KCNQ2 Cure Alliance Foundation, and patients were treated at several medical centers in the United States.  Data was collected by review of medical records and structured interviews with families. Results: Eight patients (6 males, 2 females) with KCNQ2 encephalopathy were treated with ezogabine, starting at a median of 8 months (range 7 weeks and 2.5 years) and continuing for a median of 2.6 years (range 7 months to 4.5 years). Treatment is ongoing in all patients, however 7/8 began weaning of ezogabine due to the announcement that manufacturing would be discontinued in the near future.  Seven of 8 patients had seizure onset in the first week of life and one patient had seizure onset at 5 months of age.  Patients had multiple seizures types with tonic and tonic-clonic being the most commonly reported. Seizure frequency at onset was multiple daily in all patients at onset and EEG patterns were variable. At the time of starting ezogabine, 4 patients had daily seizures, 2 patients had weekly seizures, 1 patient had seizures 50%) within 1-2 weeks, and sustained improved seizure frequency over time in 5/6.  Developmental improvements were also notably reported in all 8 patients. Specifically families reported improved alertness, vocalizations, and motor skills. The only adverse reaction reported was urinary retention in 3 patients. Upon weaning, 3 of 7 patients had increased seizure frequency, 2 of 7 had worsened agitation/irritability, 1 of 7 had poor sleep, 2 of 7 had developmental regression while 1 of 7 had improved alertness and muscle tone, and 2/7 had no major changes. Conclusions: Data from this initial observational study suggests that ezogabine is effective and tolerable in patients with KCNQ2 encephalopathy. It may help not only seizure control but also developmental outcomes. Consideration of controlled trials in this targeted population is warranted. Funding: None