Senior Clinical Scientist Xenon Pharmaceuticals Inc.
Rationale: SCN8A developmental and epileptic encephalopathy (SCN8A-DEE) is a rare and severe genetic epilepsy syndrome characterized by early onset developmental delay, cognitive impairment and intractable seizures. Variants in the SCN8A gene have also been reported in patients with a broad phenotypic spectrum and varying degrees of severity. This online caregiver survey, solicited by an advocacy group (The Cute Syndrome Foundation) via an online questionnaire, was conducted to better understand variability in the clinical presentation of SCN8A-DEE and SCN8A-related epilepsy. Methods: A 36-question online survey was developed to obtain de-identified data from caregivers of children with SCN8A-DEE or SCN8A-related epilepsy. The survey included items such as genetic diagnosis, seizure severity and type, current and prior anti-seizure medication use, and best/worst seizure medications per caregiver perception. All results were based on available responses and analyzed descriptively. Results: One hundred twenty-five survey responses were received. Based on these responses, most patients were two to < 12 years of age, and 117 (94%) patients experienced some type of seizure. The most common seizure type at the time of survey was generalized tonic-clonic, followed by partial/focal, absence, and myoclonic. In addition to seizures, the most common comorbid conditions in patients were intellectual disability (73%) and hypotonia (58%). Nine patients (8%) experiencing seizures were not currently receiving any anti-seizure treatment for SCN8A-DEE or SCN8A-related epilepsy, although 99 (85%) had tried and stopped one or more previous treatment. The most common weaned treatments were levetiracetam (50%), topiramate (32%), clonazepam (31%), and clobazam (26%). Levetiracetam was rated by caregivers as the medication with worst seizure control. Conclusions: Results from this caregiver survey showed that patients with SCN8A-DEE or SCN8A-related epilepsy had high seizure burden, multiple neurologic/motor comorbidities, and insufficient treatment. The patients in this study who previously tried and stopped various medications indicated general dissatisfaction with current treatment options and suggested ongoing unmet therapeutic needs in this heterogeneous patient population. Funding: Please list any funding that was received in support of this abstract.: The Cute Syndrome Foundation received funds from Xenon for this patient survey and other projects/events. The Shay Emma Hammer Foundation and the University of Arizona received funds from Xenon for an SCN8A patient registry but not directly for this patient survey.