A Novel Approach to Assess the Impact of Disease in Patients with SCN8A-Related Developmental and Epileptic Encephalopathy (P3-9.008)

Abstract

<h3>Objective:</h3> Clinical data generated using Invitae’s Ciitizen patient-consented, real-world data platform were used to explore disease burden in <i>SCN8A</i>-DEE. <h3>Background:</h3> <i>SCN8A</i>-related DEE is a rare disease associated with pathogenic variants in the <i>SCN8A</i> gene encoding the voltage-gated sodium channel alpha subunit Na_v1.6. Due to significant phenotypic heterogeneity, comprehensive understanding of disease impact and progression is limited. <h3>Design/Methods:</h3> Real-world clinical data were extracted from patients with an <i>SCN8A</i> variant using the Ciitizen platform, which employs a proprietary approach combining machine learning and expert human review to streamline generation of research-grade data from unstructured health records spanning ~10 years. Extracted data including seizure history, comorbidities, and therapeutic interventions were analyzed. <h3>Results:</h3> 79 patients were enrolled and contributed data for analyses. Mean patient age was 8.2 years (1–23), with similar percentages of males and females. Patients were categorized based on age at seizure onset; ≤6 months (75.6%) or &gt;6 months (34.2%). A further group included patients without seizures (5%). Mean age at seizure onset was 70.4 days (1–175) for patients with early (≤6 months) seizures and 749.3 days (224–4409) for those with later (&gt;6 months) seizures. While seizure frequency was variable, most patients continued to experience seizures over time. Procedural interventions and hospitalizations were high across the lifespan; nearly a third occurring in the first year of life. Mean number of medications prescribed over a patient’s lifetime was 17.6 (3–44). Patients experienced multiple comorbidities; global developmental delay was the most common (81%), with sleep disorders, hypotonia, feeding difficulties and GERD reported in &gt;50%. <h3>Conclusions:</h3> This work represents a new generation of natural history study providing the most robust real-world dataset to date on disease burden and progression in <i>SCN8A</i>-DEE. Knowledge from this study is anticipated to accelerate drug development efforts by providing new insights into the broad, longitudinal impact of disease, therefore informing trial endpoints beyond seizure symptomatology. <b>Disclosure:</b> Kelley Dalby has received personal compensation for serving as an employee of Praxis Precision Medicines. Kelley Dalby has stock in Praxis Precision Medicines. Kelley Dalby has stock in RogCon. Mr. Snyder has received personal compensation for serving as an employee of Praxis Precision Medicines. Mr. Snyder has received stock or an ownership interest from Praxis Precision Medicines. Dr. G Matthews has received personal compensation in the range of $100,000-$499,999 for serving as a Consultant for Praxis Precision Medicines. Dr. G Matthews has stock in Praxis Precision Medicines. Dr. Oldham has received personal compensation for serving as an employee of Praxis Precision Medicines. Steven Petrou has received personal compensation in the range of $100,000-$499,999 for serving as a Consultant for Praxis Precision Medicines. Steven Petrou has stock in Praxis Precision Medicines. The institution of Steven Petrou has received research support from Praxis Precision Medicines. The institution of Steven Petrou has received research support from Medical Research Future Fund. Steven Petrou has received intellectual property interests from a discovery or technology relating to health care. Steven Petrou has received intellectual property interests from a discovery or technology relating to health care. Dr. Souza has received personal compensation for serving as an employee of Praxis Precision Medicines. Dr. Souza has stock in Praxis Precision Medicines.