Twelve-month Analysis of BUTTERFLY: An Observational Study to Investigate Cognition and Other Non-seizure Comorbidities in Children and Adolescents with Dravet Syndrome (DS)
Abstract number :
Submission category :
4. Clinical Epilepsy / 4C. Clinical Treatments
Submission ID :
Presentation date :
12/3/2022 12:00:00 PM
Published date :
Nov 22, 2022, 05:24 AM
Joseph Sullivan, MD – University of California San Francisco; Elaine Wirrell, MD – Mayo Clinic; Kelly Knupp, MD – Children's Hospital Colorado; Muhammad Zafar, MD – Duke University; Robert Flamini, MD – PANDA Neurology; Dillion Chen, MD – UCSD; Pam Ventola, NA – CogState; Charlene Brathwaite, NA – Stoke Therapeutics; Carrie Condon, NA – Stoke Therapeutics; James Stutely, NA – Stoke Therapeutics; Nancy Wyant, NA – Stoke Therapeutics; Javier Avendaño, MD – Stoke Therapeutics; Kimberly Parkerson, MD – Stoke Therapeutics; Barry Ticho, MD, PhD – Stoke Therapeutics
Rationale: Dravet syndrome (DS) is a severe and progressive genetic developmental and epileptic encephalopathy that typically begins in the first year of life. It is characterized by high seizure frequency (SF) and severity, intellectual disability, ataxia/motor abnormalities, and a high risk of sudden unexplained death. There remains a need for therapies to reduce SF and improve non-seizure comorbidities. There is a lack of prospective long-term data regarding the progression of substantial non-seizure comorbidities in patients with DS. This fully enrolled study evaluates neurodevelopment, adaptive function, gait performance, executive function, as well as SF in patients with DS.
Methods: BUTTERFLY is an ongoing, multicenter, longitudinal, prospective study in the U.S. of 36 patients aged 2 to 18 yrs with genetically confirmed DS whose seizures are not controlled by their current antiepileptic drugs. Primary endpoints assess neurodevelopment and adaptive function over 24 months. Data cut off was March 7, 2022, after all patients completed their month 12 visit.
Results: Patients enrolled equally across 3 age groups: 2 to 7 yrs, 8 to 12 yrs, and 13 to 18 yrs; 61% were female, 94% were white, and 14% were Latino. Across all patients, mean age of seizure onset was 5.1 months (range, 2-12 months; n=36). There was a median change of 7.63% (95% confidence interval (CI): -36.84 to 42.59%, n=17) in total convulsive SF from baseline to month 12. Three patients were free of convulsive seizures during the 4-week baseline and/or 12-month follow-up. Bayley-III (BSID) developmental quotient (DQ) mean change across all groups was -1 (95% CI: -3 to 1, p=0.17) from baseline to month 12. Vineland-III (VABS) adaptive behavior composite (ABC) mean change across all groups was -1.63 (95% CI: -4.15 to 0.89, p=0.20) from baseline to month 12. Gillette Functional Assessment Questionnaire (FAQ) total mean score at baseline across all groups was 32.7 (SD=13.12, n=34) with a mean change of -0.6 (SD=5.69, n=27) from baseline to month 12. Behavior Rating Inventory of Executive Function – Preschool (BRIEF-P) global executive composite mean score at baseline across all groups was 128.8 (SD=26.40, n=35) with a mean change of 0.6 (SD=16.12, n=26) from baseline to month 12.
Conclusions: Data suggest neurodevelopment, adaptive function, gait performance, and executive function remain relatively stable over 12 months in children and adolescents with DS enrolled in the BUTTERFLY study. These data suggest these scales may be useful for clinical studies in DS. This long-term prospective study will provide valuable insights on the course of seizure and non-seizure manifestations in patients with DS.
Funding: Stoke Therapeutics