Authors :
Presenting Author: Joseph Sullivan, MD – UCSF
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, PhD – CogState; Javier Avendaño, MD – Stoke Therapeutics; Charlene Brathwaite, BA – Stoke Therapeutics; Carrie Condon, BA – Stoke Therapeutics; Dana Fitzpatrick, BS – Stoke Therapeutics; Fei Wang, PhD – Stoke Therapeutics; James Stutely, BS – Stoke Therapeutics; Kimberly Parkerson, MD – Stoke Therapeutics; Barry Ticho, MD – Stoke Therapeutics
Rationale:
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. This study evaluates SF as well as neurodevelopment, adaptive function, gait performance, and executive function in patients with DS over 24 months. Methods:
BUTTERFLY is the largest and longest longitudinal study of DS to date. It is a multicenter, longitudinal study in the US of 36 patients aged 2-18 years with genetically confirmed DS whose seizures are not controlled by their current antiseizure medications. Twenty-one patients (58.3%) completed the study and the last patient in the study completed their final 24-month visit on November 11, 2022. Eight patients who did not complete the study transferred to the Phase 1/2 study MONARCH (NCT04442295).
Results:
Patients enrolled equally across age groups: 2-7, 8-12, and 13-18 years; 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). SF was variable with no clear trends. Four patients were free of convulsive seizures during at least one 4-week period over the 24-month study. Based on observed data, both Bayley-III developmental quotient and Vineland-III composite showed trends towards small decreases in scores over 24 months. There was little change in mean total scores on the Gillette Functional Assessment Questionnaire over 24 months. Behavior Rating Inventory of Executive Function – Preschool index scores showed variability but trends towards decreasing (improved) scores at Month 18 (n=15) and Month 24 (n=15). 86.2% patients (n=29) at Month 12 and 78.9% patients (n=19) at Month 24 experienced no change to slight change on the Clinical Global Impression of Change Scale evaluating cognition. Conclusions:
Overall, data suggests most patients in BUTTERFLY continue to experience convulsive seizures over 24 months and neurodevelopmental gaps persist between patients with DS and neurotypical children. Data suggest these assessments may be useful for DS clinical studies. BUTTERFLY provides valuable insights on seizure and non-seizure manifestations in patients with DS.
Funding: Stoke Therapeutics