Abstracts

Rationale:
Randomized, controlled studies of FINTEPLA (fenfluramine, FFA) in the treatment of Dravet syndrome (DS) have demonstrated profound reduction in seizure frequency with significantly prolonged seizure-free intervals. These studies enrolled patients ≤ 18 years old, making data in adult DS patients limited.
Method:
The Early Access Program (EAP) was initiated to allow pre-approval access to FFA for patients with DS who were not eligible to participate in ongoing clinical trials. In this prospective, open-label study, FFA was added to each eligible patient’s anticonvulsant drug regimen at 0.2 mg/kg/day given in 2 equivalent doses 12 hours apart. After 14 days, the dose could be titrated in 0.2 mg/kg/day steps based on effect and tolerability to a maximum dose of 0.7 mg/kg/day (maximum 26 mg/day) in patients not treated with stiripentol, or 0.4 mg/kg/day (maximum 17 mg/day) in patients also receiving stiripentol. At each study visit, the domains of cognitive function, behavior, motor ability, and Global Clinical Impression of Improvement (CGI-I) were assessed as compared to the pretreatment period for each patient by the treating physician, who used a 7-point Likert scale that ranged from 1 “very much improved” to 4 “no change” to 7 “very much worse.”
Results:
A total of 109 DS patients, 19 of whom were ≥ 18 years old, have enrolled in the EAP and had ≥ 1 effectiveness assessment. In the adult group, mean age was 22.5 years (range 18.5 to 32.0 years) and 13 (68%) patients were female. In the child cohort, mean age was 8.0 years (range 1.0 to 17.8 years) and 47 (48%) were female. The median duration of treatment was 90 days (range 30 to 540 days) and was similar in patients < 18 years old (105 days) and ≥ 18 years old (90 days). Seven children (6.4%) withdrew from the study (lack of efficacy, n=6; physician decision, n=1). Improvements in each domain were evident in each age cohort at the first study visit (30 days); 74% of patients (both adults and children) were noted to be improved on CGI-I. In addition to CGI-I, 32%-42% of adults and 41%-60% of children were reported to have improvements in cognitive function, behavior, and motor function (Table). A total of 29 patients, including 3 adults, reported decreased or low appetite, whereas 6 patients (all < 18 years old) reported weight loss. No deaths occurred. No valvular heart disease or pulmonary hypertension was observed.
Conclusion:
Results from this real-world Early Access Program experience with FFA used for DS suggest that adults with DS experience clinical benefit and tolerability comparable to children and adolescents during treatment with FFA.
Funding:
:Zogenix, Inc.