The US Early Access Program for fenfluramine allowed access to the treatment for patients who were ineligible for clinical trials.
Data from the US Early Access Program (EAP) of fenfluramine (FFA; Fintepla; Zogenix), a prospective, open-label study presented at the American Epilepsy Society (AES) Annual Meeting, December 4–8, 2020, show that FFA is well-tolerated and provides a significant clinical benefit to adults with Dravet Syndrome (DS) as well as children.1
These findings were presented by M. Scott Perry, MD, medical director of neurology, and co-director, Jane and John Justin Neurosciences Center; Medical Director, Genetic Epilepsy Clinic, Cook Children’s Medical Center, who stated that “due to enrollment criteria in the clinical trials requiring DS patients to be ≤18 years old, data for adult DS patients are limited. This analysis presents data for both adult and pediatric patients with DS who participated in a US EAP for [FFA].”
The EAP allowed pre-approval access to FFA for patients with DS who were ineligible for ongoing clinical trials, such as adults ≥18 years of age. During the study, FFA was added to each patient’s anticonvulsant drug regimen at 0.2 mg/kg/day 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, and a maximum of 26 mg/day. If patients were also treated with stiripentol the maximum dose was 0.4 mg/kg/day, to a maximum of 17 mg/day.
At each study visit, the treating physician assessed patients by cognitive function, behavior, motor ability, and Global Clinical Impression of Improvement (CGI-I) as compared to baseline on a 7-point Likert scale that ranged from 1, or “very much improved,” to 4, or “no change,” and to 7, or “very much worse.”
Of the 109 patients with DS that enrolled in the EAP, 19 were ≥18 years old with a mean age of 22.5 years (range, 18.5–32). Sixty-eight percent (n = 13) of the adult group were female. In the child cohort, the mean age was 8.0 years (range, 1.0–17.8) and 48% (n = 47) were female. The median duration of treatment was 90 days (range, 30–540 days) and was similar in patients <18 years old (105 days) and ≥18 years old (90 days). Of those in the child cohort, 6.4% (n = 7) withdrew due to reasons such as lack of efficacy and patient decision.
As of the first study visit after 30 days of treatment, 74% of adult and pediatric patients improved on CGI-I. In addition to CGI-I, 32% to 42% of adults and 41% to 60% of children were reported to have improvements in cognitive function, behavior, and motor function.
A total of 29 patients, 3 of which were ≥18 years old, reported decreased or low appetite, and 6 pediatric patients reported weight loss. No deaths, valvular heart disease, or pulmonary hypertension occurred.
“Overall improvement in patient CGI-I ratings was comparable in adults and children treated with FFA... FFA was generally well-tolerated by both adults and children; no cases of valvular heart disease or pulmonary arterial hypertension were observed,” Perry concluded.
Other findings concerning FFA also presented at AES include new data from an open-label extension trial, known as Study 1503 (NCT02823145), of fenfluramine (Fintepla; Zogenix), that suggest the treatment continued to provide both durable and significant reductions in monthly convulsive seizure frequency for patients with Dravet syndrome who were treated for up to 3 years.2
In Study 1503, 38.2% of the patients experienced a ≥75% reduction and 63.4% of patients reported a ≥50% reduction in monthly convulsive seizure frequency over the course of the entire analysis period. At least 1 dose of FFA was administered to 330 patients who enrolled (mean age, 9.0 years [±4.6]), with a median treatment duration of 631 days (range, 7–1086). A total of 282 patients reported >12 months of exposure to fenfluramine and 128 patients reported >24 months in the OLE.