Final safety data from an open-label study presented at AES 2025 supported long-term fenfluramine use in pediatric and adult patients with Dravet syndrome or Lennox-Gastaut syndrome.
Final results from a combined open-label extension (OLE) study (NCT03936777) indicated that long-term treatment with fenfluramine (Fintepla; UCB) in pediatric and adult patients with Dravet syndrome (DS) or Lennox-Gastaut syndrome (LGS) was safe and consistent with prior studies. The data, presented at the recently concluded
Among 412 participants in the OLE study (DS, n = 265; LGS, n = 147), the median duration of fenfluramine treatment was 729.5 days (range, 8–1544). Although the treatment discontinuation rate was higher in patients with LGS (29.9%) than in patients with DS (3.0%), researchers reported that the fenfluramine exposure was greater in the LGS cohort compared with the DS cohort. Across all study cohorts, investigators observed that the median overall fenfluramine exposure was 1464.5 days (range, 171–2800).
Fenfluramine is
The study enrolled patients who previously participated in fenfluramine open-label studies of DS (NCT02823145),4 LGS (NCT03355209),5 or DS/LGS (NCT03467113) and who were receiving at least 1 concomitant antiseizure medication at the time. Researchers noted that patients continued their final fenfluramine dose from the prior study, with flexible titration as clinically indicated, up to a maximum of 0.7 mg/kg/d (26 mg/d) without concomitant stiripentol or 0.4 mg/kg/d (17 mg/d) with stiripentol.
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All told, the mean age of participants was 14.1 years (SD, 6.8); 69.2% were aged 2 to 17 years and 30.8% were aged 18 years or older. Among patients with DS and LGS, 27.2% (72 of 265) and 37.4% (55 of 147), respectively, were adults. Coming into the OLE, the primary objective was to assess the long-term safety and tolerability of fenfluramine. Secondary objectives included evaluation of patient global functioning using Clinical Global Impression–Improvement (CGI–I) ratings reported by caregivers and investigators at the last visit compared with the OLE study baseline. Post hoc analyses were also conducted by age group and to estimate overall fenfluramine exposure.
At least 1 treatment-emergent adverse event (TEAE) was reported in 311 patients (75.5%), while fenfluramine-related serious TEAEs, as assessed by investigators, occurred in 5 patients (1.2%). Notably, 3 deaths were reported and were deemed unrelated to fenfluramine. Rates of TEAEs and serious TEAEs were lower in patients with DS than those with LGS and no cases of clinically confirmed valvular heart disease or pulmonary arterial hypertension were observed. Overall, the safety findings were consistent with the known fenfluramine safety profile, with no new or unexpected safety signals identified.
At the last study visit, 251 of 258 patients with DS (97.3%) were rated by both caregivers and investigators as improved or unchanged on the CGI–I scale compared with the open-label extension baseline. Among patients with LGS (n = 143), 122 (85.3%) and 125 (87.4%) were rated as improved or unchanged by caregivers and investigators, respectively. These CGI–I findings suggested sustained clinical benefit with a median overall fenfluramine exposure of 4 years. Collectively, the safety and results global functioning support long-term fenfluramine use in pediatric and adult patients with DS or LGS.
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