Antiseizure Therapy Fenfluramine Continues to Show Pronounced Benefits in Rare, Developmental Epilepsies


One meta-analysis featuring 8 studies showed that more than half of patients reported a 100% reduction in their generalized tonic-clonic seizures or tonic-clonic seizures.

Orrin Devinsky, MD, director of NYU Langone’s Comprehensive Epilepsy Center

Orrin Devinsky, MD

At the recently concluded 35th international Epilepsy Congress (IEC), held September 2-6, in Dublin, Ireland, UCB Pharma presented several posters showcasing the clinical benefits of fenfluramine (Fintepla) across multiple forms of epilepsy, including rare epileptic disorders such as Dravet syndrome (DS), Lennox-Gastaut syndrome (LGS), and CDKL5 deficiency disorder.1

The first presentation was a review of 13 studies assessing the impact of the therapy on generalized tonic-clonic (GTCS) or tonic-clonic seizures (TCS) in a cohort (n = 561) of rare epilepsy syndromes. Most patients (70.6%) experienced GTCS or TCS at baseline, and fenfluramine was typically initiated at 0.2 mg/day and titrated per protocol or through physician discretion.

In 8 of the studies, including 4 randomized controlled trials, treatment with fenfluramine resulted in a median percent reduction in GTCS ranging from 45.7% to 90.8%. Among 8 studies providing data, 7 reported that at least half of the patients experienced reductions in GTCS or TCS of at least 75%. In addition, 5 studies reported more than half of patients were GTCS-free after fenfluramine. For context, the analysis included 360 patients with DS, 176 with DS, 10 with Sunflower syndrome, 6 with CDKL5 deficiency disorder, 3 with SCN8A-related disorder, and 6 with other developmental and epileptic encephalopathies.2

"These data demonstrated striking levels of GTCS control, setting new standards for what can be achieved in Dravet syndrome, but also providing important insights into treatment for other developmental and epileptic encephalopathies,” lead author Helen Cross, head of the Developmental Neuroscience Program, University College London, said in a statement. "These seizures are one of our main concerns because of the risk of SUDEP (Sudden Unexpected Death in Epilepsy)."

Another abstract assessed the safety and efficacy of adult patients with DS who did not participate in the phase 3 clinical trials but enrolled in the open-label extension (OLE) study de novo. Comprised of 28 patients, demographics, incidence of treatment-emergent adverse events (TEAEs), ratings on the Clinical Global Impression-Improvement (CGI-I) scale, and percent change in monthly convulsive seizure frequency (MCSF) per 28 days were summarized. Mean age at enrollment was 25.4 years (range, 19.3-33.3).3

READ MORE: Rapid Administration of Diazepam Results in Improved Seizure Cluster Cessation, Shorter Seizures

TEAEs were found in almost all patients (26 of 28), with decreased appetite (42.3%), fatigue (19.2%), upper respiratory tract infection (19.2%), nasopharyngitis (15.4%), and somnolence (15.4%) reported. At the last visit, investigators and caregivers rated 20/28 and 22/28, respectively, that patients were "improved" on CGI-I. In 17 patients who had both baseline and post-baseline seizure data, a median 50.2% MCSF reduction from baseline over the entire OLE (P <.001) was reported. Investigators reported no cases of valvular heart disease or pulmonary arterial hypertension.

"The impact of Dravet and Lennox-Gastaut syndromes are far reaching, with many emotional and practical consequences for parents, siblings, relatives and loved ones," Orrin Devinsky, MD, director of NYU Langone’s Comprehensive Epilepsy Center, said in a statement.1 "These data are raising the bar in what can be achieved in advancing the care for both children and adults living with these difficult to treat conditions."

A comparative analysis of clinical trial data further highlighted fenfluramine’s impact on drop seizure frequency (DSF) in dose-capped patients with LGS. In the randomized controlled trial, 76 adults (18-35 years) and 187 children/adolescents (2-17 years) were randomly assigned to fenfluramine 0.7 mg/kg/day (n = 25 and 62, respectively), fenfluramine 0.2 mg/kg/day (n = 25 and 64), or placebo (n = 26 and 61). Patients were dose-capped at 26 mg/day and assessed on effect and tolerability after 1 month.4

Among both adults and children/adolescents, findings showed that the median DSF reduction from baseline was numerically greater in the 0.7 mg/kg/day fenfluramine group (36.3% vs 17.8%; P = .0877; and 20.3% vs 4.8%; P = .0106). In a subgroup (n = 47) of those who weighted more than 37.5 kg and had medication capped at 26 mg/day, findings showed that the median percentage reduction from baseline in DSF was greater in fenfluramine-treated patients than placebo (n = 45; 35.3% vs 11.2%; P = .0079).

In the open-label extension of the trial, most patients (75%) received less than 0.5 mg/kg/day of fenfluramine. Using Wilcoxon rank test, the data revealed a 39.0% median percentage reduction in DSF in adults (n = 70; P <.0001) and 25.6% reduction in children/adolescents (n = 171; P = .0037). Fenfluramine continued to be effective in reducing DSF regardless of patients weighing less than or more 37.5 kg (<37.5 kg: 28.3%; P = .0127; >37.5 kg: 29.0%; P <.0001).

1. UCB presents new data at 35th International Epilepsy Congress (IEC) highlighting important advancements across Fintepla (fenfluramine) oral solution and broader epilepsies portfolio. News release. UCB Pharma. August 31, 2023. Accessed September 8, 2023.
2. Cross H, Devinsky O, Gil-Nagel A. Effect of Fenfluramine on Generalized Tonic-Clonic Seizures in Rare Epilepsy Syndromes: A Review of Published Studies. Poster presented at: International Epilepsy Congress (IEC); 2023, September 2-6; Dublin, Ireland.
3. Sanchez-Carpintero R, Devinsky O, Gil-Nagel A. Safety and Efficacy of Fenfluramine in Adult Patients with Dravet Syndrome Enrolled De Novo in an Open-Label Extension Study. Poster presented at: International Epilepsy Congress (IEC); 2023, September 2-6; Dublin, Ireland.
4. Scheffer IE, Ceulemans B, Sullivan J, et al. Impact of Fenfluramine on Drop Seizure Frequency in Adults or Dose-Capped Patients With Lennox-Gastaut Syndrome: Comparative Analysis of Clinical Trial Data. Poster presented at: International Epilepsy Congress (IEC); 2023, September 2-6; Dublin, Ireland.
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