Trial reportEpilepsia2023
Fenfluramine provides clinically meaningful reduction in frequency of drop seizures in patients with Lennox-Gastaut syndrome: Interim analysis of an open-label extension study.
Trial report in Epilepsia, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. It is linked to trial NCT03355209 (A Two-Part Study of ZX008 in Children and Adults With Lennox-Gastaut Syndrome), which is not on this map. Cited by 34 papers, 3 of them syntheses that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
A Two-Part Study of ZX008 in Children and Adults With Lennox-Gastaut Syndrome (LGS); Part 1: A Randomized, Double-blind, Placebo-controlled Trial of Two Fixed Doses of ZX008 (Fenfluramine Hydrochloride) Oral Solution as Adjunctive Therapy for Seizures in Children and Adults With LGS, Followed by Part 2: An Open-label Extension to Assess Long-Term Safety of ZX008 in Children and Adults With LGS
Who cites it
34 citing papers in PubMed, 3 syntheses or guidelines pooled it, 45 citations in OpenAlex.
- SUDEP and mortality in developmental and epileptic encephalopathies: A meta-analysis of randomized clinical trials and extension studies.Epilepsia · 2026Pooled it
- Efficacy and safety of pharmacological and non-pharmacological therapies in Lennox-Gastaut syndrome: a systematic review and network meta-analysis.Frontiers in pharmacology · 2025Pooled it
- [Advances and guidance in the treatment of drug-resistant epilepsy: a review by the Andalusian Epilepsy Society of the new drugs cenobamate, fenfluramine and cannabidiol].Revista de neurologia · 2024Guideline
- Trial
- Trial
- Sudden unexpected death in epilepsy: An Italian expert consensus statement on risk, mechanisms, prevention, and therapeutic strategies.Epilepsia open · 2026Article
- Fenfluramine for seizures in Dravet syndrome and Lennox-Gastaut syndrome: Mechanisms, clinical evidence, safety, and practical integration.Epilepsy & behavior reports · 2026Review
- Changes in effectiveness and safety in patients with Lennox-Gastaut syndrome transitioning from the fenfluramine randomized controlled trial to open-label extension study.Epilepsia open · 2026Article
- Practical Recommendations for Cardiology Follow-Up in Patients Treated with Fenfluramine Based on Expert Opinion and Clinical Experience.Neurology and therapy · 2026Review
- Reversible Pulmonary Arterial Hypertension Due to Fenfluramine in a Young Child: A Case Report.Cureus · 2026Article
- Epilepsy: Molecular Pathogenesis and Emerging Therapies.MedComm · 2026Review
- Safety of Drugs Used in Difficult-to-Treat Epileptic Syndromes: A Disproportionality Analysis Using the Eudravigilance Database.Pharmaceuticals (Basel, Switzerland) · 2025Article
- Fenfluramine for seizures associated with Dravet syndrome and Lennox-Gastaut syndrome.Australian prescriber · 2025Review
- Epileptic drop attacks: More than just atonic seizures.Epilepsia open · 2025Article
- Review
- Article
- Fenfluramine: an effective treatment for developmental epileptic encephalopathies beyond Dravet and Lennox-Gastaut Syndromes.Journal of neurology · 2025Article
- Electroclinical Landscape of Infantile Epileptic Spasms Syndrome.Indian journal of pediatrics · 2025Article
- Expert-Agreed Practical Recommendations on the Use of Fenfluramine in Developmental and Epileptic Encephalopathies Based on Clinical Experience and Literature Review.Neurology and therapy · 2025Review
- Treatment of Seizures in People with Intellectual Disability.CNS drugs · 2025Review
Corrections and comments
- Erratum issued
Authors and funding
19 authors at 14 institutions in 7 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
objectiveThis study was undertaken to evaluate the long-term safety and effectiveness of fenfluramine in patients with Lennox-Gastaut syndrome (LGS).
methodsEligible patients with LGS who completed a 14-week phase 3 randomized clinical trial enrolled in an open-label extension (OLE; NCT03355209). All patients were initially started on .2 mg/kg/day fenfluramine and after 1 month were titrated by effectiveness and tolerability, which were assessed at 3-month intervals. The protocol-specified treatment duration was 12 months, but COVID-19-related delays resulted in 142 patients completing their final visit after 12 months.
resultsAs of October 19, 2020, 247 patients were enrolled in the OLE. Mean age was 14.3 ± 7.6 years (79 [32%] adults) and median fenfluramine treatment duration was 364 days; 88.3% of patients received 2-4 concomitant antiseizure medications. Median percentage change in monthly drop seizure frequency was -28.6% over the entire OLE (n = 241) and -50.5% at Month 15 (n = 142, p < .0001); 75 of 241 patients (31.1%) experienced ≥50% reduction in drop seizure frequency. Median percentage change in nondrop seizure frequency was -45.9% (n = 192, p = .0038). Generalized tonic-clonic seizures (GTCS) and tonic seizures were most responsive to treatment, with median reductions over the entire OLE of 48.8% (p < .0001, n = 106) and 35.8% (p < .0001, n = 186), respectively. A total of 37.6% (95% confidence interval [CI] = 31.4%-44.1%, n = 237) of investigators and 35.2% of caregivers (95% CI = 29.1%-41.8%, n = 230) rated patients as Much Improved/Very Much Improved on the Clinical Global Impression of Improvement scale. The most frequent treatment-emergent adverse events were decreased appetite (16.2%) and fatigue (13.4%). No cases of valvular heart disease (VHD) or pulmonary arterial hypertension (PAH) were observed. SIGNIFICANCE: Patients with LGS experienced sustained reductions in drop seizure frequency on fenfluramine treatment, with a particularly robust reduction in frequency of GTCS, the key risk factor for sudden unexpected death in epilepsy. Fenfluramine was generally well tolerated; VHD or PAH was not observed long-term. Fenfluramine may provide an important long-term treatment option for LGS.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.