Fintepla (low-dose fenfluramine) / UCB, Nippon Shinyaku - LARVOL DELTA

Treatment of epilepsy using newer antiseizure medications: A retrospective cohort study of prescription patterns in Sweden 2013-2022. (PubMed, Epilepsia) - "Our observations indicate that prescription patterns of the newer ASMs comply with the currently approved indications for the respective medications for a majority of patients (prevalence of brivaracetam as adjunctive treatment is somewhat lower). Retention on the dispensed medications are in line with what would be expected for adjunctive treatment of patients with drug-resistant epilepsies."

Journal • Retrospective data • CNS Disorders • Epilepsy

Drug discovery and preclinical testing of drug candidates for developmental and epileptic encephalopathies. (PubMed, Epilepsia) - "In conclusion, testing strategies need to be carefully tailored to the candidate drug or therapeutic approach. In this context, there is an urgent need for development of further specific DEE models and for a comprehensive characterization of the face and predictive validity of existing and future DEE models."

Journal • Preclinical • Review • CNS Disorders • Developmental Disorders • Epilepsy

Efficacy of Low-Dose Fenfluramine on Adult Patients With Lennox-Gastaut Syndrome. (PubMed, Cureus) - "Conclusion Low-dose fenfluramine may effectively manage seizures in adult patients with LGS while reducing adverse effects. This case series provides a growing body of real-world data regarding the use of fenfluramine in this patient population."

Journal • Anorexia • CNS Disorders • Epilepsy

FDA may approve fenfluramine to treat epilepsy (Taipei Times) - "The Food and Drug Administration (FDA) announced that it is considering allowing the use of amphetamine-like drug fenfluramine to treat forms of epilepsy that are otherwise difficult to treat and resistant to traditional anti-epileptic drugs....The FDA, under the Ministry of Health and Welfare (MOHW), on Tuesday announced draft revisions to the regulations on amphetamine-like substances and their derivatives, with a 14-day window for public comment."

FDA event • Epilepsy

Enantioselective comparative analysis of the anticonvulsant potency of fenfluramine and norfenfluramine in mice. (PubMed, Epilepsia) - "These findings are relevant in determining which enantiomer is most suitable for clinical development as a stereoselectively pure follow-up compound to the marketed racemic fenfluramine, and indicate that l-fenfluramine has superior antiseizure activity over l-norfenfluramine in the MES model. This study also illustrates the limitations of relying solely on dose-response curves, and the added value of assessing concentration-response relationships."

Journal • Preclinical • Cardiovascular • CNS Disorders • Epilepsy

Efficacy and tolerability of fenfluramine with concomitant potassium bromide in patients with Dravet syndrome. (PubMed, Epilepsia Open) - "This study investigated the combination of fenfluramine (FFA) and potassium BR in treating Dravet syndrome. It was found that it is effective in reducing seizures, but BR levels often went up after starting FFA, which caused side effects like drowsiness in many patients. In some cases, these side effects were serious enough that physicians had to stop either BR or FFA. The study highlights the need for careful monitoring of BR levels when using this combination to avoid potential side effects by reducing the BR dose early if needed."

Journal • Anesthesia • Anorexia • CNS Disorders • Epilepsy

Drosophila melanogaster as a rapid in vivo assay system for preclinical anti-seizure medication testing. (PubMed, Epilepsia Open) - "Effective human anti-seizure medications (e.g., clobazam, stiripentol, and fenfluramine) reduced seizures, while sodium channel blockers like phenytoin worsened them. The Drosophila model offers a promising and efficient way to study genetic epilepsies and test treatments, accelerating the development of more targeted therapies."

Journal • Preclinical • CNS Disorders • Epilepsy

A Study to Assess Drug-drug Interaction of ZX008 in Healthy Male and Female Study Participants (clinicaltrials.gov) - P1 | N=22 | Completed | Sponsor: UCB BIOSCIENCES, Inc. | Active, not recruiting ➔ Completed

Trial completion

Real-World safety profile of Fenfluramine in refractory epilepsy: a pharmacovigilance study based on FAERS database. (PubMed, Epilepsy Behav) - "In conclusion, while Fenfluramine demonstrates clear therapeutic benefits for refractory epilepsy, these findings emphasize the necessity for comprehensive risk assessment in clinical practice."

Adverse events • Journal • Real-world evidence • Behavior Disorders • CNS Disorders • Epilepsy • Infectious Disease • Mental Retardation • Pneumonia • Psychiatry • Respiratory Diseases

Emerging Insights into the Pathogenic Mechanisms of Dravet Syndrome. (PubMed, Neurochem Res) - "Recently approved drugs such as cannabidiol (CBD) and fenfluramine (FFA) also help to better understand the mechanisms underlying the different disease symptoms...We also propose that in DS, one of the main consequences of the defective GABAergic signalling during development is to impair glial cells maturation and functions, including their role in synaptogenesis, synaptic refinement and inflammatory responses. Developing new tools to restore GABAergic signalling and/or glial functions may pave the way for new more effective treatments in Dravet Syndrome."

Journal • Review • ADHD (Impulsive Aggression) • Alzheimer's Disease • Attention Deficit Hyperactivity Disorder • CNS Disorders • Cognitive Disorders • Developmental Disorders • Epilepsy • Inflammation • Mood Disorders • Psychiatry • NAV1

A Study to Investigate the Long-Term Safety of ZX008 (Fenfluramine Hydrochloride) Oral Solution in Children and Adults With Epileptic Encephalopathy Including Dravet Syndrome and Lennox-Gastaut Syndrome (clinicaltrials.gov) - P3 | N=412 | Completed | Sponsor: Zogenix, Inc. | Active, not recruiting ➔ Completed

Trial completion • CNS Disorders • Epilepsy

Current and emerging pharmacotherapies in lennox-Gastaut syndrome. (PubMed, Expert Opin Pharmacother) - "This review examines FDA-approved medications for LGS (clonazepam, felbamate, lamotrigine, topiramate, rufinamide, clobazam, cannabidiol, and fenfluramine), commonly used off-label antiseizure medications, emerging treatments in clinical trials, and precision therapeutics targeting etiology-specific mechanisms. Future progress depends on improved natural history studies, standardized data collection, advanced preclinical models, innovative trial designs, and addressing healthcare inequities. While emerging precision therapies targeting genetic causes show promise, the field urgently needs better strategies to optimize existing treatments while developing disease-modifying approaches that address both seizures and non-seizure outcomes."

Journal • Review • Alzheimer's Disease • CNS Disorders • Cognitive Disorders • Epilepsy • Gene Therapies

Drug-drug interaction between anti-seizure medications in dravet syndrome and lennox-gastaut syndrome. (PubMed, Expert Opin Drug Metab Toxicol) - "Digital tools and decision-support apps can assist clinicians in quickly assessing DDIs and selecting the most effective drug combinations. Ongoing research in pharmacogenetics and personalized medicine holds promise for improving the management of complex conditions like DS and LGS, offering potential for better, individualized therapeutic strategies."

Journal • Review • CNS Disorders • Epilepsy

Rapidly Fatal Pulmonary Arterial Hypertension: Phentermine Precipitating Right Ventricular Failure in a Woman With Lupus (ATS 2025) - "This abstract is funded by: None Introduction: Phentermine is an anorexigen previously approved for short term use along with fenfluramine as a treatment for obesity...She was discharged on furosemide and sildenafil with outpatient follow up...She was transferred to the ICU and started on milrinone and vasopressin for right ventricular failure...A review of recent literature showed only 1 case of PAH in a previously healthy 29-year-old associated with recent phentermine use. We believe phentermine, in this undiagnosed lupus patient with likely very mild underlying PAH, lead to decompensation of her right ventricle leading to rapid mortality."

Clinical • Acute Kidney Injury • Cardiovascular • Genetic Disorders • Immunology • Inflammatory Arthritis • Lupus • Metabolic Disorders • Nephrology • Obesity • Pulmonary Arterial Hypertension • Renal Disease • Respiratory Diseases

Seizure-type-specific treatment responses in Lennox-Gastaut Syndrome: A comprehensive review of pharmacological, neuromodulatory, dietary, and surgical therapies. (PubMed, Epilepsy Behav) - "Generalized tonic-clonic seizures (GTCS) show favorable responses to antiseizure medications (ASMs) such as felbamate, lamotrigine, topiramate, fenfluramine, lacosamide, and perampanel. Myoclonic seizures tend to respond better to clonazepam, topiramate, zonisamide, brivaracetam, and perampanel, but may show limited responsiveness to neuromodulation and CC. Atypical absence seizures may respond to valproate, topiramate, and rufinamide, but show poor responses to brivaracetam and perampanel...This review underscores the importance of tailoring treatment to predominant seizure types and calls for more rigorous, seizure-type-specific outcome reporting in future clinical trials, along with the need for long-term studies. The findings advocate for a precision, network-based approach to treatment, where therapeutic decisions are guided by individual seizure patterns and supported by evidence-based, seizure-type-specific efficacy data."

Journal • Review • Absence Seizure Disorder • CNS Disorders • Epilepsy

A Study to Investigate the Efficacy and Safety of ZX008 in Subjects With CDKL5 Deficiency Disorder (clinicaltrials.gov) - P3 | N=87 | Active, not recruiting | Sponsor: Zogenix, Inc. | Trial completion date: Jun 2026 ➔ Nov 2027 | Trial primary completion date: Feb 2025 ➔ Nov 2027

Trial completion date • Trial primary completion date • CNS Disorders • Epilepsy • Genetic Disorders • CDKL5

Successful use of fenfluramine in drug resistant epileptic encephalopathy with spike-wave activation in sleep (EE-SWAS)- an automated EEG study. (PubMed, Seizure) - No abstract available

Journal • CNS Disorders • Epilepsy

Fenfluramine: an effective treatment for developmental epileptic encephalopathies beyond Dravet and Lennox-Gastaut Syndromes. (PubMed, J Neurol) - "FFA demonstrates effectiveness and tolerability in patients with DEEs in a real-world setting, and has potential as a broad-spectrum ASM, effective across a wide range of DEEs, seizure types, and patient profiles."

Journal • Retrospective data • Anorexia • CNS Disorders • Epilepsy • Immunology

Seizures influence sleep macrostructure and the sleep-wake circadian rhythm in Dravet syndrome. (PubMed, Epilepsia) - "Our study shows a significant effect of epileptic phenomena on sleep macrostructure in DS. Motor seizures and IEDs influence slow wave sleep, which could be one of the mechanisms that sustain encephalopathy in DS. Interestingly, fenfluramine seems to have a protective effect on this mechanism, both by stabilizing sleep and as an ASM."

Journal • CNS Disorders • Epilepsy • Sleep Disorder

Appropriate selection of participants in pediatric developmental and epileptic encephalopathy trials: Lessons learned and future opportunities. (PubMed, Epilepsia) - "Furthermore, 23% of DS participants and 32% of LGS participants had at least one seizure reclassified; 63.8% of DS sites and 78% of LGS sites had at least one participant with a seizure reclassification. Independent, central review of participants in pediatric ASM trials improves consistency across study sites, as well as overall accuracy of syndromic diagnosis and seizure classification, and may reduce placebo response rate."

Journal • CNS Disorders • Epilepsy • Pediatrics

The serotonin precursor 5-HTP and the serotonin releaser fenfluramine but not the serotonin reuptake inhibitor escitalopram impair acquisition and expression of context-conditioned fear. (PubMed, Behav Brain Res) - "In contrast, neither 5-HTP nor fenfluramine impacted expression of conditioned fear when administered immediately after the exposure to shocks. The results underline the importance of an intact and physiologically regulated serotonergic transmission for fear conditioning in rats."

Journal • Mood Disorders • Psychiatry

A Postmarketing Pharmacovigilance Study of Fenfluramine: Adverse Event Data Mining and Analysis Based on the US Food and Drug Administration Public Data Open Project (openFDA). (PubMed, Pediatr Neurol) - "This study employed the openFDA database to identify safety signals associated with FFA, thereby offering significant insights for clinical monitoring and risk identification in patients undergoing FFA therapy."

Adverse events • Journal • P4 data • CNS Disorders • Epilepsy

UCB presents latest research across leading neurology portfolio at American Academy of Neurology (AAN) meeting 2025 (PRNewswire) - "24 scientific abstracts reflect UCB's ongoing commitment to improving outcomes for people living with neurological conditions, including rare epilepsies Dravet syndrome and Lennox-Gastaut syndrome, as well as generalized myasthenia gravis and thymidine kinase 2 deficiency; Research includes disease course data of untreated patients with thymidine kinase 2 deficiency from largest international dataset; Also features new data on generalized myasthenia gravis treatments RYSTIGGO (rozanolixizumab-noli) and ZILBRYSQ (zilucoplan) including an open-label extension study investigating rozanolixizumab self-administration and a phase 3 study on the effect of zilucoplan on specific outcome scores; Data on FINTEPLA (fenfluramine), BRIVIACT (brivaracetam) CV, and investigational therapy STACCATO alprazolam showcase commitment to people living with epilepsies and their unmet needs."

Clinical data • Epilepsy • Immunology • Myasthenia Gravis

EXACERBATION OF MITRAL VALVE REGURGITATION IN A B-ALL PATIENT UNDERGOING IMMUNOTHERAPY - Ushma Majmudar (ACC 2025) - "Background: T cell therapy (TCT) rarely causes isolated severe valvular pathology without cardiomyopathy, but its hemodynamic effects can considerably exacerbate mitral regurgitation (MR) in patients with subtle valvular issues.Case: A 48-year-old woman with a history of fenfluramine (FF) use for weight loss 10 years prior developed a cryptogenic stroke and 5 months later, was diagnosed with B-ALL...After her second blinatumomab (BL) cycle, she developed dyspnea... We emphasize the importance of considering prior FF use when evaluating patients with idiopathic MR. We also demonstrate how hemodynamic changes from TCT can worsen MR and show how careful hemodynamic management can enable the safe resumption of these lifesaving therapies."

Clinical • Cardiomyopathy • Cardiovascular • Metabolic Disorders • Pulmonary Disease • IL6

Efficacy and safety of pharmacological and non-pharmacological therapies in Lennox-Gastaut syndrome: a systematic review and network meta-analysis. (PubMed, Front Pharmacol) - "The treatments assessed included cannabidiol, fenfluramine, clobazam, rufinamide, felbamate, lamotrigine, topiramate, deep brain stimulation, and anterior corpus callosotomy. Clobazam 1 mg/kg/day, anterior corpus callosotomy, and rufinamide manifested the most optimal efficacy in seizure control among LGS patients. Caution should be exercised when administering cannabidiol, lamotrigine, and fenfluramine 0.7 mg/kg/day in clinical practice to mitigate safety concerns associated with drug-related side effects."

Journal • Retrospective data • Review • CNS Disorders • Epilepsy