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

Fenfluramine for late-onset epileptic spasms. (PubMed, Epileptic Disord) - No abstract available

Journal • CNS Disorders • Epilepsy

Relieving the Weight: Fenfluramine's Re-emergence as Antiseizure Medication for Lennox-Gastaut and Dravet Syndrome. (PubMed, Ann Pharmacother) - "As seen through the results of multiple clinical trials, fenfluramine can provide significant seizure reduction for Lennox-Gastaut and Dravet patients with treatment-resistant seizures. Risks can be mitigated through adherence to proper programs and schedules, and can provide enough benefits to outweigh risks in patients with particularly resistant epilepsies."

Journal • Review • Cardiovascular • CNS Disorders • Epilepsy • Pediatrics

Reply to Chen et al. "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) - No abstract available

Adverse events • Journal • P4 data

Association of Fenfluramine Treatment and Everyday Executive Functioning in Adult Patients With Lennox-Gastaut Syndrome (AES 2025) - P3 | "In this post hoc analysis, clinically meaningful improvements in EEF were seen in adults with LGS treated with FFA in the RCT; consistent improvements were seen in the 12-mo OLE. There were no strong correlations between reductions in seizures associated with a fall and improvements in EEF, suggesting that these outcomes were partly independent of each other."

Clinical • Late-breaking abstract • CNS Disorders • Developmental Disorders • Epilepsy • Mental Retardation

Healthcare Resource Utilization and Antiseizure Medication Claims in Patients With Lennox-Gastaut Syndrome Receiving Fenfluramine in the United States (AES 2025) - "FFA use in patients with LGS was associated with reductions in ER visits (all-cause and seizure-related), inpatient hospitalizations (all-cause and seizure-related), and ambulance use. The results for ER visits and ambulance use remain robust, following more rigorous analytical approaches. The average number of all ASM claims and unique ASM claims per patient decreased following FFA initiation, suggesting that treatment with FFA reduces the total ASM drug load in patients with LGS."

Clinical • HEOR • Late-breaking abstract • CNS Disorders • Epilepsy

Outcomes of pediatric and adult patients with fenfluramine in a real-life setting (AES 2025) - "Outcomes in a real-life children and adult patient population treated with FFL showed promising efficacy with a good tolerability profile. Further information is needed to consolidate results in clinical practice"

Clinical • CNS Disorders • Epilepsy • Pediatrics

FENFLU-Norte: Multicenter Experience with Fenfluramine in Northern Spain FENFLU-Norte: Multicenter Experience with Fenfluramine in Northern Spain (AES 2025) - "Real-world experience supports the use of FFA as an effective and well-tolerated therapeutic option."

Clinical • CNS Disorders • Epilepsy

Fenfluramine in CDKL5 Deficiency Disorder: Primary Efficacy and Safety Results From a Phase 3, Randomized, Double-Blind, Placebo-Controlled Study (AES 2025) - P3 | "In this first RCT evaluating FFA in pts with CDD, FFA provided significantly greater reduction in CMSF compared with PBO and was generally well tolerated; TEAEs were consistent with the known safety profile of FFA in Dravet and Lennox-Gastaut syndromes. These data suggest that FFA may be a promising therapy for treating seizures in pts with CDD."

Clinical • Late-breaking abstract • P3 data • Cardiovascular • CNS Disorders • Epilepsy • Genetic Disorders • Heart Failure • Pulmonary Arterial Hypertension • Respiratory Diseases • CDKL5

Preclinical Findings of Relutrigine, a Functional State Sodium Channel Modulator, Point to Anticonvulsant Potential in Dravet Syndrome with Greater Potency than Fenfluramine (AES 2025) - "Preliminary findings in a zebrafish model support relutrigine's anticonvulsant action in Dravet syndrome and the potential for superior efficacy over current standard-of-care. In combination with recent results from the EMBOLD study in SCN2A and SCN8A, these findings emphasize its promising potential to address significant unmet needs across broad DEEs."

Preclinical • CNS Disorders • Developmental Disorders • Epilepsy • SCN8A

Evaluation of ASM with new mechanisms of action in the GAERS model of absence seizure (AES 2025) - "Indeed, SWD in GAERS are inhibited by the anti-seizure medications (ASM) used to treat absence seizures, such as ethosuximide, valproate and lamotrigine. But SWD in GAERS are also aggravated by ASM or other drugs known for worsening absence in patients, e.g. carbamazepine or vigabatrin.Some recent compounds with antiseizure properties and specific mechanisms of action have never been evaluated in the GAERS...Retigabine (4-8 mg/kg PO) produced a significant aggravation of SWD... Evaluation of new mechanisms of action in the GAERS may provide fresh hypothesis for the development of new compounds addressing absence seizures. Our study indicates that targeting potassium channels may be at risk of aggravating SWD, whereas targeting the 5-HT system may produce an interesting effect on absence seizures."

Absence Seizure Disorder • Anesthesia • CNS Disorders • Epilepsy

Real-World Utilization of Stiripentol in Children Aged 3 Years and Younger: A US Perspective (AES 2025) - "At STP initiation, 77% of patients/caregivers reported use of clobazam. Thirty percent of patients had been on cannabidiol (21%) or fenfluramine (9%) prior to starting STP (Table 2)... This analysis represents the 1st, US-led real-world perspective of STP use in patients <3 since the label expansion in 2022. This cohort was dosed near the recommended STP maintenance dose (50mg/kg/day) which aligns with the original RCT. Less than 10% of patients reported somnolence or decreased weight/appetite as an adverse event suggesting increased tolerability."

Clinical • Real-world • Real-world evidence • CNS Disorders • Epilepsy

Practical Consensus Recommendations for Polytherapy Involving Stiripentol in Dravet Syndrome: A Nominal Group Approach (AES 2025) - "The therapeutic arsenal includes non-specific first-line treatments (valproate and clobazam), specific therapies including stiripentol (STP), cannabidiol (CBD) fenfluramine (FFA), and other ASMs such as bromide, topiramate and levetiracetam. This expert consensus, developed through a nominal group technique and supported by an independent vote from international clinicians, provides a framework for all physicians managing DS to evaluate and refine their polytherapy practices with the goal of improving patient care."

CNS Disorders • Epilepsy

Final Results From a Long-Term Open-Label Extension Study (Up to 4 Years): Tolerability of Fenfluramine and Global Functioning of Pediatric and Adult Patients With Dravet or Lennox-Gastaut Syndromes (AES 2025) - P1, P3 | "Last FFA doses from the prior studies were continued, then flexibly titrated as needed (max FFA 0.7 mg/kg/d [26 mg/d] without stiripentol [STP] or FFA 0.4 mg/kg/d [17 mg/d] with STP). In this OLE study of patients with DS or LGS, TEAEs were consistent with the known FFA safety profile, and no new or unexpected safety signals were observed. Investigator and caregiver CGI–I ratings suggested sustained clinical benefit (median overall FFA exposure = 4 years). These data support long-term FFA use in pediatric and adult patients with DS or LGS."

Clinical • Late-breaking abstract • Cardiovascular • CNS Disorders • Developmental Disorders • Epilepsy • Heart Failure • Pediatrics • Pulmonary Arterial Hypertension • Respiratory Diseases

Need for Reintroduction of Stiripentol After Weaning in Patients with Dravet Syndrome: A Multicenter Case Series (AES 2025) - "We aimed to evaluate polypharmacy management in DS individuals treated with stiripentol (STP), an approved adjunctive therapy to clobazam (CLB) in the US, and to CLB and valproate (VPA) in Europe. Ten patients with DS from six centres who underwent STP weaning followed by reinstitution of STP were retrospectively ascertained, and descriptive analysis performed. STP was introduced in all patients for seizure control despite multiple prior ASM attempts (median 3 [range 1-7, n=9], most commonly VPA [88.9% patients], topiramate [55.6%], CLB [44.4%])...STP was tapered or discontinued after a median treatment duration of 102 months (range 17-203) for (i) AEs with add-on fenfluramine (FFA) (unsteadiness, tiredness and weight loss, myoclonic seizure cluster and moderate anorexia, severe psychiatric disorder, n=3), (ii) FFA clinical trials or dose increase (n=4), (iii) attempts to simplify polytherapy after seizure reduction with add-on FFA (n=2), cannabidiol (n=2) or ketogenic..."

Clinical • Late-breaking abstract • Absence Seizure Disorder • Anorexia • CNS Disorders • Constipation • Epilepsy • Gastroenterology • Gastrointestinal Disorder • Mental Retardation • Movement Disorders • Psychiatry

Efficacy and Tolerability of Fenfluramine with Concomitant Potassium Bromide in Patients with Dravet Syndrome (AES 2025) - "BR levels increased significantly after FFA initiation when BR doses were not reduced, contributing to adverse events—primarily somnolence—and resulting in the discontinuation of BR or FFA in some patients. Close monitoring of BR levels is crucial to minimizing the risk of adverse events."

Clinical • Late-breaking abstract • Anesthesia • Anorexia • CNS Disorders • Epilepsy

Spectrum of Lennox-Gastaut Syndrome in Adulthood: Clinical Features of 18 patients (AES 2025) - "Fenfluramine (FFA), formerly used as an appetite suppressant, has recently been approved for the treatment of LGS and has shown promising efficacy. A significant proportion of adult LGS patients did not fulfill the updated ILAE criteria. While these criteria refine the diagnosis of LGS, their strict application may limit access to syndrome-specific medications such as FFA and rufinamide (RUF). Nonetheless, seizure reduction was observed in patients treated with FFA based on classical diagnostic criteria, as demonstrated in our cohort."

Clinical • CNS Disorders • Developmental Disorders • Epilepsy • Mental Retardation

Practical Consensus Recommendations for Rational Polytherapy Involving Stiripentol in Dravet Syndrome: Preliminary results of a US Cohort (AES 2025) - "Consensus recommendations1 highlight valproic acid as 1st line treatment, stiripentol (STP), fenfluramine (FFA), and/ or clobazam (CLB) as 1st or 2nd line and other ASMs including cannabidiol (CBD), levetiracetam (LEV) and topiramate (TPM) as 3rd and 4th line. The preliminary results of the expert consensus on DS treatment, developed through a nominal group and validated by independent voting among US clinicians, provide a practical framework for US providers managing DS to help guide polytherapy decisions. The initial results reinforce the infrequent use of DS-specific ASMs highlighted in previous reviews.2 While there was a strong consensus supporting STP's efficacy when added to an existing ASMs, the data revealed limited provider confidence in the management of these DS-specific ASMs, including STP, underscoring the need for targeted education."

Late-breaking abstract • CNS Disorders • Epilepsy

Fenfuramine for adults with Lennox-Gastaut Syndrome - What is the impact? (AES 2025) - "Greatest efficacy was seen in those prescribed both Cenobamate and Fenfluramine. Fenfluramine appears to be efficacious in reducing convulsive seizures for those adults with highly refractory epilepsy in the context of LGS. Addition of Fenfluramine contributed to a substantial reduction in hospitalisations, with associated health-economic benefits. Assessment of efficacy needs to be individualised to reflect the variability in seizure pattern and frequency in this highly refractory population."

Clinical • CNS Disorders • Epilepsy

Utilization and Prescribing Patterns of Stiripentol for Dravet Syndrome: Preliminary Results of an International Physician Survey (AES 2025) - "Rationale: Stiripentol (STP) is approved for the treatment of seizures associated with Dravet Syndrome (DS) in patients taking clobazam who are 6 months of age and older...64.3% co-prescribed sodium valproate. Half prescribed STP in conjunction with fenfluramine (FFA), 75.0% with cannabidiol (CBD) with most (85.7%) adjusting the FFA dose when used in combination.When initiating therapy, providers prioritized seizure frequency (53.6%), seizure length (35.7%), and seizure character (10.7%)... Preliminary findings from this survey highlight a modest uptick in STP utilization in DS across experienced pediatric epilepsy specialists. While most providers reported experiencing clinical benefit, adverse effects, and insurance-related barriers were common. These findings suggest STP is utilized but variably implemented in practice, with opportunities to refine dosing strategies and address systemic barriers to optimize outcomes for patients with DS."

Late-breaking abstract • Anesthesia • CNS Disorders • Epilepsy

Real World Utilization of Stiripentol (STP) by United States (US) Prescribers: A 3-Year Analysis Update (AES 2025) - "Despite rational polytherapy recommendations and availability of DS-approved antiseizure medications (ASMs), stiripentol (STP), cannabidiol (CBD), and fenfluramine (FFA), integration into treatment regimens remains limited1...At STP initiation, 71% were taking clobazam (CLB), 33% CBD, and 21% on FFA (previously 75%, 37%, 24%)...Levetiracetam (16%) and valproic acid (15%) were the most common non-DS approved ASMs... This 3-year analysis shows STP dosing remained consistent and below the FDA-approved dose of 50 mg/kg/day, with higher doses in younger patients. Doses of STP increased with longer treatment duration, reflecting titration to maintenance dosing, which is critical for tolerability and reduced premature discontinuations. While maintenance doses in younger patients were consistent with approved dosing, patients ≥ 6 years received lower average STP doses even after 8+ months on therapy."

Clinical • Late-breaking abstract • Real-world • Real-world evidence • CNS Disorders • Epilepsy

Underutilization of FDA approved Dravet Syndrome Specific Therapies: Findings from a US Multi-Center Survey and Advisory Board (AES 2025) - "Despite the availability and international consensus recommendations for DS-approved antiseizure medications (ASMs), stiripentol (STP), fenfluramine (FFA), and cannabidiol (CBD), a recent analysis found that these ASMs have been underutilized in DS patients, with only 7% of patients prescribed STP, 16% FFA, and 28% CBD.1,2 A US multi-center survey and advisory board aimed to explore ASM selection, barriers to DS-specific ASM use, and strategies to improve alignment with international consensus recommendations.2 A voluntary survey was completed by 38 clinicians from 27, Level IV National Association of Epilepsy Centers (NAECs)... The survey identified valproate (47%) or clobazam (CLB) (24%) as the most common 1st line ASMs considered when a patient is diagnosed with DS, with levetiracetam as a common ASM already included in a patient's regimen... This analysis confirms underutilization of DS-approved ASM therapies in DS management, highlighting a gap between..."

Clinical • Late-breaking abstract • CNS Disorders • Epilepsy

Neurobeachin (NBEA) Gene Defect Associated Epileptic Encephalopathy: Responsiveness to Cenobamate (AES 2025) - "Cenobamate was titrated every two weeks at age 13 years, and patient became seizure free at a dose of 100mg daily, and was tapered off clobazami after several months being seizure free, he remains delayed in academics but less autistic like and fewer behavioral issues on daily fenfluramine(24mg) , valproate (1350mg), and cenobamate (100mg) at 50.8 kg.Patient 2 : 32 year old female diagnosed NBEA with epilepsy and autism at age 2 years with comorbid mood disorder, refractory epilepsy...She was started on cenobamate and tapered off oxtellar and continued valproate and lorazepam... NBEA is a rare DEE with refractory epilpesy and identification can lead to better treatment outcomes. Cenobamate therapy in two cases improved both seizure control and behavioral outcome. More research is warranted."

Autism Spectrum Disorder • CNS Disorders • Developmental Disorders • Epilepsy • Genetic Disorders • Mental Retardation • Mood Disorders • Ophthalmology • Psychiatry • NBEA

Efficacy of low-dose Fenfluramine on adult patients with Lennox-Gastaut syndrome (AES 2025) - "FFA at low doses may effectively manage seizures in adult patients with LGS while minimizing adverse effects. Larger prospective studies are warranted to validate these findings and establish long-term efficacy and safety in adult patients with LGS."

Clinical • Alzheimer's Disease • Anorexia • CNS Disorders • Cognitive Disorders • Epilepsy

Fenfluramine in Refractory Status Epilepticus and Acute Repetitive Seizures: Promising Clinical Results (AES 2025) - "Both were on midazolam infusions; one also received phenobarbital infusion. In this small retrospective series, fenfluramine was associated with clinical improvement in seizure control in some patients with SRSE and acute repetitive seizures. It facilitated the reduction or discontinuation of anesthetic agents. Given its manageable safety profile and observed benefits, FFA may be considered as a therapeutic option in treatment-resistant SE."

Clinical • Anesthesia • CNS Disorders • Epilepsy • Metabolic Disorders • CARS1 • CARS2 • TSC2

Fenfluramine Persistence in Patients With Lennox-Gastaut Syndrome: a Retrospective Analysis Using US Claims Data (AES 2025) - "In this first real-world evaluation of patients with LGS who received FFA, persistence was 73% and 61% at 6 and 12 months, respectively. No significant differences in demographic or clinical characteristics of FFA-persistent and nonpersistent patients were observed. Here, patients who received FFA were younger, resided in more socioeconomically disadvantaged neighborhoods, and had greater disease severity, including a greater number of previously attempted ASMs, compared with patients who did not receive FFA."

Late-breaking abstract • Retrospective data • Behavior Disorders • Cardiovascular • CNS Disorders • Epilepsy • Gastroenterology • Gastrointestinal Disorder • Mental Retardation • Psychiatry • Respiratory Diseases • Sleep Disorder