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

Fenfluramine (Fintepla) associated pulmonary hypertension: a study of adverse events reporting system FAERS (ERS 2026) - "For the 3 patients with documented follow-up, echocardiography showed a return to normal pressures, suggesting a potential toxicity reversibility. These results confirm the plausibility of PH onset in patients exposed to Fintepla, and reinforce the importance of careful monitoring."

Adverse events • Cardiovascular • CNS Disorders • Epilepsy • Heart Failure • Pulmonary Arterial Hypertension • Pulmonary Disease • Respiratory Diseases

ORCHID: A Study to Evaluate Safety, Tolerability, and Pharmacokinetics of Fenfluramine (Hydrochloride) in Infants 1 Year to Less Than 2 Years of Age With Dravet Syndrome (clinicaltrials.gov) - P3 | N=25 | Completed | Sponsor: UCB BIOSCIENCES, Inc. | Active, not recruiting ➔ Completed

Trial completion • CNS Disorders • Epilepsy

UCB's Fintepla reimbursement opens new option for hard-to-control Dravet syndrome (Korea Biomedical Review) - "The reimbursement, effective Sept. 1, follows Fintepla’s approval by the Ministry of Food and Drug Safety (MFDS) on Dec. 18, 2025, as an adjunctive treatment for seizures associated with Dravet syndrome in patients aged 2 years and older....Under the reimbursement criteria, Fintepla is covered for patients aged 2 years or older who have failed to achieve at least a 50 percent reduction in seizure frequency despite treatment with three or more existing anti-seizure medicines at sufficiently tolerated doses."

Reimbursement • CNS Disorders • Epilepsy

Efficacy of stiripentol, fenfluramine, and their combination on clinical outcomes in Dravet syndrome: A preliminary report. (PubMed, Epilepsia Open) - "Patients receiving fenfluramine-based regimens had a lower seizure burden than those receiving other antiseizure medications. Earlier initiation of stiripentol or fenfluramine was associated with better cognitive and motor outcomes, but these associations were substantially influenced by age, disease duration, and treatment era. Larger prospective studies are needed to determine whether earlier treatment independently influences long-term developmental outcomes."

Clinical data • Journal • CNS Disorders • Epilepsy • Mental Retardation • Movement Disorders • Psychiatry

Cognitive Side Effects of Antiseizure Medications in Adults with Epilepsy: An Update with a Focus on New Therapeutic Agents. (PubMed, CNS Drugs) - "Overall, newer-generation ASMs, including rufinamide, lacosamide, brivaracetam, cannabidiol, fenfluramine, and ganaxolone, demonstrate generally favourable cognitive profiles when used at recommended doses, particularly in monotherapy or rational polytherapy. Eslicarbazepine and cenobamate may be associated with mild, dose-dependent cognitive effects, occurring only at the upper end of the recommended dose range. In contrast, old ASMs and certain second-generation agents, notably topiramate and zonisamide, remain consistently associated with higher cognitive risks...Cognitive dysfunction in epilepsy is multifactorial, reflecting the interaction between disease-related neurobiological mechanisms and treatment effects. Optimal management requires balancing seizure control with cognitive preservation through individualised drug selection, cautious titration, and minimisation of polytherapy to achieve the best functional and quality-of-life outcomes."

Adverse events • Journal • Review • CNS Disorders • Cognitive Disorders • Developmental Disorders • Epilepsy • Mental Retardation

Implementation and use of risk minimization control tools in the EU: A multistakeholder survey. (PubMed, Br J Clin Pharmacol) - "RMCT implementation was generally perceived as feasible, although regulatory implementation was more challenging than integration into healthcare. Successful implementation may benefit from flexible design, alignment with existing systems, feasibility assessment, stakeholder engagement and clear guidance."

Journal

Impact of novel anti-seizure medications on status epilepticus in Dravet syndrome: a multicenter real-world cohort study. (PubMed, Seizure) - "In this large real-world cohort, early benzodiazepine administration was highly effective for SE management. Exposure to novel ASMs was associated with a reduced SE burden, supporting optimized long-term therapy to reduce SE frequency and severity in DS."

Journal • Real-world evidence • CNS Disorders • Critical care • Epilepsy • Pediatrics

Efficacy and safety of fenfluramine in Dravet syndrome: The impact of patient clinical characteristics. (PubMed, Epilepsia Open) - "Patients with Dravet syndrome struggle with seizures and everyday life. In three studies, patients aged 2-18 years received fenfluramine or placebo (sugar pill). Fenfluramine lowered seizures without many side effects. Researchers combined results from these studies to see how fenfluramine worked in different patient groups based on age, number of previous medications, and a gene called SCN1A. They looked at seizure reduction and whether doctors felt patients had improved. In all groups, fenfluramine worked better than placebo, with similar side effects. Researchers believe fenfluramine helped these patients, but some groups were small, so these results need to be confirmed."

Journal • CNS Disorders • Epilepsy • Pediatrics • CSF1

Pharmacokinetics, Safety, and Dosing of Antiseizure Medications in Patients with Renal or Hepatic Impairment. (PubMed, Clin Pharmacokinet) - "Ten newer antiseizure medications (ASMs) approved since 2000 and selected for this review (cenobamate, brivaracetam, eslicarbazepine acetate, lacosamide, perampanel, fenfluramine, ganaxolone, cannabidiol, stiripentol, and rufinamide) have broadened treatment options for drug-resistant epilepsy. Regulatory discrepancies between FDA and EMA labeling were identified for all ten agents, notably divergent hepatic dose caps for perampanel and cenobamate, conflicting renal recommendations for fenfluramine, and discordant guidance for eslicarbazepine acetate in severe renal impairment. These agents exhibit no uniform class effect in organ impairment; prescribing must be governed by agent-specific disposition profiles, organ-function severity, and free-drug monitoring for highly protein-bound agents like perampanel and ganaxolone."

Journal • PK/PD data • Review • CNS Disorders • Epilepsy • Hepatology • Nephrology • Renal Disease

A Phase 3 Study of Fenfluramine Hydrochloride in Rett Syndrome (clinicaltrials.gov) - P3 | N=200 | Recruiting | Sponsor: UCB BIOSCIENCES, Inc. | Not yet recruiting ➔ Recruiting | Trial completion date: Nov 2030 ➔ Aug 2031 | Trial primary completion date: Aug 2028 ➔ Feb 2029

Enrollment open • Trial completion date • Trial primary completion date • Developmental Disorders • Movement Disorders

Pathway- and region-specific serotonergic modulation in the dentate gyrus. (PubMed, Neuroscience) - "ELISA measurements showed that fenfluramine evoked greater 5-HT release from ventral hippocampal slices than from dorsal ones. These findings highlight pathway- and region-specific serotonergic modulation of inputs from the entorhinal cortex to the dentate gyrus and suggest a potential mechanism underlying the functional specialization of the hippocampus along its dorso-ventral axis."

Journal

Exploring the caregiver journey through randomized controlled trials in dravet syndrome: insights from a cross-sectional survey. (PubMed, Epilepsy Behav) - "To our knowledge, this is the first survey exploring the caregivers' perceptions of participation in epilepsy clinical trials. Patient and stakeholder engagement is essential for optimizing trial recruitment, acceptance and understanding of the failures."

Journal • CNS Disorders • Epilepsy • Pediatrics

Complex epilepsy phenotype associated with chromosome 2q24.2-q24.3 deletion involving sodium channel gene cluster. (PubMed, Ann Child Neurol Soc) - "The combination of ketogenic diet and fenfluramine is known to provide substantial benefits to patients with DS, but there is a paucity of literature regarding its role in other developmental and epileptic encephalopathies (DEE). His seizures are now responsive to rescue midazolam, and he no longer has status epilepticus. Our patient's remarkable clinical improvement suggests that this dual therapy may be beneficial in patients with DEE exhibiting pathogenic variations in this region of chromosome 2, beyond just DS."

Journal • CNS Disorders • Developmental Disorders • Epilepsy • Gastrointestinal Disorder

Fenfluramine: An Uncommon Cause of False Positive Urine Drug Testing: A Case Report. (PubMed, Ann Child Neurol Soc) - "Fenfluramine can result in a false-positive amphetamine urine drug screen at the recommended dose for Dravet syndrome. Awareness of this potential cross-reactivity can prevent undue child protective services reports, especially in patients at high risk for sudden death."

Journal • CNS Disorders • Epilepsy

Fenfluramine's Broader Potential: A Second Notable Electroencephalogram Response in Developmental Epileptic Encephalopathy With Spike-Wave Activation in Sleep. (PubMed, Ann Child Neurol Soc) - No abstract available

Journal • CNS Disorders • Epilepsy

A dramatic EEG response to fenfluramine in a patient with developmental and epileptic encephalopathy. (PubMed, Ann Child Neurol Soc) - No abstract available

Journal • CNS Disorders • Epilepsy

Beyond seizures in Dravet and Lennox-Gastaut syndromes - An Italian Expert Consensus on Non-Seizure issues and the role of fenfluramine. (PubMed, Epilepsy Behav) - "Incorporating NSI priorities into shared goal-setting and longitudinal monitoring may improve the clinical relevance of care in DS and LGS. The panel supported an NSI-informed, net-benefit approach to treatment optimization and identified FFA as a relevant option, while recognizing that evidence on NSI outcomes remains heterogeneous and should be strengthened through syndrome-specific, longitudinal assessment."

Journal • CNS Disorders • Epilepsy • Pediatrics

Changes in effectiveness and safety in patients with Lennox-Gastaut syndrome transitioning from the fenfluramine randomized controlled trial to open-label extension study. (PubMed, Epilepsia Open) - P3 | "Overall, the number of seizures (associated with a fall) decreased once patients initially receiving placebo changed to fenfluramine (optimal effect around Month 4 while receiving a higher dose), but as expected, common side effects were reported more frequently once patients began fenfluramine treatment. Patients, parents, and doctors should be aware of this time course to allow fenfluramine enough time to work."

Journal • CNS Disorders • Epilepsy

Antiseizure potency and neurotoxicity of the enantiomers of fenfluramine and norfenfluramine in rats and correlations with their concentrations in plasma and brain. (PubMed, Epilepsia) - "Based on these results, l-fenfluramine has more favorable properties than l-norfenfluramine for potential development as an enantiomerically pure medication. Although our findings are consistent with those previously reported for the MES test in mice and the scn1Lab-/- mutant zebrafish, they differ from those reported for the audiogenic seizures mouse model. Further studies, preferably in disease-specific models, would be desirable."

Journal • Preclinical • Anorexia • Cardiovascular • CNS Disorders • Epilepsy

Fenfluramine in refractory SCN1A-related 'genetic epilepsy with febrile seizures plus'. (PubMed, BMJ Case Rep) - "After treatment failure with sodium valproate, clobazam and topiramate, low-dose fenfluramine (2.2 mg/day, 0.15 mg/kg/day) achieved seizure freedom maintained for more than 1 year with no adverse effects. This dose is substantially lower than the 0.2-0.7 mg/kg/day used in Dravet syndrome trials, suggesting GEFS+ may require lower therapeutic thresholds."

Journal • CNS Disorders • Epilepsy • Pediatrics • Psychiatry

Neurologists' Views on the Management of Uncontrolled Epilepsy in Spain: A Preliminary Survey. (PubMed, Neurol Ther) - "There is a discrepancy between neurologists' treatment goals and their acceptance of persistent seizures in Spanish neurological practice. Several factors may be limiting the achievement of early seizure freedom, including short patient consultations and a lack of familiarity with new treatments, especially among epilepsy non-specialists. Addressing these barriers could improve outcomes for people with uncontrolled epilepsy."

Journal • CNS Disorders • Epilepsy

Fenfluramine Attenuates Retinal Microglial Activation but Does Not Rescue Structural and Vascular Deficits in a Rat Model of Dravet Syndrome. (PubMed, Int J Mol Sci) - "Electroretinography (ERG) showed selectively reduced oscillatory potential amplitudes, suggesting dysfunction of neurovascular coupling. Fenfluramine, an approved anti-seizure drug for DS, attenuated microglial activation but failed to rescue retinal structural or vascular deficits, indicating a dissociation between its anti-inflammatory and disease-modifying effects. Our findings suggest that multimodal retinal assessment could serve as a noninvasive biomarker platform for monitoring disease progression and therapeutic response in DS."

Journal • Preclinical • CNS Disorders • Epilepsy • Inflammation

The FINTEPLA as an Anti-SUDEP Therapy in Dravet Syndrome Project (clinicaltrials.gov) - P4 | N=25 | Recruiting | Sponsor: The University of Texas Health Science Center, Houston | Not yet recruiting ➔ Recruiting

Enrollment open • CNS Disorders • Epilepsy

Efficacy of fenfluramine in a pediatric epilepsy patient with a pathogenic SV2A variant: A case report. (PubMed, Epileptic Disord) - "We propose that FFA's effectiveness stems from its ability to address two core pathologies of SV2A deficiency: correction of the excitatory/inhibitory imbalance by restoring inhibitory tone through its serotonergic mechanism, and mitigation of neuroinflammation, thereby stabilizing the neuronal network. FFA may represent a promising therapeutic option for patients with SV2A variant-associated epilepsy, particularly those with a fever-sensitive, drug-refractory phenotype; however, further studies with larger case series are needed to confirm its efficacy."

Journal • CNS Disorders • Epilepsy • Inflammation • Pediatrics

Sustained seizure freedom with fenfluramine for refractory epilepsy due to 7q32-q34 deletion syndrome. (PubMed, Epileptic Disord) - No abstract available

Journal • CNS Disorders • Epilepsy