Diacomit (stiripentol) / Biocodex, Meiji Seika - LARVOL DELTA

Practical consensus recommendations for polytherapy involving stiripentol in Dravet syndrome: A nominal group approach. (PubMed, Epilepsia Open) - "Dravet syndrome is a rare and severe form of epilepsy that begins in early childhood, with seizures that often persist throughout life. Because the disease is highly drug resistant, most patients are treated with polytherapy, making clinical management complex for clinicians. This consensus brings together published evidence and expert experience to provide practical guidance on the management of polytherapy in Dravet syndrome, supporting clinicians in optimizing patient care."

Journal • CNS Disorders • Epilepsy

Lactylation as a metabolic-epigenetic switch in cancer: dual roles in cell death resistance and therapeutic vulnerability. (PubMed, Cell Death Dis) - "Critically, preclinical and clinical studies in validated models demonstrate that targeting this lactylation network (e.g., LDHA inhibition with stiripentol, KAT inhibitors, or site-specific blockers) yields striking synergistic effects, potentiating tumor sensitivity to chemotherapy, radiotherapy, and immunotherapy...This work not only establishes lactylation as a central mechanism of therapeutic resistance but also provides a novel conceptual paradigm for understanding how metabolic signals dynamically encode cancer cell vulnerabilities, offering transformative opportunities for precision oncology.Created in BioRender. Chengjiao, Y. (2026) https://BioRender.com/0lbu6jy."

IO biomarker • Journal • Review • Acute Lymphocytic Leukemia • Hematological Malignancies • Leukemia • Oncology • T Acute Lymphoblastic Leukemia • T-cell Acute Lymphoblastic Lymphoma • Thoracic Cancer • AARS1 • LDHA • TRIM33

Stratified Effectiveness and Safety of Fenfluramine in Dravet and Lennox-Gastaut Syndromes: A Retrospective Comparative Analysis of Trial and Open-label Extension Data (2018-2024) (AAN 2026) - "Results were descriptively compared across DS and LGS by age (<6 y, 6-17 y. ≥18 y) and stiripentol (STP) co-therapy by using IBMSPSS V 29. Fenfluramine provides durable seizure reductions and consistent safety across DS and LGS, with the strongest benefit observed in younger and STP-naïve patients. The absence of cardiac toxicity across ~1,000 patient-years supports its long-term safety. Stratified synthesis of multi-trial evidence enables precision use of FFA in developmental and epileptic encephalopathies."

Retrospective data • Cardiovascular • CNS Disorders • Epilepsy • Heart Failure • Pulmonary Arterial Hypertension • Respiratory Diseases • CSF1

Aars1-vdac1 Lactylation Feedback Loop Drives Alveolar Senescence in Chronic Intermittent Hypoxia-aggravated Pulmonary Fibrosis: Therapeutic Potential of Stiripentol (ATS 2026) - No abstract available

Immunology • Pulmonary Disease • Respiratory Diseases • AARS1 • VDAC1

Stiripentol directly attenuates immunosuppression of tumor-infiltrating myeloid cells to potentiate anti-PD-1 efficacy. (PubMed, BMC Cancer) - No abstract available

Journal • Oncology

Stiripentol: Unpublished results from the first phase 2 clinical trial in Lennox-Gastaut syndrome conducted in the early 1990s. (PubMed, Epilepsia) - "Although this study was conducted before standardized clinical trial designs for LGS were established, a more comprehensive evaluation of stiripentol could have provided further insight into its potential benefits in this severe developmental and epileptic encephalopathy."

Journal • P2 data • CNS Disorders • Epilepsy • Hematological Disorders

The Antiseizure Medication Stiripentol Inhibits Mitochondrial Complex I by Blocking Early-Stage Electron Transfer. (PubMed, J Biol Chem) - "These findings uncover a previously unrecognized mode of complex I inhibition and link stiripentol's metabolic effects to direct modulation of mitochondrial NADH oxidation. This work broadens the understanding of stiripentol's mechanism of action and highlights its potential to modulate redox metabolism in cancer cells."

Journal • CNS Disorders • Epilepsy • Oncology

From Symptomatic Therapies to Disease-Modifying Approaches for Neuronal Sodium Channel Disorders. (PubMed, Int J Mol Sci) - "Additionally, pharmacological agents such as fenfluramine, stiripentol, and cannabidiol, although not acting directly on sodium channels, represent recognized therapeutic options for SCN1A-related Dravet syndrome. This review summarizes recent advances in approved and investigational treatments for sodium channel-related neurological disorders, highlighting the transition from symptomatic to precision therapies."

Journal • Review • CNS Disorders • Epilepsy • Gene Therapies

Safety of Drugs Used in Difficult-to-Treat Epileptic Syndromes: A Disproportionality Analysis Using the Eudravigilance Database. (PubMed, Pharmaceuticals (Basel)) - " We retrospectively analyzed the publicly available data regarding Individual Case Safety Reports (ICSRs), presenting stiripentol, cannabidiol, or fenfluramine as suspected drugs, reported on the Eudravigilance database until the third quarter of 2024. Our analysis did not highlight new and unexpected serious safety signals but confirmed the need to strictly monitor patients for the risk of adverse events. However, further prospective studies are required to better clarify the safety profile of these drugs in order to optimize their use."

Journal • Cardiovascular • CNS Disorders • Epilepsy

Real-world disproportionality analysis of sleep disturbances associated with antiseizure medications in epilepsy: a pharmacovigilance study. (PubMed, Front Pharmacol) - "Significant signals were detected for sodium channel blockers eslicarbazepine, stiripentol, and cenobamate, as well as for mechanistically diverse agents vigabatrin, pregabalin, brivaracetam, and cannabidiol. The distinct disproportionality reporting profiles identified for some agents, which differ from prior evidence, necessitate careful clinical interpretation. Overall, this study elucidates the complex sleep safety profiles of ASMs, offering evidence to support more informed drug selection and monitoring in practice."

Adverse events • Journal • Real-world evidence • CNS Disorders • Epilepsy • Insomnia • Sleep Disorder

Psychiatric and behavioural side effects of antiseizure medications in epilepsy. (PubMed, J Neurol) - "PBSEs can often be anticipated, mitigated, and frequently reversed. A risk-stratified prescribing strategy-monotherapy first, enzyme-neutral or mood-friendly medications for vulnerable patients, folate supplementation for inducers, and early switch from offending agents-can safeguard mental health without compromising seizure control."

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

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

Stiripentol use in Dravet syndrome patients in the USA: Results of a real-world study. (PubMed, Epilepsia Open) - "The STIRUS study found that stiripentol, an anti-seizure medication specifically approved for Dravet Syndrome, helped reduce seizures and hospital visits for children living with this severe form of epilepsy. Patients had fewer convulsive seizures, needed fewer rescue medicines, and reported better quality of life. Despite these benefits, stiripentol is still not widely used and often started too late in treatment, suggesting earlier use could further improve outcomes."

Journal • Real-world evidence • CNS Disorders • Epilepsy

Physiologically Based Pharmacokinetic Modeling of Clobazam and Stiripentol Co-Therapy in Dravet Syndrome. (PubMed, J Pers Med) - "Extrapolation to pediatric patients under two years of age predicted CLB, N-CLB, and STP exposures that were comparable to older children and remained within their reported efficacy and safety margins, suggesting no major ontogeny-related effect on exposure. The PBPK model supports the safe extrapolation of CLB and STP co-administration to pediatric Dravet syndrome patients as young as six months."

Journal • PK/PD data • CNS Disorders • Epilepsy • Pediatrics • CYP2C19

Stiripentol Use in Lennox-Gastaut Syndrome: Results from a Phase 2 Clinical Trial (AES 2025) - "They received an average of 3 ASMs, most commonly valproate (n=10) and clobazam (n=8). Despite the small sample size, stiripentol appeared to reduce seizure burden in LGS patients. These promising results support further investigation in a larger, controlled trial."

Clinical • Late-breaking abstract • P2 data • Absence Seizure Disorder • CNS Disorders • Epilepsy • Gastroenterology • Gastrointestinal Disorder

Stiripentol Use in Dravet Syndrome Is Associated with Lower Mortality Rates in a Real-World United States (US) Cohort (AES 2025) - "STP has demonstrated efficacy in reducing seizure burden in DS through combating GTCS, preventing episodes of SE, and achieving seizure freedom during RCTs. This real-world analysis suggests a lower mortality risk among STP-treated patients compared to the reported annual DS mortality rate. Given the limited data on mortality outcomes associated with DS-approved ASMs, this analysis contributes valuable insight into STP's potential to reduce mortality risk in this high-risk population."

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

Efficacy and Tolerability of Stiripentol Across non-Dravet Developmental and Epileptic Encephalopathies: A Literature Review Including Genetic and Syndromic Epilepsies (AES 2025) - "STP demonstrates consistent efficacy and acceptable tolerability across a wide spectrum of non-Dravet DEEs, including ultra-rare genetic forms. Its effectiveness across seizure types and in RSE supports its consideration as a treatment option in complex drug-resistant epilepsy. Prospective, genotype-driven studies are warranted to better define the optimal use of STP in DEEs."

Clinical • Review • Anorexia • Ataxia • CNS Disorders • Epilepsy • Movement Disorders

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

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

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