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

Repurposed Stiripentol Disrupts the Lactate Driven AARS1 Mediated VDAC1 Lactylation Feed Forward Loop in CIH Exacerbated Fibrosis (ERS 2026) - "Background: Obstructive sleep apnoea associated chronic intermittent hypoxia, CIH, often coexists with interstitial lung disease and is linked to faster fibrosis progression, but mechanisms remain unclear.Aims: We tested whether CIH driven lactate is sensed by AARS1 to catalyse VDAC1 lactylation, triggering mitochondrial injury and a feed forward rise in glycolysis and lactate that drives alveolar type II, AT2, senescence and fibrosis, and whether repurposed stiripentol blocks this pathway. C57BL 6J mice received intratracheal bleomycin, 2.5 mg per kg, then CIH, 5 to 21 percent oxygen cycles, 8 hours per day for 8 weeks. A lactate sensing AARS1 VDAC1 lactylation feed forward loop links CIH to mitochondrial dysfunction, AT2 senescence and worsened fibrosis and is druggable with repurposed stiripentol."

Fibrosis • Immunology • Interstitial Lung Disease • Metabolic Disorders • Pulmonary Disease • Respiratory Diseases • Sleep Apnea • Sleep Disorder • AARS1 • CDKN1A • VDAC1

Potential Role of CYP3A4 in Determining In Vivo Exposure to Cannabidiol (CBD) and its Active Metabolite 7-OH-CBD: Evidence from an In Vitro Study. (PubMed, Eur J Drug Metab Pharmacokinet) - "ASMs with CYP3A4-inhibitory potential may alter systemic exposure to both CBD and its active metabolite, 7-OH-CBD, as demonstrated in vitro. However, co-administration of CBD with CYP3A4-substrate ASMs or CYP2C19 inhibitors is predicted to result in only modest increases in CBD exposure."

Journal • Preclinical • CNS Disorders • Epilepsy • CYP2C19 • CYP2C9 • CYP3A4

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

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

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

Histone Lactylation in Cancer-Associated Fibroblasts Induces Extracellular Matrix Remodeling and Immunosuppression to Promote Colorectal Cancer Progression. (PubMed, Cancer Res) - "Stiripentol, a clinical drug that targets lactylation, potentiated the efficacy of immunotherapy in CRC models. Together, this study demonstrates that elevated lactate levels in CAFs reprogram the epigenetic landscape to promote tumor progression and immunosuppression, highlighting the potential of targeting CAF histone lactylation as a therapeutic strategy for CRC."

Journal • Colorectal Cancer • Oncology • Solid Tumor • CAFs • CD8 • LDHA • NPM1 • RHOA • TGFB1

Acute effects of anti-seizure medications on network level dynamics: A systematic comparison using multielectrode arrays. (PubMed, Epilepsia) - "Several limitations should be considered, including the use of primary neuron cultures, incomplete maturation of certain drug targets, evaluation of only acute drug effects, and the limited spatial resolution of low-density MEA systems. Nevertheless, our results demonstrate that this MEA-based platform enables systematic evaluation of ASM effects on neuronal networks under identical experimental conditions. Furthermore, multivariate and unsupervised clustering analysis of 44 MEA parameters facilitated classification independent of drug mechanism of action. These findings suggest that MEA, combined with multidimensional data analysis, may provide a useful platform for the direct comparison of ASMs and could contribute to future pharmacological screening and drug discovery efforts."

Journal • CNS Disorders • Epilepsy

Optimizing polytherapy management for Dravet syndrome in the United States: A National Expert Consensus. (PubMed, Epilepsia Open) - No abstract available

Journal • CNS Disorders • Epilepsy

Integrated Radioproteomic Modeling for Early Recurrence Prediction and Metabolic Characterization in Hepatocellular Carcinoma. (PubMed, JCO Precis Oncol) - "This study bridges artificial intelligence-driven imaging and mechanism-guided therapy by developing a biologically interpretable DL model for HCC recurrence prediction. Radioproteomic integration identified dysregulated pyruvate metabolism as a hallmark of high-risk HCC, enabling the repurposing of stiripentol as a potential therapy. This framework suggests a potential strategy linking noninvasive risk stratification with pathway-guided treatment although further validation and prospective studies are needed to establish its clinical utility."

Journal • Hepatocellular Cancer • Oncology • Solid Tumor

Efficacy and adverse event profile of pharmacological and non-pharmacological therapies in Dravet Syndrome: a systematic review (EAN 2026) - "The most frequent treatments were fenfluramine, valproate, clobazam, and stiripentol, see Figure 1 Adjuvant therapies included cannabidiol/THC (19 patients) and a ketogenic diet (60 patients). Available evidence suggests that fenfluramine and ketogenic diet can reduce crisis in Dravet, with a minority achieving freedom from disease, while cannabinoids show variable answers. However, design heterogeneity, co-interventions and incomplete security report limit comparisons and robust meta-analysis. Studies with standardized structures are required and systematic follow-up of adverse events to better define risk-benefits."

Adverse events • Clinical • Review • CNS Disorders • Epilepsy

Prolonged fenfluramine use in open-label studies of Dravet or Lennox-Gastaut syndromes: Long-term safety, tolerability, patient global functioning, and considerations for interpreting effectiveness. (PubMed, Epilepsia) - P3 | "In our OLE study of patients with DS or LGS treated with fenfluramine (up to 4 years), no new or unexpected safety signals were observed; global functioning was improved or stable (vs. study baseline) in >90% of patients, supporting long-term fenfluramine use in pediatric and adult patients with DS or LGS."

Journal • CNS Disorders • Epilepsy • Pediatrics

Healthcare resource utilization and persistence in children and adults with Dravet syndrome receiving fenfluramine: a retrospective analysis using United States claims data. (PubMed, Seizure) - "High fenfluramine treatment persistence indicates that children and adults with DS tend to continue with fenfluramine treatment, regardless of their concomitant ASM regimen. Significant reductions in HCRU in were observed in individuals receiving fenfluramine ≥6 months; however, further research is warranted in this area."

HEOR • Journal • Retrospective data • CNS Disorders • Epilepsy

Epigenetic Silencing of RFX7 Defines a Transcriptional Axis Linking Lactate Metabolism to Immune Checkpoint Therapy in Glioblastoma. (PubMed, Adv Sci (Weinh)) - "Pharmacological inhibition of lactate production with Stiripentol reduced H4K12la level, intracranial tumor growth, and immunosuppressive cell infiltration, while improving survival and response to immune checkpoint based therapy in experimental models. These findings identify an upstream transcriptional pathway linking lactate metabolism, histone lactylation, and immune suppression in GBM. Targeting the RFX7-PIK3IP1 axis provides a mechanistic rationale for metabolic-immune modulation in therapy, addressing an aspect that has remained insufficiently understood in GBM immune resistance."

IO biomarker • Journal • Brain Cancer • Glioblastoma • Glioma • Immune Modulation • Immunology • Oncology • Solid Tumor • CSF1 • PD-L1 • PIK3IP1

Early-Onset and Syndromic Pediatric Epilepsy in Kazakhstan: Clinical, Molecular, and Phenotypic Spectrum. (PubMed, J Clin Med) - "Treatment response was frequently partial or poor, although selected genotype-linked treatment observations were noted in PRRT2 (carbamazepine), PNPO (pyridoxine), and one SCN1A case (stiripentol). This study expands the clinicogenetic characterization of pediatric epilepsy cases with clinically relevant or potentially relevant genetic findings in Kazakhstan and highlights the value of integrated molecular, phenotypic, and segregation analysis in underrepresented populations."

Journal • CNS Disorders • Developmental Disorders • Epilepsy • Metabolic Disorders • Pediatrics • Psychiatry

Employing zebrafish to understand genetic drivers of epilepsy-related comorbid behaviors. (PubMed, Front Pharmacol) - "Pharmacological testing revealed that, compared to stiripentol and valproic acid, clemizole produced the most extensive rescue of deficits in scn1lab mutants. Within the broader epilepsy research landscape, this study further supports the use of zebrafish as a robust, dual platform to understand and discover novel therapeutics for epilepsy and its associated behavioral comorbidities."

Journal • Alzheimer's Disease • CNS Disorders • Cognitive Disorders • Developmental Disorders • Epilepsy • Pediatrics

Stiripentol induces ER stress and pyroptosis in pancreatic cancer cells under metabolic stress by dysregulating SFAs/UFAs homeostasis. (PubMed, Cell Oncol (Dordr)) - "Our findings demonstrate that stiripentol disrupts SFAs/UFAs homeostasis, thereby inducing ER stress and pyroptosis in PDAC cells under serum deprivation condition. Notably, stiripentol has synergistic antitumour effects with GEM, highlighting its translational potential as a promising combination therapy for PDAC treatment."

Journal • Brain Cancer • Glioblastoma • Oncology • Pancreatic Cancer • Pancreatic Ductal Adenocarcinoma • Solid Tumor • FADS2

Bridging evidence gaps in dravet syndrome: real-world safety insights from under-reported antiseizure therapies. (PubMed, Expert Opin Drug Saf) - "While stiripentol, clobazam, fenfluramine, and cannabidiol are supported by the strongest evidence, less frequently reported therapies, including perampanel, topiramate, levetiracetam, cenobamate, and ketogenic dietary therapies, may benefit selected patients but require cautious use due to heterogeneous efficacy and safety data. The complexity of available options highlights the need for individualized, dynamic treatment strategies. Although emerging targeted and genetic therapies may represent a future paradigm shift beyond symptomatic seizure control, their clinical impact remains to be established, warranting careful implementation and long-term safety evaluation."

Journal • Real-world evidence • Review • CNS Disorders • Epilepsy • Gene Therapies

Lipid Nanoparticles with Stiripentol and Cannabidiol Oil: From Rational Optimization to Preclinical Characterization. (PubMed, Pharmaceutics) - "Both STP and CBD showed sustained release profiles and demonstrated oral pharmacokinetic profiles that were comparable or superior to current commercial products. This novel formulation represents a promising therapeutic alternative for DS, enabling the co-administration of STP and CBD while potentially enhancing CBD bioavailability and treatment adherence in pediatric populations."

Journal • Preclinical • CNS Disorders • Epilepsy • Pediatrics

Efficacy and safety of fenfluramine in Dravet syndrome; A monocentric, observational study focused on initial dose, blood concentration, and reduction of concomitant medications. (PubMed, Epilepsy Behav) - "FFA effectively reduced convulsive seizures in DS even at low concentrations. we recommend the initiation of low-dose FFA, which may allow dose reduction or discontinuation of concomitant antiseizure medications in FFA responders."

Journal • Observational data • Cardiovascular • CNS Disorders • Epilepsy • Heart Failure • Hypertension • Pulmonary Arterial Hypertension • Pulmonary Disease • Respiratory Diseases

Protein Adduction and Hepatotoxicity Induced by Stiripentol. (PubMed, Chem Res Toxicol) - "L-Buthionine-sulfoximine co-treatment potentiated the protein adduction and the susceptibility of hepatocytes to the cytotoxicity of STP. These findings suggest that protein adduction is responsible for STP-induced hepatotoxicity, and GSH serves a detoxification function against protein adduction."

Journal

Mitochondrial Dysfunction and Senescence Accompany Glioblastoma Cell Death Triggered by a Putative Metabolic Inhibitor. (PubMed, Eur J Pharmacol) - "In our previous study on GBM, we aimed at targeting the metabolic reprogramming of cancer by using stiripentol (STP), a putative lactate dehydrogenase (LDH) inhibitor and an FDA-approved anti-epileptic drug...The cellular changes were accompanied by an increase in reactive oxygen species, a decrease in mitochondrial membrane potential, and induction of senescence in GBM cells. Our research indicates that further research in senescence-inducing agents and novel LDH inhibitors can provide novel therapeutics for GBM."

Journal • Brain Cancer • Epilepsy • Glioblastoma • Metabolic Disorders • Oncology • Solid Tumor

Utilization of Stiripentol in Children With Developmental and Epileptic Encephalopathies: Considerations for Clinical Practice. (PubMed, Pediatr Neurol) - "Stiripentol is an antiseizure medication approved for the treatment of seizures associated with Dravet syndrome in children 6 months of age and older currently taking clobazam. The purpose of this paper is to review the available evidence of the efficacy and safety of stiripentol in children with non-Dravet DEEs. Practical considerations regarding the use of stiripentol in clinical practice to treat pediatric patients with DEE will also be discussed."

Journal • Review • CNS Disorders • Developmental Disorders • Epilepsy • Pediatrics • Psychiatry

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. 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