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

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

Development of a preclinical testing platform for clinically relevant therapy for Dravet syndrome. (PubMed, Epilepsia) - "This research lays the groundwork for exploring effective add-on compounds to clobazam and valproic acid in treating Dravet syndrome. The study further highlights the utility of the Scn1aA1783V/WT mice in discovering therapies for Dravet syndrome-associated pharmacoresistant seizures."

Journal • Preclinical • CNS Disorders • Epilepsy

A multielectrode array reveals therapeutic potential of translocator protein ligands in a zebrafish model of Dravet syndrome. (PubMed, J Pharmacol Exp Ther) - "The MEA assay was validated in wild-type ZF using pentylenetetrazol and Scn1Lab mutants using PK11195 and stiripentol...Current methodologies for drug discovery in larval zebrafish are limited in throughput and are highly invasive. We optimized and validated a higher throughput methodology for seizure detection in Scn1Lab mutants, identifying translocator protein, a mitochondrial protein, as a potential therapeutic target for developmental and epileptic encephalopathies."

Journal • CNS Disorders • Epilepsy • NAV1

Stiripentol prevents lethal audiogenic seizures in two mouse strains, relevant for SUDEP prevention. (PubMed, Epilepsy Behav) - "These findings suggest that STP exerts direct effects in preventing seizures and SUDEP in the two preclinical models studied. The observed plasma and brain concentrations of STP are compatible with the involvement of multiple mechanisms in its protective effects against seizures and SUDEP."

Journal • Preclinical • CNS Disorders • Epilepsy

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

NUDT21 lactylation reprograms alternative polyadenylation to promote cuproptosis resistance. (PubMed, Cell Discov) - "Notably, combined targeting of the lactate-NUDT21-FDX1-cuproptosis axis with the clinical LDHA inhibitor stiripentol and the copper ionophore elesclomol synergistically suppressed tumor growth. Collectively, our work identifies lactylated NUDT21 as a critical factor linking cellular metabolism to APA and proposes a promising therapeutic strategy for ESCC treatment."

Journal • Esophageal Cancer • Esophageal Squamous Cell Carcinoma • Oncology • Squamous Cell Carcinoma • AARS1 • CPSF6 • FDX1 • HDAC2 • LDHA • NUDT21

A phase 2 trial of stiripentol in patients with chemoresistant peritoneal metastatic carcinoma. (IGCC 2025) - P2 | "Stiripentol was safe for cancer therapy with immune-targeted chemotherapy. Its effect as resensitizer for chemotherapy needs more trials."

Clinical • Metastases • P2 data • Hematological Disorders • Oncology • Thrombocytopenia • LDHA

Efficacy of Stiripentol Beyond Dravet Syndrome: A Retrospective Medical Record Review of Patients with Drug-Resistant Epilepsies. (PubMed, Neurol Ther) - "Add-on stiripentol provides overall improvement in different seizure types and non-seizure manifestations for paediatric patients with drug-resistant epilepsy, including epileptic syndromes besides DS, and appeared effective in acute treatment of SE. Stiripentol was generally well tolerated."

Journal • Retrospective data • CNS Disorders • Epilepsy • Pediatrics

Cannabidiol metabolism in vitro: the role of antiseizure medications and CYP2C19 genotypes. (PubMed, Xenobiotica) - "CBD depletion in pooled human liver microsomes was studied at varying concentrations (400-6000 nM) in the absence and presence of valproic acid, clobazam, stiripentol and topiramate. Projected decreases in CBD CLint values when combined with several antiseizure medications simultaneously suggest a possibility drug-drug interaction potential to clinical relevance. A 1.3- to 4.8-fold increased exposure to unbound systemic CBD concentrations was predicted when combined with these antiseizure medications."

Journal • Preclinical • CNS Disorders • Epilepsy • CYP2C19

Long-term safety and effectiveness of fenfluramine in children and adults with Dravet syndrome. (PubMed, Epilepsia) - "Our OLE study of FFA in patients with DS confirmed previous positive findings and extended the exposure up to 3.5 years. No new or unexpected safety signals were observed and FFA demonstrated sustained and clinically meaningful reduction in MCSF."

Journal • Cardiovascular • CNS Disorders • Epilepsy • Heart Failure • Hypertension • Infectious Disease • Influenza • Otorhinolaryngology • Pulmonary Arterial Hypertension • Pulmonary Disease • Respiratory Diseases • CSF1

A Stratified Analysis of Efficacy and Safety of Fenfluramine in Patients With Dravet Syndrome (AAN 2025) - "FFA was evaluated in three pivotal phase 3 RCTs and is approved for the treatment of seizures associated with DS in the United States, European Union, United Kingdom, Japan, and Israel in patients ≥2 years of age.Design/Patients (aged 2-18y) with DS treated with placebo, 0.2 or 0.7 mg/kg/d FFA (0.2FFA, 0.7FFA) without stiripentol (STP), or 0.4 mg/kg/d FFA with STP (0.4FFA+STP) were included. FFA is associated with improved seizure and non-seizure outcomes relative to placebo, regardless of age, severity, or SCN1A status. Inferential analyses of stratified groups in larger populations may provide a better understanding of the benefits seen with different DS populations, concomitant medications, and FFA doses."

Clinical • Alzheimer's Disease • CNS Disorders • Cognitive Disorders • Epilepsy • CSF1

Impact of Fenfluramine on Convulsive Seizure Frequency in Dose-Capped Patients With Dravet Syndrome (AAN 2025) - P3 | "At RCT completion, patients were re-initiated with fenfluramine 0.2 mg/kg/day for 4 weeks, and then titrated to effect and tolerability with a maximum dose of 0.7 mg/kg/day (maximum 26 mg/day) or 0.4 mg/kg/day (maximum 17 mg/day) with concomitant stiripentol. Patients weighing ≥37.5 kg and receiving the maximum daily dose of fenfluramine (i.e., dose-capped) experienced similar MCSF change from RCT baseline as patients who were not dose-capped."

Clinical • CNS Disorders • Developmental Disorders • Epilepsy • CSF1

Pharmacokinetic variability and use of therapeutic drug monitoring of cannabidiol in patients with refractory epilepsy. (PubMed, Epilepsia) - "This observational study with TDM data revealed extensive pharmacokinetic variability of CBD in patients with refractory epilepsy. The results demonstrate the need for close follow-up and use of TDM, including biochemical markers of toxicity, for individualized treatment with CBD."

Journal • PK/PD data • CNS Disorders • Epilepsy

Safety and effectiveness of stiripentol in patients with Dravet syndrome: A prospective, 3-year, postmarketing surveillance study. (PubMed, Dev Med Child Neurol) - No abstract available

Journal • P4 data • CNS Disorders • Epilepsy

Metabolic Activation of Stiripentol Correlates with Cytotoxicity. (PubMed, Chem Res Toxicol) - "Stiripentol (SRP) is an antiepileptic agent utilized in managing seizures related to Dravet syndrome. Pretreatment with ketoconazole, a selective CYP3A enzyme inhibitor, mitigated the susceptibility of hepatocytes to SRP-induced cytotoxicity. These findings suggest that SRP may undergo metabolism to the α,β-unsaturated ketone metabolite, potentially contributing to the cytotoxic effects associated with SRP."

Journal • Ataxia • CNS Disorders • Epilepsy • Movement Disorders

Safety and effectiveness of stiripentol in patients with Dravet syndrome: A prospective, 3-year, postmarketing surveillance study. (PubMed, Dev Med Child Neurol) - "In real-world clinical settings, long-term STP treatment can be safe and effective in patients with Dravet syndrome."

Journal • P4 data • CNS Disorders • Epilepsy

From barbiturates to ganaxolone: The importance of chirality in drug development and in understanding the actions of old and new antiseizure medications. (PubMed, Pharmacol Ther) - "Out of 37 antiseizure medications (ASMs) currently in the market, 17 are chiral molecules and an additional one (oxcarbazepine) is a prodrug of the chiral compound licarbazepine. Of the 17 chiral ASMs, six (ethosuximide, fenfluramine, methsuximide, mephobarbital, stiripentol and vigabatrin) are marketed as racemates, and the remainder are licensed as enantiomerically pure medicines...We identified a number of critical knowledge gaps that are relevant to the use of chiral drugs in epilepsy, including a remarkable lack of published information on the comparative pharmacokinetics, toxicity and antiseizure activity of the enantiomers of most racemic ASMs. The importance of chirality aspects in understanding the clinical actions of racemic ASMs is discussed, together with the rationale for the development of enantiomerically pure follow-up compounds with potentially improved efficacy, safety and commercial viability."

Journal • Review • CNS Disorders • Epilepsy

Isolated kidney transplantation in an adolescent on Lumasiran therapy for Primary Hyperoxaluria type 1 (IPNA 2025) - "Aims/Purpose Primary hyperoxaluria type 1 (PH1) is a rare inherited disorder of glyoxylate metabolism resulting in overproduction and deposition of oxalate in end-organs, lead ing to kidney failure and systemic oxalosis. We provide and discuss details of peri-transplant management to reduce POx with pre-emptive dialysis. We highlight the importance of confirming long-term access to siRNA therapy and discuss contingency plans ahead of transplant, including additional strategies such as the use of Nedosiran, Stiripentol and Tolvaptan."

Genetic Disorders • Nephrology • Transplantation

Treatment of Dravet disease and false urine testing with ecstasy: a little-known interference (PubMed, Ann Biol Clin (Paris)) - "The presence of ecstasy in the first 2 samples was not confirmed by gas chromatography-mass spectrometry, which identified stiripentol in all 3 urines...These concentrations explain the false positives in the first two urine samples, and the negative result in the last. This work underlines the need to remain critical of the results of immuno-screening methods, and to confirm them with a reference method."

Journal • CNS Disorders • Epilepsy

An adult case of Dravet syndrome in which seizures worsened after discontinuation of lamotrigine and administration of stiripentol (PubMed, Rinsho Shinkeigaku) - "Lamotrigine, which had been taken at the time of diagnosis, was discontinued and stiripentol was administered, but the seizure frequency worsened. Because of the pathology of Dravet syndrome in adults may differ from that in children, care must be taken when selecting antiepileptic drugs."

Journal • CNS Disorders • Epilepsy

Use of Cenobamate in Dravet Syndrome – Report of Four Cases (AES 2024) - "CNB was then added to divalproex, clobazam, and fenfluramine and titrated over 12 months to 200mg daily...CNB was then added to oral diazepam and was slowly titrated to 100 mg daily...CNB added to valproic acid, clobazam, and stiripentol, and was gradually titrated to 100 mg daily...CNB was added to her regimen of divalproex, clobazam and levetiracetam and titrated to 50 mg daily gradually... This case series suggests that CNB might be an effective alternative for the treatment of seizures in DS patients without serious side effects. Three of our patients from different age groups experienced significant improvement in their seizure control after addition of CNB. For one of our patients, response to therapy seemed to be transient and CNB dose titration was limited by side effects."

Clinical • CNS Disorders • Epilepsy

Stiripentol Use in Dravet Syndrome Patients in the USA (AES 2024) - "Funding: This study was sponsored by Biocodex Rationale: Stiripentol (STP) was approved in August 2018 by the US FDA and is currently indicated "for the treatment of seizures associated with Dravet syndrome in patients taking clobazam who are 6 months of age and older and weighing 7 kg or more". The STIRUS study will provide real world evidence of post-marketing utilization of STP utilization in the US. In addition, this study will provide continued evidence of the management of Dravet Syndrome patients for intervals of greater than 10 years; including those US patients treated with STP before and after US marketing authorization."

Clinical • CNS Disorders • Epilepsy

Results of a Long-Term Post-Marketing Surveillance Study on Stiripentol Safety and Efficacy in a Large Cohort of Japanese Patients (AES 2024) - "The present analysis reports the largest cohort of patients in a real-world setting, followed for 3 years. Here, we did not identify new adverse drug reactions and confirmed the long-term efficacy of STP in decreasing tonic-clonic/clonic seizures. Additionally, we report efficacy of stiripentol on focal impaired awareness seizures as well as generalized myoclonic/generalized atypical absence seizures."

Clinical • P4 data • Absence Seizure Disorder • Anorexia • Biliary Cancer • CNS Disorders • Epilepsy • Hepatology • Liver Failure • Oncology • Solid Tumor

Results of DIAVEY, the European Post-Marketing Safety Study on Stiripentol Use (AES 2024) - "16 DS patients were less than 1 year-old, and 46 were between 1 and 3 years of age.At stiripentol start, 79% of DS patients were receiving valproate, 71% clobazam, and 24% topiramate, while 56% of non-Dravet patients were receiving clobazam, 36% valproate, and 25% carbamazepine. DIAVEY didn't identify new ADRs, and only thrombocytopenia was added in the SmPC. Lack of efficacy and/or ADRS were the main reasons for stiripentol discontinuation, which occurred more frequently in non-Dravet patients or when stiripentol dosage was notably lower than the 50 mg/kg/day recommended dose."

Clinical • P4 data • CNS Disorders • Epilepsy • Fatigue • Hematological Disorders • Hepatology • Neutropenia • Thrombocytopenia

Mood and Behavioral Adverse Events of Antiseizure Medications as a Surrogate Marker for Assessing the Risk of Antiseizure Medication Related Suicidality (AES 2024) - "Increased risk of suicidality was associated with 8 out of 11 ASMs, with topiramate (TPM) and lamotrigine (LTG) reaching statistical significance...A case-controlled study published in 2010 indicated that newer ASMs (levetiracetam (LEV), tiagabine, (TGB), vigabatrin (VGB) and TPM) are associated with a high potential to cause depression, leading to a 3-fold increase in risk of suicidal behavior as compared to no use over the past year (Andersohn 2010)... : There is a significant information gap regarding the incidence of mood and behavioral adverse events reported in the PIs. We are continuing to collect data on the risk of ASM related suicidality."

Adverse events • CNS Disorders • Depression • Epilepsy • Mood Disorders • Psychiatry • Suicidal Ideation