Dravet Syndrome Medication Stiripentol Effective in Real World Settings Across Various Patient Profiles

New data from the STIRUS study indicate that real-world treatment with stiripentol (Diacomit; Biocodex) was linked to reduced seizure burden, fewer status epilepticus episodes, and lower healthcare utilization in patients with Dravet syndrome (DS), with benefits observed across age groups and co-medication patterns.¹

Presented at the 2025 American Epilepsy Society (AES) Annual Meeting, held December 5-9 in Atlanta, Georgia, the analysis comprised 98 patients with a confirmed DS who initiated stiripentol after August 2018 and received it for at least 3 months following. In this retrospective, observational study, data was extracted 3 months prior to treatment initiation, the first 3 months of treatment, and the final 3 months of stiripentol, irrespective of treatment discontinuation.

Led by Elaine Wirrell, MD, director of pediatric epilepsy at Mayo Clinic, treatment with the FDA-approved medication led to significant reductions in bilateral convulsive seizures (BCS; OR, 2.16; 95% CI, 1.25-3.75; P <.006). In addition, investigators found that the number of patients experiencing status epilepticus (SE) decreased from 33 at baseline to 16 and 14 during the first and final 3 months, respectively (ORs, >2.8; P <.003). Overall, the longest episode lasted a median of 15 minutes.

Stiripentol, an antiseizure medication, was approved by the FDA in 2018 and was available via compassionate use up until 2019. The indication was expanded in 2022 to include the treatment of seizures associated with DS in those 6 months of age or older who weight 15 pounds or more, and who are also being treated with clobazam. The therapy is designed to enhance GABAergic transmission through multiple mechanisms: positive allosteric modulation of GABA_A receptors, increased GABA levels by inhibiting its degradation, and inhibition of CYP-mediated metabolism of other antiseizure medications.

Coming into the STIRUS study, 94 of the 99 patients had an SCN1A mutation, and 90% experienced BCS. At baseline, patients were taking a median of 3 antiseizure medications, most commonly clobazam (n = 80), cannabidiol (n = 45), valproate (n = 42), fenfluramine (n = 24), or levetiracetam. In addition, the median age at DS diagnosis was 15 months, and the median age for initiating stiripentol was 6.9 years. Other baseline characteristics showed that 34% had SE, with the longest episode lasting a median of 30 minutes.

In addition to reductions in BCS, treatment with stiripentol led to reduced need for rescue medications (OR, 3.5; P <.0001) and seizure-related ER visits/hospitalizations (OR, 4.0; P <.0001 in the final 3 months). More notably, these improvements seen across patients were observed in a number of different age groups and regardless of stiripentol dosage or concomitant clobazam or valproate use.

The real-world study revealed quality of life improvements for 52% of patients and 54% of caregivers. In terms of safety, adverse events were found in 50% of patients, most commonly somnolence and decreased appetite, with no unexpected safety concerns.

At the 2024 AES Annual meeting, a product theater session focused on the impact of DS, signs and symptoms of the disease, as well as the importance of early intervention. One presentation, given by James Wheless, MD, FAAP, FAAN, FAES, highlighted the therapeutic utility of stiripentol, one of the longest standing therapies to treat DS. During the meeting, Wheless, professor and chief of pediatric neurology and the Le Bonheur Chair in Pediatric Neurology at the University of Tennessee Health Science Center, gave an overview of stiripentol and its use.

In the clip below, Wheless discussed his presentation from AES 2024, including the importance of proper administration of stiripentol, particularly when taking the medication with food to avoid degradation in the stomach. Wheless also talked about potential improvements to the drug’s delivery, such as developing a ready-to-use liquid or extended-release formulation to simplify dosing.

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REFERENCE
1. Wirrell E, Wheless J, Perry MS, et al. Real-World Use and Effectiveness of Stiripentol in U.S. Patients with Dravet Syndrome: Results from the STIRUS Study. Presented at: 2025 AES Annual Meeting; December 5-9; Atlanta, GA. Abstract 1.386