Prescription Records Reveal New Insights Into Stiripentol Use for Dravet Syndrome


Notably, nearly 50% of patients prescribed the Biocodex therapy were not on concomitant clobazam, a contrasting practice with the FDA label’s indication. To date, no data support its use as monotherapy for Dravet syndrome.

Gabrielle Stires, APRN-CNP, associate medical director at Biocodex

Gabrielle Stires, APRN-CNP

Based on data from a retrospective analysis of historical and current records of US prescribing practices from a singular specialty pharmacy, prescriptions of stiripentol (Diacomit; Biocodex) tended to be lower than the approved dose level, with almost half those prescribed were not also taking concomitant clobazam.1

Stiripentol was approved by the FDA in 2018 and was available via compassionate use up until 2019, and the indication was expanded in 2022 to include the treatment of seizures associated with Dravet syndrome (DS) in individuals aged 6 months of age or older who weigh 15 pounds or more, and who are also being treated with clobazam. Notably, no clinical data yet support the use of stiripentol alone in DS.

Dosing data were analyzed in all US patients who were younger than 1 year old or under 54 years of age who received least 1 dose of stiripentol (n = 596). All told, 45% (n = 267) of those included in the data were not also taking concomitant clobazam, while 55% (n = 329) were.

Gabrielle Stires, APRN-CNP, associate medical director at Biocodex, and colleagues presented the data in a poster at the 2023 American Epilepsy Society (AES) annual meeting, held December 1-5, in Orlando, Florida. “While stiripentol has been marketed in Europe since 2007, information regarding US prescribing practices has been limited. We report on an analysis conducted to identify and understand the real-world use of stiripentol in the United States,” they wrote.1

“This analysis can supplement the current label and provide more granular guidance for dosing, utilization and titration to US prescribers of stiripentol,” Stires et al concluded.

The approved dose of stiripentol is 50 mg/kg per day, to be administered by mouth in 2 or 3 divided doses,2 though the average overall dose in this analysis was revealed to be 33.98 mg/kg per day (range, 3.17-125.94) among the 12,168 doses dispensed in the records. At the initiation of treatment, the median starting dose was 27.55 mg/kg per day, which increased to 29 mg/kg per day for the median second dose. The median maintenance dose (or last dose prescribed) identified was 32.46 mg/kg per day.

Overall, from April 30, 2019, to May 5, 2023, a total of 36% (263 of 738) of those who initiated stiripentol ultimately discontinued therapy. From July 2022 to July 2023, the most reported reason for discontinuation of the anticonvulsant was a lack of efficacy, with roughly 12% of patients restarting the treatment later on.

READ MORE: Adjuvant Cenobamate Shows Significant Reductions in Seizures and Hospitalizations in Severe Refractory Epilepsy

Stiripentol operates by inhibiting GABA reuptake and producing a barbiturate-like positive allosteric modulation of GABAA receptors.3 Its pharmacokinetic properties have been assessed in a number of animal models already, and additional preclinical data presented at AES 2023 by Alexandre Bacq, PhD, a pharmacology researcher at Biocodex, and colleagues suggest that it may also have a compelling effect against epilepsy-related death, either sudden unexpected death in epilepsy (SUDEP) or following prolonged refractory status epilepticus (SE).4

“In Dravet syndrome, the effect of stiripentol on SUDEP rates is not described, but its preventive effect against prolonged SE is demonstrated, notably in the youngest patients. Future studies will evaluate the mechanisms of action of stiripentol explaining its effects against epilepsy-related mortality,” Bacq and colleagues wrote. They assessed the treatment's effects in 2 murine models: a 'DBA/2 SUDEP model’ and a ‘methionine sulfoximine (MSO)-induced SE’ model.

Clincial Takeaways

  1. A retrospective analysis of US prescribing practices revealed 45% of patients on stiripentol (Diacomit; Biocodex) were not prescribed concomitant clobazam.
  2. The average dose was 33.98 mg/kg per day, lower than the approved 50 mg/kg per day.
  3. Stiripentol's preclinical data also suggests a potential effect against epilepsy-related death, like SUDEP, but clinical studies are needed to confirm this.

In the DBA/2 SUDEP model, stiripentol was shown to prevent wild-running tonic-clonic seizures as well as associated death in a dose-dependent manner. In that model, audiogenic seizures were induced 30 minutes post systemic administration of stiripentol, and upon reaching optimal concentration (75 mg/kg), tonic seizures were prevented for a range of 30 minutes to 4 hours, and death was prevented for up to 2 hours.

In the MSO-induced SE model, SE began 4 hours after intraperitoneal MSO administration. Bacq and colleagues reported a progressive increase of the Racine score to 5.5 (±0.2) and mortality (84%) at the 8th hour. A single administration of 200-, 300-, and 400-mg/kg stiripentol 30 minutes pretreatment inhibited MSO-induced seizures, with Racine scores of 5.1 (±0.5), 3.1 (±0.4), and 1.4 (±0.6), respectively. Additionally, the respective percentages of death were 70%, 30% and 0% with those dose levels. MSO also strongly increased ammonia level, while stiripentol 300 mg/kg significantly reduced MSO-induced hyperammonemia, without effect in the control group, which reported normal ammonemia level.

Click here for more coverage of AES 2023.

1. Stires G, Fong V, Garcia F, Schad C. Real World Utilization of Stiripentol by United States (US) Prescribers: An Update. Presented at: AES Annual Meeting; December 1-5, 2023; Orlando, FL. Abstract 3.422.
2. Diacomit (stiripentol). FDA. Revised August 2018. Accessed December 4, 2023.,207223s000lbl.pdf
3. Aronson JK, Meyler L. Meyler’s Side Effects of Drugs: The International Encyclopedia of Adverse Drug Reactions and Interactions. Elsevier Science.2016:497-498. doi:10.1016/B978-0-444-53717-1.01471-2
4. Bacq A, Robert A, Cloarec P, et al. Stiripentol Efficacy Against SUDEP and SE-associated Mortality. Presented at: AES Annual Meeting; December 1-5, 2023; Orlando, FL. Abstract 1.271
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