Rationale:
Dravet syndrome is a rare, drug-resistant epilepsy that usually presents within the first year of life. Dravet syndrome manifests in otherwise healthy infants and is often linked to SCN1A gene mutations that result in multiple seizure types, motor deficits, and cognitive and behavioral problems. Stiripentol is approved in the US for patients 6 months or older (weighing 15 lb or more) taking Clobazam. Prior to this approval, stiripentol was available through compassionate use until April 2019. While stiripentol has been marketed in Europe since 2007, information regarding US Prescribing practices has been limited. To identify and better understand the real-world utilization of stiripentol in the US, an analysis was performed.
Methods:
A retrospective analysis was performed, looking at data from historical records and current US Stiripentol prescribing practices as reported by a singular specialty pharmacy. Data was collected from April 2019 to September 2023. All data in the analysis were without patient identifiers, and included age, weight, dosage, specific dosing titration schedules, discontinuations, dosage at time of discontinuation, as well as concomitant medications as reported by caregiver conversations with specialty pharmacist. Demographic and dosing data collected were based upon the last prescription filled. Concomitant drugs were captured during the specialty pharmacy’s discussions with patients. The start and end dates were either the date the specialty pharmacy captured the data or patient-reported dates.
Results:
Dosing data was analyzed in all US patients ages: less than 1 to 53 years old receiving least one dose one dose of Stiripentol. Some patients were excluded from the analysis because of incomplete dosing data or missing weight information to calculate the daily dose. The overall average dose was 33.98 mg/kg/day, which is further broken down in Table 1.
The median starting dose at initiation was
27.55 mg/kg/d. The median second dose was
29 mg/kg/d, and the median maintenance dose (or last dose prescribed) was
32.46 mg/kg/d. From April 30, 2019 to May 5, 2023, 36% of patients that were initiated on stiripentol, discontinued therapy. The median last dose at time of discontinuation was
34.67 mg/kg/d. From July 2022 through July 2023 the most reported reason for discontinuation was adverse event (AE). The most reported AE during this period was lack of efficacy. ~ 12% patients that discontinued Stiripentol from July 2022- July 2023, restarted therapy. As of August 23, 2023: 45% of patients treated with Stiripentol at that time were not on concomitant Clobazam.
Conclusions:
This analysis of prescription data collected provides several new insights. Most prescription doses were lower than the approved dosing for stiripentol of
50 mg/kg/day (Max
3000 mg/day). It was also reported that almost half of patients (45%) that are currently taking Stiripentol are not taking concomitant Clobazam. This analysis can supplement the current label and provide more granular guidance for dosing, utilization, and titration to US prescribers of Stiripentol.
Funding:
Biocodex, Inc.