Medical Affairs Biocodex, Inc San Mateo, California
Rationale: Dravet syndrome is a rare, drug-resistant epilepsy that first 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. Although available in Europe since 2007, stiripentol has only been available in the U.S. under Compassionate Use until March 2019, when it became commercially available. The FDA approved stiripentol in 2018 for the treatment of seizures associated with Dravet syndrome in individuals older than two years taking clobazam. This analysis was done to provide an overview of current U.S. stiripentol-dosing practices for this rare syndrome, which had no specific ICD-10 diagnostic code during this period. Methods: Retrospective analysis of data from the single specialty pharmacy dispensing stiripentol from April 29, 2019 to April 30, 2020. All data meeting specified criteria were included in the analysis without patient identifiers; these criteria included at least two fills (initial and latest), gender, age, weight, prescriber state, diagnosis code, status (naïve/transition from Compassionate Use) and specific dosing instructions. Results: The sample consisted of 740 prescriptions for 370 individuals who were 47% female with an average age of 12.5 years (±7.2, range 1.0-38.0) and average weight of 40.4 kg (± 1.5; range 9.5-113.4). Of these, 235 were new to stiripentol and 135 transitioned from Compassionate Use. Titration within the first month was seen in 21% of naïve and 2% of transition patients. The average dose of the latest prescription was 35 mg/kg/day for naïve and 28 mg/kg/day for transition patients. The most common dosing frequency was two times per day (76%) with three times (22%), once (2%), and four times per day (0.5%) being much less common. A total of 44 ICD-10 codes were recorded in seven categories, the most common (93.5%) being Epilepsy and Recurrent Seizures (G40 codes), specifically G40.409 (45%), G40.309 (21%), and G40.319 (6.5%). The average dose prescribed is presented in Table 1 for all patients and prescriptions, broken out by naïve/transition status and initial/latest prescription. Table 2 presents data from the latest prescription grouped by dose ranges, showing that 72% of prescriptions were written for 39 mg/kg/day or less. Dose (mg/kg/day) by age group showed higher average doses in the 1–10 year age group (39 ± 19) than in either the 11–19 year group (25 ± 14) or the 20-38 year group (23 ± 12). Conclusions: This analysis of prescription data during the first year of transition from Compassionate Use following FDA approval provides several insights. First, the wide variety of ICD-10 codes reflects the lack of syndrome specific coding. New ICD codes for Dravet syndrome have been approved and will go into effect on October 1, 2020. Second, although the recommended dosing for stiripentol is 50 mg/kg/day in two or three divided doses, U.S. physicians progressively decrease mean stiripentol dose as patient age increases, mirroring the current practice in Europe and Japan. Funding: Please list any funding that was received in support of this abstract.: This analysis was funded by Biocodex, Inc. Click here to view image/table
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