Abstracts

Rationale: br>Dravet syndrome (DS) is a rare childhood developmental epileptic encephalopathy often characterized by unpredictable and treatment-resistant seizures. Current options are mostly generic anti-seizure medications (ASMs), with few solely indicated for DS. This study aimed to characterize the real-world global treatment patterns and burden associated with DS.

Methods:
A retrospective analysis using data from the real-world Adelphi DS Disease Specific Programme (DSPTM) was conducted. Neurologists and pediatric neurologists in France, Germany, Italy, Spain, UK, USA, China and Japan completed cross-sectional surveys for their next consecutive patients with DS from July 2022. Information collected included demographics, clinical details, treatment journey including reasons for treatment discontinuation, AEs, and clinical and humanistic outcomes such as impact of AE on quality of life (QoL). Descriptive analyses were performed to describe the treatment burden. Patients receiving orphan drugs specifically indicated (ODSI) for DS were identified. Data from France and Japan were from an interim data cut (April 7, 2023); other data were final.

Results:
Physicians (n=227) provided data on 617 patients with DS (Europe n=347; USA n=99; Asia n=171). Mean (SD) patient age was 9.7 (8.4) y and median age at onset was 1.0 y. Patients were receiving a mean (SD) of 2.1 (1.2; range 1–12) treatment regimens. The 3 most prescribed current treatments were valproate (55%), clobazam (33%) and stiripentol (26%); 40% (n=249) were receiving ODSI DS medications (26% stiripentol; 13% cannabidiol; 6% fenfluramine). Of patients who received > 1 treatment regimen (n=401), 74% had a new treatment added and 43% switched treatment. The most common reasons for discontinuation overall included lack of efficacy (68%, 91/134), reduced efficacy with continued use (49%; 65), and AEs (28%, 37). Similar discontinuation reasons were reported for DS ODSIs. Over half of the patients (55%) experienced ≥ 1 AE on their current regimen (mean, range of AEs in those experiencing ≥ 1: 2.5, 1–11), with the most reported AE being somnolence (25%); 52% of those receiving DS ODSI had ≥ 1 AE and 24% experienced somnolence. AEs had at least some impact on QoL for 81% of patients (274/338) and a moderate to severe impact for a quarter (25%). Only a third (28%–34%) had well controlled seizures for the most common seizure types (see tables). Overall, 71% had received rescue medication (74% receiving DS ODSI) with diazepam being the most frequently prescribed (32% overall; 35% for the DS ODSI subgroup). Additional data are shown in the tables.

Conclusions:
Patients with DS have a large treatment burden characterized by a high rate of AEs that impact QoL, high frequency of rescue medication use, and low rates of well controlled seizures resulting in frequent treatment switches and polypharmacy despite the availability of DS ODSI medications. There is a need for new treatment options with a balanced risk benefit profile that can be combined with current ASM with low or no drug-drug interactions.

Funding:
Analysis funded by Takeda Pharmaceutical Company Ltd.