(57) Tuberous sclerosis complex–associated neuropsychiatric disorders (TAND) outcomes following adjunctive cannabidiol (CBD) treatment: 3-month analysis of the open-label phase 3b/4 trial EpiCom

Background: : Limited treatment options exist for tuberous sclerosis complex (TSC)-associated neuropsychiatric disorders (TAND), which affect ≈90% of people with TSC. A plant-derived, highly purified pharmaceutical formulation of cannabidiol (CBD; Epidiolex®) is approved for the treatment of seizures associated with TSC; anecdotal evidence suggests neuropsychiatric improvements. EpiCom (NCT05864846) is evaluating behavioral and other outcomes after adjunctive CBD treatment in participants with TSC-associated seizures.

Objective: : To report the prespecified 3-month intermediate analysis of EpiCom.

Methods: : In this open-label study, participants received CBD (100 mg/mL oral solution) ≤25 mg/kg/day and standard of care (SOC) for 26 weeks; followed by CBD with SOC/SOC alone for up to 52 weeks overall. Most problematic behavior (MPB) on the TAND Self-Report Quantified Checklist (TAND-SQ) and Aberrant Behavior Checklist (ABC) were assessed at Week 13; and Caregiver Global Impression of Severity (CareGI-S) and Clinician Global Impression of Severity (CGI-S) scales were assessed at Weeks 4 and 13.

Results: : In this analysis, 24 participants were enrolled, 19 started CBD, and 4 discontinued. In participants with ≥1 postbaseline assessment (n=17), median (range) age was 21 (5–42) years. At baseline, 8 participants had seizures (47%), with a mean (SD) of 4 (7) seizures per 28 days. The median (range) number of antiseizure medications (ASMs) at baseline was 3 (1–5). The most common concomitant ASMs used were topiramate (35%), everolimus (29%), and lamotrigine (29%). At baseline, the mean (SD) MPB numerical rating scale (NRS) value was 8.8 (1.01), suggesting severe TAND problems; most common manifestations were mood swings (24%) and aggressive outbursts (18%). At Week 13 (n=5), mean (95% CI) change from baseline in MPB NRS was −4.6 (−8.1, −1.1). Of 7 TAND-SQ clusters, the greatest changes were in dysregulated behavior and overactive/impulsive scores. In the ABC, the greatest changes were in irritability and hyperactive noncompliance. Compared with baseline, at Weeks 4 and 13, a smaller proportion of caregivers and clinicians rated behavioral problems as severe/very severe on CareGI-S and CGI-S. Adverse events occurred in 12/19 participants (63%); most common were diarrhea (42%), vomiting, decreased appetite, and lethargy (11% each).

Conclusions: : In this intermediate analysis, reductions were observed on TAND-SQ and ABC subscales and in the severity of behavioral problems reported by caregivers and clinicians following CBD initiation. The safety profile was consistent with prior studies.

Sponsorship:: Jazz Pharmaceuticals, Inc.