Authors :
Presenting Author: Agnies Van Eeghen, MD, PhD – Emma Children's Hospital / 's Heeren Loo
Sarah M.L. Wilson, MD – McGovern Medical School, The University of Texas Health Science Center at Houston
Douglas M. Smith, MD – Minnesota Epilepsy Group
Roy E. Strowd, MD, MEd, MS – Comprehensive Cancer Center, Wake Forest School of Medicine
Jane G. Boggs, MD – Wake Forest School of Medicine
Teresa Greco, PhD – Jazz Pharmaceuticals, Inc
Joanne Stevens, n/a – Jazz Pharmaceuticals, Inc
Lisa Moore-Ramdin, n/a – Jazz Pharmaceuticals, Inc
Rationale: There are limited treatments for TAND, which affect ≈90% of people with TSC and reduce quality of life. A plant-derived, highly purified pharmaceutical formulation of
CBD (Epidiolex
®) is approved for the treatment of seizures associated with TSC; anecdotal evidence also suggests neuropsychiatric benefits.
EpiCom (NCT05864846) is an ongoing study evaluating behavioral and other outcomes after add-on CBD treatment in participants with TSC and epilepsy. Here we present the prespecified 3-month analysis of EpiCom.
Methods: Eligible participants with TSC (aged 1–65 years) who have moderate/severe behavioral challenges on the Caregiver Global Impression of Severity (CareGI-S) scale are receiving CBD (100 mg/mL oral solution) ≤ 25 mg/kg/d (based on response and tolerability) and standard of care (SOC) for 26 wks; subsequently, they may choose to continue CBD with SOC or SOC alone up to 52 wks. TAND-associated outcomes are evaluated as change from baseline in the most problematic behavior (MPB) on TAND Self-Report Quantified Checklist (TAND-SQ) and Aberrant Behavior Checklist (ABC) at wk 13 and CareGI-S and Clinician Global Impression of Severity (CGI-S) scales at wks 4 and 13.
Results: At this analysis, 24 participants had 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, 9 participants (47%) had seizures, with a mean (SD) of 4 (7) seizures per 28 days. The median (range) number of antiseizure medications at baseline was 3 (1–5). Most common concomitant medications were lamotrigine (n=6 [32%]), topiramate (n=6 [32%]), and everolimus (n=5 [26%]). Five participants completed assessments within the wk-13 visit window. 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 (n=4 [24%]) and aggressive outbursts (n=3 [18%]). At wk 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 (
Table). In ABC, the greatest changes were in irritability and hyperactive noncompliance (
Table). Compared with baseline, a smaller proportion of caregivers and clinicians rated behavioral problems as severe/very severe on CareGI-S and CGI-S at wks 4 and 13 (
Fig). Adverse events (AEs) occurred in 12/19 participants (63%); most common were diarrhea (n=8 [42%]), vomiting, decreased appetite, and lethargy (n=2 [11%] each). Four participants (21%) discontinued due to AEs (diarrhea, hypersomnia, increased transaminase, and rash).
Conclusions: In this planned intermediate 3-month analysis, improvements were seen on TAND-SQ and ABC subscales after initiating CBD. The safety profile is consistent with previous studies. Although this analysis is limited by small sample size, caregivers and clinicians reported improvements in severity of psychiatric and behavioral problems.
Funding: Jazz Pharmaceuticals, Inc.