Authors :
Agnies van Eeghen, MD – Emma Center for Personalized Medicine, Emma Children’s Hospital, Amsterdam University Medical Centers; Advisium, ’s Heeren Loo
Sarah Wilson, MD – McGovern Medical School, The University of Texas Health Science Center at Houston
Stevie Roszkowski, PhD – Jazz Pharmaceuticals, Inc
Maria Dunaway-Bryant, BS – Jazz Pharmaceuticals, Inc
Kasia Wajer, MMsc – Jazz Pharmaceuticals, UK Ltd.
Teresa Greco, PhD – Jazz Pharmaceuticals, Inc.
Presenting Author: Joanne Stevens, BA – Jazz Pharmaceuticals, Inc
Lisa Moore-Ramdin, MBBS, MRCPCH, DPM, FFPM – Jazz Pharmaceuticals, UK Ltd.
Petrus de Vries, PhD – Centre for Autism Research in Africa, University of Cape Town
Rationale:
Tuberous sclerosis complex (TSC)–associated neuropsychiatric disorders (TAND) can affect and reduce quality of life in almost all people with TSC, yet treatment options remain limited. A plant-derived, highly purified pharmaceutical formulation of cannabidiol (CBD; Epidiolex®) is approved for the treatment of seizures associated with TSC; anecdotal evidence also suggests some neuropsychiatric benefits. EpiCom (NCT05864846) is an ongoing phase 3b/4 study evaluating behavioral and other co-occurring outcomes after initiation of adjunctive CBD treatment in participants with TSC-associated seizures. Results from the prespecified 6-month intermediate analysis are presented here.
Methods:
In this open-label study, participants with TSC (aged 1–65 years) received CBD-OS (100 mg/mL oral solution) ≤ 25 mg/kg/day in addition to standard of care (SOC) for 26 weeks, followed by CBD with SOC or SOC alone for up to 26 additional weeks. Most problematic behavior (MPB), TAND Self-Report Quantified Checklist (TAND-SQ), Aberrant Behavior Checklist (ABC), Caregiver Global Impression of Severity (CareGI-S), and Clinician Global Impression of Severity (CGI-S) scales were assessed at baseline and Weeks 13 and 26. Data were analyzed using standard descriptive statistics.
Results:
Of 79 participants enrolled, 62 had ≥ 1 postbaseline assessment and were included for analysis. Median (range) age was 16.0 (3–42) years, and 2.0 (1–6) antiseizure medications were being used at baseline. Mean (SD) MPB numerical rating scale (NRS) value was 8.8 (1.3) out of 11 at baseline, suggesting severe TAND problems, most commonly aggressive outbursts (23%) and anxiety (11%). At Week 26 (n=23), mean (95% CI) change from baseline in overall MPB NRS was −2.3 (−3.5, −1.2). Of the seven TAND-SQ cluster severity scores, the greatest changes were seen in dysregulated behavior (−1.6 [−2.7, −0.5]) and eat/sleep scores (−1.5 [−2.7, −0.4]). Among the ABC subscales, greatest changes were seen in hyperactive noncompliance (−6.9 [−11.5, −2.3]) and irritability (−6.5 [−9.9, −3.1]) (Table). Compared with baseline, smaller proportions of caregivers and clinicians rated behavioral problems as severe or very severe at Weeks 13 and 26, respectively (CareGI-S severe: 38% vs 14% and 13%; very severe: 18% vs 4% and 13%; CGI-S severe: 47% vs 10% and 0%; very severe: 10% vs 0% and 0%; Figure). Treatment-emergent adverse events occurred in 49 participants (62.0%), most commonly diarrhea, infections, and psychiatric disorders. Of 6 serious adverse events (7.6%) reported, 4 were deemed treatment related (resolved).
Conclusions:
In this intermediate analysis, reductions were seen in the TAND-SQ and ABC subscale scores and in the severity of behavioral problems reported by caregivers and clinicians after 26 weeks of CBD initiation. The safety profile remains consistent with previous studies. These findings support the continued evaluation of effectiveness of CBD on nonseizure outcomes in patients with TSC.
Funding:
Jazz Pharmaceuticals, Inc.