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Abstracts

Long-Term Effectiveness of Cannabidiol (CBD) Against Focal Seizures in Tuberous Sclerosis Complex (TSC): Results from the GWPCARE6 Open-Label Extension (OLE) Trial

Abstract number : 2.498
Submission category : 7. Anti-seizure Medications / 7B. Clinical Trials
Year : 2023
Submission ID : 1387
Source : www.aesnet.org
Presentation date : 12/3/2023 12:00:00 AM
Published date :

Authors :
Presenting Author: Joyce Y. Wu, MD – Ann & Robert H Lurie Children’s Hospital of Chicago, Northwestern University Feinberg School of Medicine

E. Martina Bebin, MD, MPA – University of Alabama School of Medicine; Teresa Greco, PhD – Jazz Pharmaceuticals, Inc., Gentium Spa; Kelly Simontacchi, PhD – Jazz Pharmaceuticals, Inc.

Rationale: Add-on CBD reduced TSC-associated seizures (focal and generalized) in the randomized controlled trial (RCT) GWPCARE6 (NCT02544763) and its OLE (NCT02544750). This post hoc analysis evaluated the effectiveness of CBD specifically against focal seizure subtypes in the OLE.

Methods: Patients received plant-derived highly purified CBD (Epidiolex®; 100 mg/mL oral solution) at 25 or 50 mg/kg/d or placebo in the RCT, which included a four week titration and twelve week maintenance period. In the OLE trial, all patients received CBD (maximum dose up to 50 mg/kg/d). Patients could receive treatment for up to one year, except in the United States and Poland, where they could continue treatment beyond one year. In this post hoc analysis, the effectiveness of CBD was evaluated as the percentage change from baseline in the 28-day monthly average and responder rates (RRs; ≥50%, ≥75%, and 100% reduction) of focal seizure frequency across twelve week intervals through 144 weeks of treatment. Safety results are reported for the full OLE treatment period.

Results: Of 224 randomized patients in GWPCARE6, 199 (89%) entered the OLE; of these,168 (84%) reported focal seizures, and 89 (45%) reported generalized seizures. In the focal seizure cohort, the median age was 10.2 years (range, 1–56 years), and patients were taking a median of 4 (range, 0–15) concomitant antiseizure medications (ASMs). The most commonly used ASMs included valproate (40%), vigabatrin (35%), levetiracetam (27%), clobazam (25%), and lamotrigine (22%). The median duration of exposure to CBD was 596 days (range, 18–1462 days), and the median modal dose was 25 mg/kg/d (range, 5–50 mg/kg/d). CBD treatment was associated with a median reduction of 54–88% in overall focal seizures across 12-week intervals through 144 weeks. With respect to seizure subtypes, there was a median reduction of 56–84% in focal aware seizures (FAS), 54–92% in focal impaired awareness seizures (FIAS), and 52–74% in focal to bilateral tonic-clonic seizures (FBTCS) with CBD treatment through 144 weeks (Fig. 1). RRs for overall focal seizures throughout the OLE were 54% for ≥50% reduction, 33% for ≥75% reduction, and 2% for 100% reduction. RRs for focal seizure subtypes were consistent with the overall focal seizure RRs (Fig. 2). Treatment-emergent adverse events (TEAEs) were reported by 96% of patients at any time during the OLE. Most frequently reported TEAEs ( >20% of all patients) were diarrhea, seizures, pyrexia, decreased appetite, and vomiting.

Conclusions: These findings highlight a robust and sustained effect of CBD across all focal seizure subtypes in patients with TSC. The safety profile was consistent with that observed in the overall CBD clinical development program. These findings further support the real-world clinical utility of CBD across focal seizure subtypes in TSC.

Funding: Jazz Pharmaceuticals, Inc.

Anti-seizure Medications