Authors :
Presenting Author: Elizabeth A. Thiele, MD, PhD – Massachusetts General Hospital, Boston, MA, USA
John A. Lawson, PhD – Sydney Children’s Hospital, Randwick, Australia; Katarzyna Kotulska, MD – The Children's Memorial Health Institute, Warsaw, Poland and ERN EpiCare: A European Reference Network for Rare or Low Prevalence Complex Diseases, Bron, France; Farhad Sahebkar, MD – Jazz Pharmaceuticals, Inc, Carlsbad, CA, USA; Teresa Greco, MD, PhD – Jazz Pharmaceuticals, Inc, Gentium Srl, Villa Guardia, Italy; Timothy B. Saurer, PhD – Jazz Pharmaceuticals, Inc, Carlsbad, CA, USA
Rationale:
Add-on CBD reduced TSC-associated seizures in the randomized controlled trial (RCT) GWPCARE6 (NCT02544763) and its OLE (NCT02544750). This post hoc analysis evaluated the efficacy and safety of CBD in pediatric (<18 y) and adult (≥18 y) patients of GWPCARE6.
Methods:
Patients received CBD (Epidiolex®; 100 mg/mL oral solution) at 25 mg/kg/d (CBD25) or 50 mg/kg/d (CBD50) or placebo in the RCT, which included a 4-week titration and 12-week maintenance period. In the OLE, all patients received CBD (maximum dose up to 50 mg/kg/d). TSC-associated seizure responder rates with ≥50% and ≥75% reductions from baseline are reported for the RCT maintenance period and the OLE for pediatric and adult patients. Adverse events (AEs) are reported for the full RCT and OLE phases.
Results:
Of the 224 patients treated in the RCT, 166 patients (74%) (CBD25, n=55; CBD50, n=55, placebo, n=56) were pediatric and 58 (26%) (CBD25, n=20; CBD50, n=18; placebo, n=20) were adult. The median (range) age was eight yo (1–18) in the pediatric subgroup and 25 yo (18–57) in the adult subgroup. At RCT baseline, the pediatric and adult patients were taking a median (range) 3 (1–5) and 3 (0–5) antiseizure medications, respectively, and had a median (interquartile range) 62 (29–125) and 49 (28–72) TSC-associated seizures/28 days, respectively. After the RCT completion, 153 (92%) pediatric and 46 (79%) adult patients continued to OLE (median treatment duration, 680 and 383 days, respectively). During the RCT maintenance period, 47% of pediatric patients taking CBD25, 52% taking CBD50, and 21% taking placebo had ≥ 50% reduction in seizure frequency; ≥ 50% responder rates in adult patients were 50% for CBD25, 50% for CBD50, and 25% for placebo (Table 1). A ≥ 75% reduction in TSC-associated seizures was observed in 24% of pediatric patients taking CBD25, 28% taking CBD50, and 5% taking placebo; in adult patients, 20% taking CBD25, 31% taking CBD50, and 5% taking placebo had ≥ 75% reduction. During the OLE, ≥ 50% responder rate was observed in 53% of pediatric patients and 54% of adult patients. A ≥ 75% reduction in TSC-associated seizures was observed in 33% of pediatric patients and 33% of adult patients. During the RCT, AEs were reported in 96%, 100%, and 95% of pediatric patients and 85%, 100%, and 95% of adult patients taking CBD25, CBD50, and placebo, respectively. During the OLE, AEs were reported in 97% of pediatric patients and 91% of adult patients (Table 2).
Conclusions:
The efficacy of CBD was similar for adult and pediatric patients during the RCT. Response rates observed in both age subgroups were durable and maintained throughout the OLE. Safety profile was similar for pediatric and adult subgroups during the RCT and OLE and was consistent with the overall population. These results support long-term use of CBD for seizures associated with TSC in both pediatric and adult patients.Funding:
Jazz Pharmaceuticals, Inc.