(137) Long-term Efficacy and Safety of Cannabidiol (CBD) in Patients with Tuberous Sclerosis Complex (TSC): 4-year Results from the Expanded Access Program (EAP)

Rationale: The EAP, initiated in 2014, provided open-label CBD to patients with treatment-resistant epilepsies at 25 U.S. epilepsy centers. Prior publications reported results through December 2016, with one reporting on 18 patients with TSC through August 2015 (Hess et al, 2016). Results of 34 patients with TSC through January 2019 are presented here; the objective was to evaluate the long-term efficacy (up to 192 weeks) and safety (up to 233 weeks) of add-on CBD in the cohort of patients with TSC in the EAP final analysis.

Methods: Patients received plant-derived highly purified CBD (Epidiolex^®; 100 mg/mL oral solution) increasing from 2–10 mg/kg/d to tolerance or maximum 25–50 mg/kg/d dose, depending on the study site. Efficacy endpoints were the percentage change from baseline in convulsive, focal, and total seizures and responder rates across visit windows (12-week windows through 192 weeks). Safety endpoints were measured by adverse events (AEs).

Results: Of 892 patients in the safety analysis set, 34 patients had a diagnosis of TSC. Of those with TSC, 8 (24%) patients withdrew; due to lack of efficacy (4 [12%]), AE of diarrhea (1 [3%]), and other reasons (3 [9%]). Patients were a mean (range) age of 12.4 (1.8–31.2) years and were taking a median (range) of 3 (1–7) concomitant antiepileptic drugs (AEDs) at baseline; the most common baseline AEDs were clobazam (20 [59%]), lamotrigine (14 [41%]), levetiracetam (11 [32%]), and valproate (6 [18%]). The median (Q1, Q3) top CBD dose was 40 (25, 50) mg/kg/day. The median (Q1, Q3) duration of exposure to CBD was 1102 (414, 1341) days. Baseline median (Q1, Q3) monthly seizure frequency for the efficacy analysis set was 46 (18, 76) for convulsive, 37 (24, 84) for focal, and 64 (31, 148) for total seizures. Median percent reduction in seizure frequency during the first 48 weeks ranged from 48–55% for convulsive, 61–75% for focal, and 44–56% for total seizures; and the overall pattern of response was maintained through 192 weeks, with some variation between visit windows due to the decreasing sample size. Similarly, convulsive, total, and focal seizure responder rates (≥50%) were maintained through 192 weeks (Figure 1). AEs occurring at any time up to 233 weeks were reported by 94% of patients and serious AEs by 47%; there were no deaths. Most common AEs were somnolence (32%), diarrhea (29%), convulsion (18%), and vomiting (18%) (Table 1). Liver-related AEs occurred in 1 patient (3%) who had an abnormal liver function test.

Conclusions: CBD treatment in patients with TSC was generally well tolerated and the AE profile was similar to that reported in the overall interim EAP analysis (Szaflarski et al, 2018) and the randomized controlled trial (Thiele et al, 2019). Add-on CBD resulted in sustained seizure reduction in patients with TSC for up to 192 weeks with an acceptable safety profile.

References:
Hess EJ et al. Epilepsia. 2016; 57(10): 1617-1624.
Szaflarski JP et al. Epilepsia. 2018; 59(8): 1540-1548.
Thiele E et al. AES Abstract. 2019; https://www.aesnet.org/meetings_events/annual_meeting_abstracts/view/2421288

Funding: Please list any funding that was received in support of this abstract.: GW Research Ltd