Sustained seizure reductions with cannabidiol for Lennox-Gastaut syndrome

Add-on cannabidiol (CBD) in patients with Lennox-Gastaut syndrome (LGS) produced sustained seizure reductions, with no new safety concerns [1]. This was concluded from 3-year results of an open-label extension of 2 randomised controlled trials.

LGS is a rare and severe form of epileptic encephalopathy characterised by multiple seizure types, characteristic EEG findings with bursts of slow spike-wave complexes or generalised paroxysmal fast activity, and intellectual impairment. Seizures are often drug-resistant. Efficacy and safety of CBD as an add-on anticonvulsant therapy in LGS were demonstrated in two 14-week phase 3 randomised controlled trials: GWPCARE3 and GWPCARE4 [2,3]. Patients who completed either of these trials could enter the open-label extension trial GWPCARE5. Participants received plant-derived highly purified CBD (Epidiolex^® 100 mg/mL oral solution). The primary endpoint was safety.

Of 368 eligible LGS patients, 366 (99%) entered GWPCARE5. Mean age was 16 years; 33% was ≥18 years; 54% was male. At baseline, median monthly quantified seizure frequency was 80 drop seizures and 168 total seizures. During the median follow-up of 150 weeks (range 3 days to 179 weeks), one third of patients (n=119) withdrew. The incidence of adverse events (AEs) and of serious AEs was 96% and 42%, respectively; 12% of AEs led to discontinuation. Most common AEs (≥20%) included diarrhoea, convulsion, pyrexia, somnolence, vomiting, upper respiratory tract infection, and decreased appetite. Increased alanine aminotransferase occurred in 8% of patients. There were 11 deaths; none deemed treatment-related by the investigators. Efficacy outcomes over 156 weeks showed the median monthly drop seizures decreased by 48–71% and the median total seizures by 48–68%.

 

1. Patel A, et al. Abstract S25.004, AAN 2020.
2. Devinsky O, et al. N Engl J Med. 2018;378(20):1888-97.
3. Thiele EA, et al. Lancet. 2018;391(10125):1085-96.

 



Posted on 9 September, 20206 September, 2023