Cannabidiol for Lennox-Gastaut Syndrome and Dravet Syndrome

Elizabeth Thiele, MD, PhD: One of the presentations that was going to occur at the AAN [American Academy of Neurology] Annual Meeting that we were really excited about was the long-term data from the open-label extension of the GW [Pharmaceuticals, plc] CBD [cannabidiol], or Epidiolex, trial in Lennox-Gastaut syndrome [LGS]. What we found in the long-term open-label extension is that the majority of patients who participated in the randomized controlled portion did enter the open-label extension. We were really pleased to see that the tolerability, overall, was pretty good, although there were adverse effects. Most adverse effects were mild and were very similar to the adverse effects we had seen in the randomized controlled trials.

We were also very happy to see that throughout the open-label extension period efficacy was maintained, and many people had a significant reduction in seizures. At every time point, when we looked, over 6% of kids were completely seizure-free. Given the highly refractory nature of the patients who enrolled in this trial, I was really impressed by those results.

We all know that patients with Lennox-Gastaut syndrome, almost by definition, develop highly refractory epilepsy. Even though we’ve had several products available that we know can help in Lennox-Gastaut syndrome, including several that have been FDA approved for the treatment of seizures in LGS, there continues to be a significant unmet need for safe and well-tolerated therapies for these patients.

There has been a lot of enthusiasm about CBD based on the randomized controlled trials, but those were brief, several-week trials. They were 14-week trials, including titration. To see that the efficacy is maintained over a much longer period of time and that the tolerability was really pretty good means to me and a lot of other people that it looks like GW CBD is going to be a very important addition to the options we have for the treatment of these patients.

What’s also been very reassuring is that if you look across all the open-label extension trials that GW Pharmaceuticals has—the LGS open-label extension, the Dravet syndrome open-label extension, as well as the TS [tuberous sclerosis] study, we’re seeing very consistent profiles with regard to tolerability as well as maintenance of efficacy.

I think it means that although this is not a medication that’s going to be a big win for every patient, clearly, many patients are going to benefit from this.

Another presentation that was going to be presented on at AAN was the open-label extension from the GW CBD Dravet syndrome trials. Very similar to what was seen in the LGS open-label extension, the majority of patients who were in the randomized controlled trials did enter the open-label extension. Over 95% of patients from the randomized controlled trial did enter the open-label extension, and what we saw, again, which was similar to the LGS trial, is there was maintained efficacy during that time. The tolerability also continues to have a very favorable profile compared with many of our other anticonvulsant medications.

There were, which was not really surprising, a high number of adverse events. Most of them were mild, many of them resolved, and most of them did not lead to discontinuation from the trial. Again, this suggests that GW CBD is going to be a very important treatment option for patients with seizures associated with Dravet syndrome.