Cannabidiol Treatment for Tuberous Sclerosis Complex

Elizabeth Thiele, MD, PhD: One of the presentations I was most excited about at AAN [American Academy of Neurology] was the open-label extension from the GW [Pharmaceuticals, plc] trial in tuberous sclerosis complex [TSC]. Taking care of patients with tuberous sclerosis has been a focus of the majority of my career. We know that two-thirds of patients with tuberous sclerosis develop highly refractory epilepsy. This is much higher than what is seen in the general epilepsy population.

What we saw in the randomized controlled portion of the trial is that similar to LGS [Lennox-Gastaut syndrome] and Dravet syndrome, CBD [cannabidiol] appears to be effective for many people with refractory seizures in TSC. What we learned from the open-label extension, similar to the LGS and Dravet trials, is that the efficacy is maintained and the tolerability is good.

The difference between the TSC trial and the LGS and Dravet trials is that the doses of CBD were higher. As opposed to 10 and 20 mg/kg per day, it was 25 and 50 mg/kg per day.

We also learned from the randomized controlled portion that efficacy is there. It’s not really linear. The efficacy at 50 mg/kg is pretty similar to what we saw in the other trials, but the higher concentration, or a higher dose, is also pretty well tolerated.

As expected, there were more adverse events. Particularly, there were more cases of diarrhea and more fatigue. It’s important to know that if patients do need to titrate up to those higher doses, it can still be safe, well tolerated, and effective.

Another abstract at AAN that involved the GW CBD trials was an abstract about a tuberous sclerosis CBD trial. That was a really interesting abstract looking at how soon efficacy was seen in those patients. When we start a patient on a medication, it’s important to know if it will take weeks to titrate up to a certain level before we see efficacy. Or can it be seen earlier?

Another reason to look at this is, since the trial did include higher doses, was to see, once we saw how soon efficacy occurred, if those patients would also possibly respond at a lower dose, as we saw in the LGS and the Dravet syndrome trials. Efficacy was seen pretty early. Typically, efficacy was seen within the first 2 weeks of the trial. During the titration, people were working up to their dose, so that was also good. We also learned from that data analysis that the adverse events were seen relatively early, and many resolved within the course of treatment. Again, this tells us that if we do start patients on GW CBD, we can let the families know that they won’t have to wait months to see efficacy from this drug, which matters. If you’re watching your child have seizures or if you’re having seizures daily, it’s good to know it won’t take months, hopefully, for a medication to work. It may be a matter of weeks. Also, if we are going to have tolerability issues, we will see them early on. We’re learning how to troubleshoot those to make sure our patients tolerate this medication well.