Elaine C. Wirrell, MD: The data from my practice are very similar to what was presented in the clinical trials. Overall, in both of those conditions, about 40% of children will have a significant reduction in seizures, and a smaller proportion had an even more significant reduction in seizures. I don’t have anybody who has become completely seizure-free on those medications, but again, for the developmental and epileptic encephalopathies like Dravet and Lennox-Gastaut, seizure freedom is generally not really an achievable goal. But there is a reduction in seizures, and particularly the drop seizures for LGS [Lennox-Gastaut syndrome], which leads to an improved quality of life. Similar to what has been shown in the clinical trials, oftentimes you do get a bit of nausea and a bit of loose stools. What I’ve learned in my practice is, I start the children with my initial target, going for 10 mg/kg. Many of the children will respond with that. It’s better tolerated, and then you can always push up more slowly if you haven’t quite gotten the effect that you want, but it is well tolerated. I initially shoot for 10 mg/kg, and then I will go up as high as 20 mg/kg if we need to do that.

Elizabeth Thiele, MD, PhD: Having used this medication now for 8 years—because with the expanded access program we started our patients in 2014—I have continued to be impressed with the safety and tolerability. It’s one of our better-tolerated medications, and I have been impressed with the efficacy. I agree, the important message I thought for the patient community initially was this is not the silver bullet for epilepsy. Because with all the marketing around CBD and that CBD can fix everything, there was a great hope that this would be it, and it’s not. But we have had many patients who have benefited, and I do have some children, including ones who were in the expanded access program, who have been seizure-free now since starting the medication. It’s not a silver bullet, but clearly a lot of people are benefiting from it.

Also, shown from the open-label extension data from both the LGS trials and the Dravet trials, we know in personal experience, and from the trial data that this can be well tolerated long term, and the efficacy maintains. Early on there were a lot of haters, is what I say, who opposed the idea of using cannabidiol as treating seizures, then thinking it only worked because it potentiated clobazam, and then its efficacy waned. I don’t think that’s true. For some of our patients, like many of our other treatments, the efficacy may appear to wane with time and who knows if that’s the efficacy waning or just the child’s epilepsy trajectory? The other thing I thought was really interesting in the approval of cannabidiol, unlike our other medications, all these medications in trials are add-on therapy to the patient’s existing. Usually, the FDA labeling is adjunctive therapy in the refractory setting, and the FDA labeling for cannabidiol didn’t contain either of those words. Neither adjunctive nor refractory. Have you considered or do you have the experience yet of using it in the first line for any patients, or not yet?

Elaine C. Wirrell, MD: I have not used it in the first line for any patients yet, but I am using it earlier, particularly in Lennox-Gastaut. It’s as effective as many of our other medications. In many cases, it’s better tolerated than the other medications, so I do use it early, but I haven’t used it first line yet. Do you have experience in that?

Elizabeth Thiele, MD, PhD: I’ve been tempted, especially in the Dravet population. You come in, you can say, “Aha, this is Dravet.” We have used a ketogenic diet very early. After a first seizure, if a gene panel shows SCN1A, we’ve started children on the ketogenic diet. I don’t think right now the payers would be willing to reimburse it as a first-line medication yet. Even though we’re getting it approved pretty easily, and we’re getting approved off-label pretty easily, we still get some pushback if children haven’t been on particular medications. When it first was approved, one of the payers wanted the child to have tried felbamate before approving CBD, which I thought was ridiculous.

Elaine C. Wirrell, MD: Wow.

Elizabeth Thiele, MD, PhD: What’s it like in your part of the world with regard to having it approved? Is there a difficulty with that, or not really?

Elaine C. Wirrell, MD: I haven’t had big difficulty for the FDA-approved indications. When I’m using it off label, that can be a little bit more challenging. But for the indications, that’s been pretty good. The other thing though, just a couple of other comments on CBD. First, it’s approved for age 1 year and older. That’s different than the other medication that we’re going to be talking about, fenfluramine, which is for 2 years and older. You do have the ability to have an indication that’s approved at a younger age.The other thing for CBD, as a clinician myself, and for many of my families, I’m very happy to have a reputable pharmaceutical-grade product that you could feel very safe about giving to a child. When we talk about CBD, it’s also important to say that all of the results from those clinical trials were based on a pharmaceutical-grade product.

Elizabeth Thiele, MD, PhD: That’s a good point. That’s a conversation all of us have had for now years with our patients. It’s an interesting experience. Eight years ago, people were coming in teaching me about CBD, because what did I know about cannabis, CBD, THC [tetrahydrocannabinol], cannabinoids? It’s a very important point. I agree, particularly before the FDA approval and its availability, many of my patients wanted to try CBD. We had patients flying to Colorado, we had patients growing their own, we had patients getting it from dispensaries, and the conversation over and over again that, “I don’t know what your child is getting. Not only do I not know what the CBD concentration is, I don’t know what other cannabis compounds or hemp compounds, I don’t know if there are pesticides or heavy metals.” We all practice responsibly and knowing that every time one of my patients gets a dose of Epidiolex, I know exactly what they’re getting, and it’s the same thing. Thank you for bringing that up because that’s a really good point. Yes, it was the tuberous sclerosis trial that extended the FDA approval down to 1 year of age, which you’re right, it can make a difference, particularly since we’re diagnosing Dravet syndrome before the age of 2, oftentimes. Awesome. Anything else on CBD before we head to the other new big kid?

Elaine C. Wirrell, MD: No. Just to say, it probably has a broader spectrum than what it is approved for. When you look at how it works, the numbers are similar in tuberous sclerosis, LGS, and Dravet. That tells me that this is a probably a broader spectrum agent that likely has utility beyond just those 3 conditions.

Elizabeth Thiele, MD, PhD: I agree. As long as I’ve been doing this, I’ve always said if something can work in LGS, it probably can work in anything because it’s so difficult to treat them.

This transcript has been edited for clarity.