Anup Patel, MD: I think it’s wonderful that we are literally sitting on a panel with some of the people who ran these studies and published a lot of the data and have powerful journals. So I am really excited to talk about the specific studies and the data. Ian, I want you to kick it off because you were the lead in this Dravet study that helped get it to the FDA approval. Talk about what you found as far as the data and the safety profile.
Ian Miller, MD: Sure. So there have been 2 studies in LGS [Lennox-Gastaut syndrome] and 2 studies in Dravet. Only 3 of those 4 have been published so far, and the Dravet paper for which I’m the main author is still pending publication. It was actually Dr Orrin Devinsky ,MD, who got it to the FDA and led to the approval.
Thankfully, all of those efficacy readouts, number 1, were measurable statistically, right? So they were significant. And thankfully they’re all relatively consistent with one another. And out of the data that are available, the rough estimate of efficacy when you look at the primary outcomes, which I’ll talk about in one minute, is basically about a 40% reduction in seizures between pre-cannabidiol and post-cannabidiol with all the other medications kept the same. So this was an add-on therapy to whatever it is that they were taking.
Most of the individuals who were in the LGS and the Dravet study were on 2 or more medications. They were on appropriate medications, in large part clobazam and valproic acid. And the primary outcomes were drop seizures for Lennox-Gastaut and convulsive seizures for Dravet.
Anup Patel, MD: What about the LGS studies, Elizabeth? You were one of the main authors in the Lancet paper, and what did you guys see in that study? And also our other study, 1414.
Elizabeth A. Thiele MD, PhD: Yes. What I was impressed by, as Ian said, there were 2 LGS trials and 2 Dravet trials. One each where there were 2 arms: placebo and 20 mg per kg per day. The other studies for both had 3 arms: placebo, 10 mg and 20 mg per kg per day.
I was really impressed that although you have different disease populations, the efficacy in all the trials is fairly similar. So 40%, and then if you subtract the placebo response, that all of the studies for their primary and for most of the secondary endpoints met statistical significance. I thought that was pretty impressive. As we had discussed earlier, that was very similar to what we saw in an expanded access program that was published, and granted open-label, but the efficacy data there were very similar to what we saw in the RCTs [randomized controlled trials].
So I was impressed by the efficacy. I also was very impressed by the tolerability. I agree with Eric, I think if a new product comes out, it’s going to be important to know not only how effective it is, but if we can already know significant drug-drug interactions when the medication becomes available, that helps us and other physicians use the medication safely.
As you know, GW Pharmaceutical also has conducted a trial in tuberous sclerosis complex, and hopefully we’ll have those results soon. I’m also very interested to see those results because that trial used higher doses, a 25 mg and a 50 mg per kg arm, which I think will not only give us more information about efficacy, but more information about tolerability. We’ll be in a unique position that when a medication is available, we can see how effective it is over a pretty broad dose range, more than any other medications that have been in clinical trials. As well, we’ll be able to assess the tolerability, which again, since in clinical practice, all of us titrate children’s medications to where they tolerate to try to optimize efficacy, we’ll be able to safely use this medication broadly.
Anup Patel, MD: We talked about the trials and the data, but now, as Elizabeth alluded to, we’ve had children and adults on cannabidiol, or specifically Epidiolex, for several years. Elaine, can you comment on some of the long-term data that are now starting to come out as they relate to these trials?
Elaine C. Wirrell, MD: Yes. I think the exciting thing is it looks like the efficacy is maintained in many of these children. That’s really exciting. We often worry about a honeymoon effect with a lot of the medications that we’re using for Lennox-Gastaut or Dravet syndrome or intractable epilepsy. I think what we’ve seen is that the efficacy is maintained and safety-wise we’ve not seen any new signals as well. It seems to be a very well tolerated medication.
Anup Patel, MD: I think that’s going to be very important data as we move on.