AAN 2026: How Identifying Genetic DEEs Within Existing Trial Data Could Expand the Role of Cannabidiol in Epilepsy Treatment

In an interview with Pharmacy Times at the 2026 American Academy of Neurology (AAN) Annual Meeting, Elizabeth Thiele, MD, PhD, director of pediatric epilepsy and director of the Herscot Center for TSC at Massachusetts General Hospital, explained that Lennox-Gastaut syndrome is not a single-etiology condition but rather a diagnosis encompassing many underlying genetic causes, making existing LGS trials basket trials that likely enrolled a substantial number of patients with developmental and epileptic encephalopathies (DEEs).

Pharmacy Times: Can you introduce yourself and explain your current role?

Elizabeth Thiele, MD, PhD: Hi. My name is Elizabeth Thiele, and I'm director of pediatric epilepsy at Massachusetts General Hospital and also director of the Herscot Center for TSC, also at Mass General.

Pharmacy Times: Can you give us a brief overview of this subgroup analysis—what you were looking at and why this patient population was worth examining separately?

Thiele: As you know, GW and Jazz conducted two pivotal clinical trials in Lennox-Gastaut syndrome (LGS), both of which were positive and led to the FDA approval of Epidiolex for the treatment of LGS. Since those trials, the whole concept of DEEs—developmental and epileptic encephalopathies—has become much more prominent in the field, and we now have over 1,000 genes known to be associated with epilepsy. In a way, every LGS trial has been a basket trial of sorts, because LGS is not a single etiology—many different underlying causes can lead a patient to develop Lennox-Gastaut syndrome. We thought it would be worthwhile to go back and ask: of the patients enrolled in the LGS trials, how many actually had a confirmed DEE? We expected many would, because a substantial number of children who develop LGS have an underlying genetic etiology. Since we know cannabidiol can be effective in LGS, the question became whether we could demonstrate that many of those LGS trial patients were also, in fact, DEE patients.

Pharmacy Times: You identified 53 participants with a confirmed genetic DEE on top of their LGS diagnosis—how straightforward was it to identify those patients within the existing trial data?

Thiele: To identify patients with a genetic etiology, we had to go back through all the patients enrolled in the trial, because part of the enrollment process involved documenting whether the cause of their LGS was known and whether they had undergone genetic testing. Some patients had genetic testing performed as part of the trial itself. When a genetic mutation was identified, the next step was determining whether that mutation was a known pathogenic variant and whether it met criteria for a DEE. It was a somewhat tedious process, but I think it was well worth doing.

Pharmacy Times: Controlled data in genetic DEEs are described as limited—what does this analysis add for clinicians who are treating patients with an underlying genetic etiology driving their LGS?

Thiele: It is true that controlled trial data for DEEs is limited, though we are seeing growth with the Dravet syndrome trials, the tuberous sclerosis complex trials, and the CDKL5 deficiency disorder trials, and I think that is a trend many pharmaceutical companies are pursuing. The value of this analysis is in demonstrating that in LGS trials—not just the cannabidiol trials, but other LGS trials as well—there were very likely many patients who had underlying DEEs. This suggests that medications like cannabidiol are going to have broader efficacy and, hopefully, broader clinical utilization. There is also increasing focus in clinical practice on determining whether a patient has an underlying DEE, which makes this kind of data all the more relevant.

Pharmacy Times: For pharmacists, what are the key safety takeaways from this subgroup, and does the profile look meaningfully different from what's been established in the overall LGS population?

Thiele: That is a very good question, because whenever you examine a subgroup analysis, you wonder whether the tolerability and safety profile differs, not just the efficacy. We were very pleased to find that the tolerability and safety profiles in the genetic DEE subgroup were the same as in the overall trial population. Epidiolex has shown an extremely consistent safety and tolerability profile from the early expanded access program through the pivotal trials in Dravet syndrome, LGS, and tuberous sclerosis complex and in broad clinical use. Adverse events were observed in both the placebo and treatment groups, with the most common being diarrhea and upper respiratory infection. For pharmacists, the key takeaway is that cannabidiol continues to have a very favorable safety profile, and its drug-drug interactions are now well characterized—most notably with clobazam. Using it safely is not overly challenging, and this subgroup analysis reinforces confidence in its use across patients with genetic DEEs.