Epidiolex CBD Treatment Effective Across Range of Developmental Epileptic Encephalopathies

A recently presented post-hoc analysis of several phase 3 randomized controlled trials (RCTs) showed that cannabidiol (CBD) treatment with Epidiolex (Jazz Pharmaceuticals), an FDA-approved product, is effective in reducing seizures and total seizure frequency in patients with developmental epileptic encephalopathies (DEEs). Notably, the analysis excluded more known DEEs like Dravet syndrome (DS), Lennox-Gastaut syndrome (LGS), and tuberous sclerosis complex (TSC), further supporting Epidiolex’s effectiveness across a broad range of DEEs.¹

Presented at the 2025 American Epilepsy Society (AES) Annual Meeting, held December 5-9 in Atlanta, Georgia, the analysis featured 135 patients with a DEE, genetic epilepsy, or rare epilepsy syndrome from an expanded access program (EAP). Excluding those with DS, LGS, and TSC, the cohort included patients with Aicardi syndrome (12.6%), CDKL5 mutations (14.8%), epilepsy with myoclonic-atonic seizures (8.1%), Dup15q syndrome (8.1%), early infantile epileptic encephalopathy (4.4%), febrile infection–related epilepsy syndrome (9.6%), myoclonic absence epilepsy (3.7%), SCN2A mutations (3.7%), Sturge-Weber syndrome (3.7%), and other genetic epilepsies (31.1%).

Led by Elizabeth Thiele, MD, PhD, director of the Pediatric Epilepsy Program at Massachusetts General Hospital, CBD treatment was associated with a median reduction of 58.1% and 51.8% in convulsive and total seizures, respectively, after 12 weeks compared with an external placebo control arm (ECA). Notably, these results were maintained through week 48, with reductions of 63.5% and 60.0%. Among patients with at least a 50% reduction in convulsive and total seizures, investigators recorded mean estimates of 57.4% and 54.3%, respectively, at week 48.

Coming into the study, patients were mostly on clobazam (40%) and levetiracetam (33%). In comparative analyses, patients on CBD demonstrated a 43% greater reduction in seizures vs those on ECA (P <.001). Furthermore, physician-reported Global Impression of Change (GIC) was 72.2% and 82.1%, respectively, at week 12 and 48. In addition, caregiver-reported GIC improvement was 73.7% and 82.0%, at those respective time points.

CBD was first greenlit in June 2018 for the treatment of DS and LGS, marking the first FDA-approved medication derived from cannabis and the first specific approval for DS. Years later, in 2020, the FDA expanded the drug’s label to include the treatment of TSC, using data from the phase 3 GWPCARE6 trial (NCT02544763) as the basis for the expansion.

In the analysis, safety was reported for the entire treatment period. Overall, treatment-related adverse events (TEAEs) occurred in 51.9% of patients, with diarrhea (18.6%), fatigue (12.8%), and somnolence (12.2%) as the most common. In their conclusions, the study authors wrote that these findings suggest that CBD may be an effective ASM for a broad range of DEEs and other rare epilepsies, although further investigation is warranted.

READ MORE: AES Poster Lays Insights Into EEG and MRI Biomarkers of MOGAD-Related Epilepsy

An additional study on Epidiolex, presented at AES 2025, focused on the real-world, long-term use of the drug, and compared treatment responses within and outside its FDA approved indications. In this preliminary analysis, which included 50 patients, most of which had focal epilepsy (84%), retention rates were 90% at 3 months, 80% at 6 months, and 63.3% at 12 months, 60.4% at 24 months, and 56.3% at 36 months. Overall, 18.75% of patients achieved seizure freedom for at least 6 months while 12.5% achieved seizure freedom for 12 months.

Approximately half of the patients (52%) had some degree of static encephalopathy, and epilepsy syndromes were present in 90%, including 74% with focal epilepsy and 10% with LGS. The median age at CBD initiation was 33.5 years, with a median treatment duration of 41.4 months. Patients had previously tried an average of 6.66 antiseizure medications and were taking 2.89 concurrently, with clobazam being the most commonly used prior therapy (70%).

In total, 52% of patients discontinued CBD, most often because of intolerability (24%) or lack of efficacy (22%). Adverse events occurred in 72% of patients, with gastrointestinal issues (30%), sedation (26%), and psychiatric symptoms (16%) being most common, while discontinuations due to these events were less frequent, including sedation (8%), gastrointestinal issues (6%), and psychiatric symptoms (6%).

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REFERENCES
1. Park Y, Greco T, Simontacchi K, et al. Effectiveness of Cannabidiol in Patients With Rare Epilepsies Compared to External Placebo Control: A Post Hoc Analysis From the Expanded Access Program. Presented at: 2025 AES Annual Meeting; December 5-9; Abstract 2.337.
2. Matias E, Pandey N, Shi C, et al. Long-Term Use of Cannabidiol (Epidiolex) in Patients with Refractory Epilepsy - The UM Experience. Presented at: 2025 AES Annual Meeting; December 5-9. Abstract 2.473.