Transdermal CBD Efficacious in Children With Developmental and Epileptic Encephalopathies

Ingrid Scheffer, MBBS, PhD, FRACP, FAES, FAHMS, FAA, FRS

Results from the BELIEVE (ZYN2-CL-025) open-label clinical trial presented at the American Epilepsy Society (AES) Annual Meeting, December 4–8, 2020, show that ZYN002 cannabidiol (CBD; Zynerba Pharmaceuticals) transdermal gel was well tolerated and reduced seizure frequency in adolescents and children with developmental and epileptic encephalopathies (DEE) such as West syndrome, Lennox-Gastaut syndrome (LGS), and Dravet syndrome (DS).¹

These results were presented by Ingrid Scheffer, MBBS, PhD, FRACP, FAES, FAHMS, FAA, FRS, laureate professor, and chair, Pediatric Neurology, The University of Melbourne; Honorary Senior Research Fellow, The Florey Institute of Neuroscience and Mental Health; Honorary Research Fellow, Murdoch Children's Research Institute; Director of Pediatrics, Austin Health, who said that “BELIEVE is the first clinical trial of ZYN002 (transdermal CBD) in DEEs. These data suggest meaningful reductions in focal impaired awareness seizures (FIAS) and tonic-clonic seizures (TCS) with ZYN002 treatment which is maintained through to 12 months.”

Scheffer and colleagues enrolled 48 patients in the study, all of which were analyzed for safety and 46 of which were analyzed for efficacy. The mean age of the patients was 10 years (range, 3–16). Weight-based doses of ZYN002 in 125 mg or 250 mg were applied every 12 hours during a 26‐week treatment period following a 4-week baseline period. Doses could be titrated up to a dose of 375 mg (<25 kg) or 500 mg (>25kg) twice daily.

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In 33 patients with focal impaired awareness seizures and/or tonic-clonic seizures at baseline, there was up to 58% median monthly reduction in these seizure types from Week 8 to Week 26 and up to 63% of these patients experienced a ≥50% reduction in monthly seizure frequency during this time period.

At least 1 treatment-related adverse event (TEAE) occurred over 26 weeks in 29 (60.4%) patients, of which 93% were mild or moderate. The most frequent TEAEs were application site dryness, application site pain, and somnolence, each with an 8.3% occurrence rate. Patients with a new onset drug-related adverse event decreased from 38% at Week 4 to 3% at Week 26.

“ZYN002 was well tolerated over 18 months of treatment in a medically fragile patient population of children and adolescents with DEEs. The positive benefit/risk profile of ZYN002 in this trial supports further study in patients with DEEs and FIAs and TCS,” Scheffer and colleagues concluded.

Zynerba’s transdermal patch is not the first investigation of CBD’s potential in the epilepsy space, of course, as GW Pharmaceuticals’ product, marketed as Epidiolex, was granted approval in June 2018, and gained a new indication for tuberous sclerosis complex in 2020. New data on that agent were also presented at AES 2020, by Batool Hussain, MBBS, neurology resident physician, University of California, Irvine, were results from a retrospective review of electronic medical records of patients with drug-resistant epilepsy treated at the comprehensive epilepsy program at the University of California, Irvine Medical Center that confirmed the effectiveness of CBD (Epidiolex).²

In all 3 patient groups assessed (n = 33), which included those with focal epilepsy (n = 12), LGS (n = 19), and primary generalized epilepsy (n = 2), there was a 58.2% mean reduction in seizure frequency (P = .002).

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REFERENCES

1. Scheffer I, Hulihan J, Messenheimer J, et al. ZYN002 cannabidiol transdermal gel in children and adolescents with developmental and epileptic encephalopathies: An open-label clinical trial (BELIEVE (ZYN2-CL-25)). Presented at AES 2020 Virtual Meeting; December 4–8, 2020. Abstract 983.
2. Husssain B, Lin JJ, Mnatsakayan L, Gupta IS, Lu X, Sazgar M. The Effectiveness of Cannabidiol as Treatment for Drug Resistant Epilepsy: A Retrospective Analysis. Presented at AES 2020 Virtual Meeting; December 4–8, 2020. Abstract 978.