Paediatric Neurologist University of Otago, Wellington, New Zealand
Rationale: Developmental and Epileptic Encephalopathies (DEEs) are the most severe group of epilepsies. Patients have drug-resistant epilepsy with complex comorbidities and increased mortality. Children with DEEs are medically fragile and have intellectual disability, autism spectrum disorder, and sleep disturbance. Quality of life (QoL) of children with drug-resistant epilepsy is further impacted with a larger number of antiseizure medications and increased seizure frequency underscoring a need for new therapies. We aimed to evaluate the impact of ZYN002 cannabidiol (CBD) transdermal gel on the QoL of children with DEEs and their families in an open-label study, BELIEVE (ZYN2-CL-025). Methods: This was an open‐label study of ZYN002 CBD transdermal gel in children with DEEs aged 3 to < 18 years. ZYN002 125, 250, 375, or 500 mg was applied every 12 hours for 26‐weeks. The Epilepsy and Learning Disabilities Quality of Life (ELDQOL) scale‐modified and Daily Good Day/Bad Day scores were used to quantitatively assess QOL. The Good Day/Bad Day score was a parental assessment of the child’s QOL for each day and incorporated factors such as seizure frequency, alertness, interactions, behavior and mood. A qualitative assessment of QOL was provided by caregiver response to specific questions. This was coded by two independent reviewers and categorized responses were quantified. Results: Of the 48 participants enrolled, 54.2% (26/48) were male. Mean (SD) results on the ELDQOL (N=40) showed significant improvements at Week 26 compared with baseline in seizure severity (‐0.19 [0.428], p=0.008); behavior (‐0.21 [0.384], p=0.001); and mood (‐0.15 [0.270], p=0.001). In comparing baseline to Week 26, the combined proportion of “good day” and “fantastic day” scores increased from 52.0% at baseline to 70.4%, and the combined proportion of “terrible day” and “bad day” scores decreased from 12.3% at baseline to 3.7%. Caregiver qualitative assessments (N=43) were consistent with improvements noted in the ELDQOL scale and included improvements in alertness, energy, sleep (53%); seizures (51%); cognition/concentration (47%); social or interpersonal engagement and irritability (77%); and school attendance (28%). Twenty‐nine (60.4%) participants had ≥ 1 related adverse event over 26 weeks; 93% were mild or moderate. Conclusions: Treatment with ZYN002 CBD transdermal gel may be associated with improved socio‐behavioral function and increased QoL in children and adolescents with DEEs and their families. These findings suggest a positive benefit:risk profile of ZYN002. Additional research is warranted in this difficult to treat population with DEEs. Funding: Please list any funding that was received in support of this abstract.: This research was funded by Zynerba Pharmaceuticals, Inc.