Authors :
Jurriaan Peters, MD, PhD – Harvard Medical School and Boston Children’s Hospital, Boston, MA; Vinay Puri, MBBS, MD – University of Louisville, Louisville, KY; Eric Segal, MD – Hackensack University Medical Center and Northeast Regional Epilepsy Group, Hackensack, NJ; Richard Gustin, PhD – Neurelis, Inc., San Diego, CA; Sunita Misra, MD, PhD – Neurelis, Inc., San Diego, CA; Adrian Rabinowicz, MD – Neurelis, Inc., San Diego, CA; Enrique Carrazana, MD – Neurelis, Inc., San Diego, CA; John A. Burns School of Medicine, University of Hawaii, Honolulu, HI
This is a Late Breaking abstractRationale: Cannabidiol (CBD) is used as an antiseizure drug (ASD) with multiple mechanisms of action that attenuate neuronal excitation. A highly purified oral solution of CBD (Epidiolex
®) is FDA-approved for treatment of seizures in patients aged ≥1 year with Dravet syndrome, Lennox-Gastaut syndrome (LGS), or tuberous sclerosis complex. In clinical studies, oral-solution CBD has enhanced the effectiveness of benzodiazepines, especially clobazam; however, concomitant clobazam is also associated with a greater number of adverse events. Diazepam nasal spray (Valtoco
®) is approved for acute treatment of seizure clusters in patients with epilepsy aged ≥6 years. This post hoc analysis from a long-term, open-label safety study (NCT02721069) examines safety and effectiveness of diazepam nasal spray in patients who also received any form of CBD treatment.
Methods: Patients (6–65 years) in the long-term, open-label safety study of diazepam nasal spray
received 5-, 10-, 15-, or 20-mg doses (based on age and weight) to treat seizure clusters; second doses could be administered 4–12 hours later if needed. Seizures and drug administration were recorded in patient diaries. Concomitant CBD use (formulation, start and stop dates, dosage, route, frequency) and treatment-emergent adverse events (TEAEs) were collected. The number of second doses given within 24 hours of the first was used as a proxy for effectiveness.
Results: Of 175 enrolled patients, 163 were treated with ≥1 dose of diazepam nasal spray. Among these patients, 119 (73.0%) did not receive CBD, while 23 (14.1%) received the FDA-approved oral-solution CBD and 21 (12.9%) received another form of CBD. On average, patients receiving oral-solution CBD were younger and more likely to have epileptic encephalopathies, including Dravet syndrome or LGS, than patients receiving another CBD preparation or no CBD (Table 1). Although rates of TEAEs and serious TEAEs were higher in patients receiving any form of CBD compared with those who did not, treatment-related TEAEs were similar among the groups (Table 2). Patients in the two CBD subgroups had similar overall TEAE rates. Rates of serious TEAEs were greater in the oral-solution CBD group; however, treatment-related TEAEs were lower in that group than those in the other CBD group. Effectiveness, measured by second dose use, was similar between no CBD (11.5%) and oral-solution CBD groups (8.2%), and higher for the other CBD group (20.3%).
Conclusions: CBD does not appear to influence the safety of diazepam nasal spray. In this cohort, patients receiving CBD are approximately twice as likely to have an epileptic encephalopathy, which may underlie the overall rates of TEAEs in this study population. Importantly, treatment-related TEAEs were generally similar across groups, with the lowest rate in those receiving oral-solution CBD. These results suggest that CBD does not alter the safety and effectiveness of diazepam nasal spray and support concomitant use in appropriate patients.
Funding: Neurelis, Inc.