Safety of Diazepam Nasal Spray in Pediatric Patients With Developmental Epileptic Encephalopathies: Results From a Long-term Phase 3 Safety Study
- PMID: 37455404
- PMCID: PMC10466939
- DOI: 10.1177/08830738231185424
Safety of Diazepam Nasal Spray in Pediatric Patients With Developmental Epileptic Encephalopathies: Results From a Long-term Phase 3 Safety Study
Abstract
Pediatric developmental epileptic encephalopathies are often refractory to treatment despite stable antiseizure therapy. The safety profile of diazepam nasal spray (Valtoco) as rescue therapy for seizure clusters was described in a long-term safety study. This post hoc analysis assessed safety and effectiveness within a subpopulation of patients with developmental epileptic encephalopathies. Of 163 treated patients, 64 were diagnosed with ≥1 pediatric developmental epileptic encephalopathy. Among the most common developmental epileptic encephalopathies were Rett syndrome (n = 16), Lennox-Gastaut syndrome (n = 9), and Dravet syndrome (n = 7). In the broad pediatric developmental epileptic encephalopathy group, 10.6% of seizure clusters were treated with a second dose, with similar proportions in the 3 individual encephalopathies. Across groups, treatment-emergent adverse event rates ranged from 66.7% to 100%. Only epistaxis (n = 2) was treatment-related and reported in >1 patient. In this long-term safety analysis in patients with developmental epileptic encephalopathies, diazepam nasal spray demonstrated a consistent safety profile, supporting its use in these hard-to-treat patients (ClinicalTrials.gov NCT02721069).
Keywords: Dravet syndrome; Lennox-Gastaut syndrome; Rett syndrome; developmental epileptic encephalopathy; diazepam.
Conflict of interest statement
The authors declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: Dr Tarquinio has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Avexis, Marinus, and Neurelis, Inc. Dr Wheless has served as an advisor or consultant for CombiMatrix; Eisai; GW Pharmaceuticals; Lundbeck; Neurelis, Inc.; NeuroPace; Supernus Pharmaceuticals; and Upsher-Smith Laboratories. Dr Wheless has served as a speaker or a member of a speakers bureau for Cyberonics; Eisai; Lundbeck; Mallinckrodt; Neurelis, Inc.; Supernus Pharmaceuticals; and Upsher-Smith Laboratories and has received grants for clinical research from Acorda Therapeutics; GW Pharmaceuticals; Insys Therapeutics; Lundbeck; Mallinckrodt; Neurelis, Inc.; NeuroPace; Upsher-Smith Laboratories; and Zogenix. Dr Segal has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Eisai, Encoded Therapeutics, Epitel, Greenwich, Lundbeck, Novartis, Nutricia, and Qbiomed and is an advisor for Neurelis, Inc. Dr Misra was an employee of and has received stock options from Neurelis, Inc. Dr Rabinowicz is an employee of and has received stock options from Neurelis, Inc. Dr Carrazana is an employee of and has received stock and stock options from Neurelis, Inc.
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