Diazepam Nasal Spray Receives FDA Approval for Seizure Clusters in Individuals 2 Years and Older

The FDA has approved diazepam nasal spray (Valtoco; Neurelis Inc.) for the short-term treatment of seizure clusters, or acute repetitive seizures, among individuals aged 2 years and older. The approval follows the previously granted orphan drug designation for diazepam nasal spray with intravail (Aegis Therapeutics), a mucosal absorption enhancer technology that enables the noninvasive, enhanced intranasal delivery of diazepam.¹

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“The FDA's decision to approve VALTOCO for use in early childhood highlights the established balanced safety and efficacy profile," Eric Segal, MD, director of pediatric epilepsy at Northeast Regional Epilepsy Group and Hackensack University Medical Center, said in a news release. "VALTOCO fills a large unmet need for children with seizures and their families. I am hopeful that this product will improve quality of life for this specific population."¹

Understanding Seizure Clusters and Associated Risks

Seizure clusters involve multiple seizures occurring within hours or days, with recovery typically happening between them and the clusters ending naturally. However, individuals face a high risk of repeated clusters or status epilepticus if their seizure clusters last longer than usual, occur in closer succession, if they don’t recover well between episodes, or if rescue medications are ineffective, according to the Epilepsy Foundation.² The approval of diazepam nasal spray offers further treatment options for the nearly 3.4 million individuals in the US with epilepsy, including 400,000 children.¹

"For children who have episodes of frequent seizures, the current standard of care requiring rectal administration of medication to stop a seizure can be a significant challenge for caregivers and children alike," said Jurriaan M. Peters, MD, PhD, director, localization laboratory, division of epilepsy and clinical neurophysiology, Boston Children's Hospital, and associate professor in neurology at Harvard Medical School, in a news release. "Approval of an immediate-use intranasal diazepam treatment that can be given at any time, even while a child is actively seizing, in this young age group is an important advance for the epilepsy community."¹

Clinical Trial Data Supporting Diazepam Nasal Spray

The decision to approve diazepam nasal spray was supported by data from the phase 1/2a Stellina clinical study that evaluated a single dose of diazepam as a rescue medication in children aged 2 to 5 years who were diagnosed with epilepsy. The study aimed to assess the pharmacokinetics of diazepam after 1 intranasal dose of diazepam nasal spray, as well as analyze the long-term safety and tolerability in the 6-month open-label safety period.³

A total of 35 pediatric patients aged 2 to 5 years were included in the study, with a mean age of 3.9 years. Doses of diazepam nasal spray were based on the individuals body weight and were administered by the patient’s caregiver on an as-needed basis for immediate-use treatment for seizure clusters. A total of 299 doses were administered across 3 dosage levels: 5 mg (11 doses to 3 patients), 10 mg (238 doses to 28 patients), and 15 mg (50 doses to 4 patients). Additionally, the safety profile was evaluated on days 30, 90, and 180.⁴

The results demonstrated that among the 88.6% of individuals that completed the safety period of the study, treatment-related adverse events were reported in 20% of patients, none of which were serious.⁴ The most common reactions include somnolence, headache, and nasal discomfort.¹

The findings suggest that the safety profile of diazepam nasal spray among pediatric patients was consistent with older patients, supporting its use in this age group.⁴

"We are so grateful for all those who participated in the clinical study to enable VALTOCO to reach this milestone, especially the patients and families whose participation in the trial helped expand access to a unique immediate-use medication to help stop an episode of frequent seizures," said Craig Chambliss, Neurelis Founder and CEO.¹

REFERENCES

1. Neurelis Announces FDA Approval for Immediate Use Seizure Medication VALTOCO® (Diazepam Nasal Spray) in Ages 2 to 5. Neurelis, Inc. News release. April 16, 2025. Accessed April 16, 2025. https://www.prnewswire.com/news-releases/neurelis-announces-fda-approval-for-immediate-use-seizure-medication-valtoco-diazepam-nasal-spray-in-ages-2-to-5-302430066.html

2. Shafer P., Schachter, S., Sirven, J. Published February 4, 2022. Accessed April 16, 2025. Seizure clusters, Seizure emergencies. Epilepsy foundation. https://www.epilepsy.com/complications-risks/emergencies/seizure-clusters

3. Neurelis. Stellina. Accessed April 16, 2025. https://www.neurelisclinicaltrials.com/

4. Nair, D. R., Patel, A., Kapikian, N., Barzegar, M., Sadar, V., Coletta, B., & Shah, A. R. Safety profile of diazepam nasal spray in patients aged 2–5 years from an ongoing open-label 180-day safety period following pharmacokinetic sampling in a phase 1–2a study. American Epilepsy Society. December 2024. Accessed April 16, 2025. https://aesnet.org/abstractslisting/safety-profile-of-diazepam-nasal-spray-in-patients-aged-2-5-years-from-an-ongoing-open-label-180-day-safety-period-following-pharmacokinetic-sampling-in-a-phase-1-2a-study