Neurelis announced today that the U.S. Food and Drug Administration (FDA) has expanded the approval of VALTOCO (diazepam nasal spray) to include children ages 2 to 5 years old for the acute treatment of seizure clusters, also known as acute repetitive seizures, that differ from a patient's usual seizure pattern.
The approval marks a significant advancement for pediatric epilepsy care, as it provides a non-invasive alternative to the current standard treatment for young children experiencing seizure clusters, which typically requires rectal administration of medication.
"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 Dr. Jurriaan M. Peters, Director of the Localization Laboratory in the Division of Epilepsy and Clinical Neurophysiology at Boston Children's Hospital and Associate Professor in Neurology at Harvard Medical School. "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."
Clinical Evidence Supporting Expanded Approval
The FDA's decision was based on data from a phase 1/2a clinical study evaluating the safety and pharmacokinetics of VALTOCO in children aged 2 to 5 years with epilepsy and seizure clusters. The open-label, single-dose study included a 180-day safety period in which caregivers administered weight-based doses of the nasal spray as needed for immediate treatment of seizure clusters.
Of the 35 patients enrolled, 31 completed the full 180-day safety period. The mean age of participants was 3.9 years, and a total of 299 doses were administered throughout the study. While 24 patients experienced treatment-emergent adverse events (AEs) and 10 patients had serious AEs, none of the serious events were determined to be treatment-related.
Dr. Eric Segal, Director of Pediatric Epilepsy at Northeast Regional Epilepsy Group and Hackensack University Medical Center, commented, "The FDA's decision to approve VALTOCO for use in early childhood highlights the established balanced safety and efficacy profile. 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."
Addressing a Significant Unmet Need
Approximately 3.4 million people in the United States have epilepsy, including 400,000 children. While chronic epilepsy can often be controlled with regular medications, some patients remain at risk for episodes of frequent seizures or acute repetitive seizures that require immediate intervention.
VALTOCO utilizes Neurelis' proprietary INTRAVAIL absorption enhancement technology, which enables the non-invasive, enhanced intranasal delivery of diazepam. The FDA previously recognized the intranasal formulation as clinically superior to the rectal gel formulation of diazepam, granting it orphan drug exclusivity.
"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.
Safety Profile and Common Side Effects
In previous clinical studies, the most common treatment-related adverse events included nasal discomfort, headache, dysgeusia (altered taste), epistaxis (nosebleed), and somnolence (drowsiness). Only 7.9% of patients showed nasal irritation, and the investigators established that the nasal spray was generally safe and comparable to the established profile of rectal diazepam.
The expanded approval maintains the same warnings and precautions as the original indication, including potential for CNS depression, risk of suicidal behavior and ideation (common to all antiepileptic drugs), and contraindications for patients with hypersensitivity to diazepam or acute narrow-angle glaucoma.
Clinical Implications
The approval of VALTOCO for younger children represents a significant advancement in seizure management, particularly for caregivers who may struggle with administering rectal diazepam during an active seizure event. The nasal spray formulation can be administered while a child is actively seizing, potentially improving treatment outcomes and reducing the stress associated with seizure management.
Healthcare providers now have an additional option for treating seizure clusters in their youngest patients, with a delivery method that may be more acceptable to both caregivers and children. This expanded approval aligns with ongoing efforts to improve the quality of life for pediatric epilepsy patients and their families by providing more practical and dignified treatment options.
Diazepam, the active ingredient in VALTOCO, is a Schedule IV controlled substance, and healthcare providers should consider this when prescribing the medication.
