On April 16, 2025, the U.S. Food and Drug Administration (FDA) announced a significant advancement in the treatment of epilepsy, approving diazepam nasal spray, branded as Valtoco, for the short-term treatment of seizure clusters in patients aged 2 years and older. This decision expands the previous indication, which was limited to patients aged 6 years and older, offering new hope for younger children suffering from this challenging condition.
Seizure clusters, also known as acute repetitive seizures, are defined as multiple seizures occurring in quick succession, often differing from a patient’s typical seizure pattern. Such episodes can pose severe risks, including the potential for status epilepticus if not treated promptly. According to the Epilepsy Foundation, timely intervention is crucial, as prolonged clusters can lead to increased complications.
The nasal spray formulation of Valtoco utilizes a proprietary absorption enhancement technology called INTRAVAIL, which allows for noninvasive delivery of diazepam. This method has been previously recognized by the FDA as clinically superior to the traditional rectal gel formulation of diazepam, which has historically been the standard treatment for acute seizure episodes. The FDA’s endorsement of Valtoco not only reinforces its efficacy and safety profile but also grants it orphan drug exclusivity, highlighting its importance in treating a niche yet critical patient population.
Dr. Eric Segal, the director of Pediatric Epilepsy at Northeast Regional Epilepsy Group and Hackensack University Medical Center, expressed optimism regarding the approval. “The FDA's decision to approve Valtoco for use in early childhood highlights the established balanced safety and efficacy profile,” he stated. “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.”
The approval of Valtoco was underpinned by data from a phase 1/2a clinical study that assessed the safety and pharmacokinetics of the nasal spray among children aged 2 to 5 years diagnosed with epilepsy. This open-label study involved 35 pediatric patients, with a mean age of 3.9 years, who were monitored over a 180-day safety period. Caregivers administered the nasal spray as needed, and patients maintained diaries to document seizure occurrences and medication use.
During the study, a total of 299 doses were administered across three dosage levels: 5 mg, 10 mg, and 15 mg. The results indicated that while 24 patients experienced treatment-emergent adverse events, none were deemed serious or treatment-related. The most common side effects included somnolence, headache, and nasal discomfort. Notably, only 7.9% of patients reported nasal irritation, suggesting that the nasal spray is generally well-tolerated.
Dr. Jurriaan M. Peters, director of the localization laboratory in the division of epilepsy and clinical neurophysiology at Boston Children’s Hospital, emphasized the significance of this approval. “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,” he noted. “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.”
The implications of Valtoco’s approval extend beyond individual patients. Approximately 3.4 million people in the United States are living with epilepsy, including around 400,000 children. The introduction of a non-invasive treatment option like Valtoco could significantly enhance the management of seizure clusters, which have historically been difficult to control.
Neurelis, Inc., the company behind Valtoco, expressed gratitude to the families and patients who participated in the clinical trials that facilitated this milestone. Craig Chambliss, the founder and CEO of Neurelis, stated, “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.”
As the medical community continues to seek innovative solutions for managing epilepsy, Valtoco represents a promising step forward in providing effective, accessible treatments for children experiencing seizure clusters. With its approval, families now have a new tool to manage these challenging episodes, potentially improving outcomes and quality of life for countless young patients.
