Valtoco (diazepam intranasal) / Neurelis, Aculys Pharma - LARVOL DELTA

Safety and Local Tolerability of Diazepam Nasal Spray for Children With Epilepsy Aged 2-5 Years: Final Results of a Phase 1/2a Trial. (PubMed, J Child Neurol) - P1/2 | "A long-term safety study in patients aged 6-65 years found a safety profile similar to diazepam rectal gel. No serious treatment-related TEAEs or TEAEs leading to discontinuation/death occurred. The safety profile aligns with patients aged ≥6 years, supporting use in this population.(ClinicalTrials.gov identifier: NCT05076838)."

Journal • P1/2 data • CNS Disorders • Epilepsy

Outcomes of out-of-hospital treatment of impending tonic-clonic status epilepticus with diazepam nasal spray: A retrospective combined cohort analysis. (PubMed, Epilepsia) - "These findings support the safety and effectiveness of diazepam nasal spray for treating episodes of tonic-clonic SE and strengthen the evidence of the benefits of immediate-use antiseizure medication for seizure emergencies, including early SE."

Journal • Retrospective data • CNS Disorders • Epilepsy

Clinical insights: an update on transmucosal absorption with a focus on dodecyl maltoside. (PubMed, Expert Opin Drug Deliv) - "These new treatment options offer effectiveness and ease of use for patients and caregivers. DDM and closely related excipients have many promising opportunities for future applications, facilitating absorption across nasal and other epithelia membranes."

Journal • Review • CNS Disorders • Epilepsy

Seizure Rescue Medication (RM) as Part of a Comprehensive Epilepsy Self-management Package of Care (clinicaltrials.gov) - P4 | N=31 | Active, not recruiting | Sponsor: University Hospitals Cleveland Medical Center | Trial completion date: Sep 2026 ➔ Dec 2026 | Trial primary completion date: Sep 2026 ➔ Dec 2026 | Recruiting ➔ Active, not recruiting

Enrollment closed • Trial completion date • Trial primary completion date • CNS Disorders • Epilepsy

Increased interval between seizure clusters across time in pediatric patients treated with the immediate-use seizure medication diazepam nasal spray. (PubMed, Epilepsia) - "These results corroborate those of the earlier post hoc analysis of data from patients 6 to 65 years of age who received diazepam nasal spray for seizure clusters. These findings suggest a beneficial long-term treatment effect of diazepam nasal spray beyond acute use as an ISM."

Journal • CNS Disorders • Epilepsy • Pediatrics

Healthcare Resource Utilization (HCRU) in Patients with Epilepsy (PWE): A Comparison of Diazepam Nasal Spray (DNS) vs No Use (AAN 2026) - "Concomitant benzodiazepines (eg, clonazepam, clobazam) and cannabidiol were more common among patients with DNS (P<0.001)...Midazolam and gabapentin were more common in patients without DNS (P<0.001)...However, they had significantly fewer inpatient and outpatient visits and lower readmission rate vs a matched cohort, supporting the role of DNS in improved health outcomes that reduce patient, caregiver, and provider burden. Ongoing analyses will further analyze HCRU of PWE with DNS compared with other ISMs or no ISM."

Clinical • HEOR • CNS Disorders • Epilepsy

Prehospital Treatment of Status Epilepticus (SE) with Diazepam Nasal Spray in Pediatric and Adult Patients with Epilepsy (AAN 2026) - "Conclusions Prehospital use of diazepam nasal spray in patients aged 2-65 years resulted in rapid termination of SE episodes with generalized and/or focal seizures. Few SE events required hospitalization."

Clinical • CNS Disorders • Epilepsy • Pediatrics

Systematic statistical analysis of change in SEIzure interVAL with diazepam nasal spray supports this novel clinical endpoint for immediate-use seizure medication. (PubMed, Epilepsia) - P3 | "This systematically planned analysis expands on and reinforces the previous pragmatic analysis that introduced the SEIVAL metric. The present analysis provides a novel framework for future studies of intermittently administered ISMs to treat seizure clusters such as diazepam nasal spray."

Journal • CNS Disorders • Epilepsy

Safety and effectiveness of diazepam nasal spray in patients with Rett syndrome and seizure clusters: post hoc analyses from a long-term safety study and survey of severity and burden. (PubMed, Front Neurol) - P3 | "Diazepam nasal spray has safety and effectiveness profiles consistent with the full study population and was easy to use. ClinicalTrials.gov, NCT02721069."

Journal • Retrospective data • CNS Disorders • Developmental Disorders • Epilepsy • Movement Disorders • Pediatrics • Psychiatry

Seizure Rescue Medication (RM) as Part of a Comprehensive Epilepsy Self-management Package of Care (clinicaltrials.gov) - P4 | N=30 | Recruiting | Sponsor: University Hospitals Cleveland Medical Center | Trial completion date: Jan 2026 ➔ Sep 2026 | Trial primary completion date: Jan 2026 ➔ Sep 2026

Trial completion date • Trial primary completion date • CNS Disorders • Epilepsy

Preclinical signal for a disease-modifying effect on seizure cluster severity with intermittent diazepam treatment. (PubMed, Epilepsia) - "Changes in several seizure cluster phenotypical parameters were suggestive of an enduring disease-modifying effect of diazepam, despite an apparent rebound effect of intermittent diazepam treatment on seizure frequency. Further study is warranted using a model incorporating a background antiseizure medication regimen to potentially attenuate the unexpected rebound seizures."

Journal • Preclinical • CNS Disorders • Epilepsy

Seizure Rescue Medication (RM) as Part of a Comprehensive Epilepsy Self-management Package of Care (clinicaltrials.gov) - P4 | N=30 | Recruiting | Sponsor: University Hospitals Cleveland Medical Center | N=43 ➔ 30

Enrollment change • CNS Disorders • Epilepsy

Temporal Patterns of Dosing and Seizure Cessation in Children Aged 2-5 Years: Final Results from a Phase 1/2a Study of Diazepam Nasal Spray (AES 2025) - P1/2 | "In children aged 2-5 years, early treatment of seizures with immediate-use diazepam nasal spray was associated with early seizure cessation and shorter overall seizure duration. Treatment within 5 minutes of seizure start showed a rapid onset from dose to seizure cessation. No new safety signals were observed."

Clinical • P1/2 data • CNS Disorders • Depression • Epilepsy • Psychiatry • Respiratory Diseases

Prehospital Treatment of Impending Status Epilepticus With Diazepam Nasal Spray (AES 2025) - "This pooled cohort analysis demonstrates that treatment with diazepam nasal spray provides consistent and rapid control of impending SE episodes treated in the prehospital setting in patients with epilepsy aged 2-17 and ≥18 years"

Clinical • CNS Disorders • Epilepsy

Interval Between Seizure Clusters (SEIzure interVAL) in Children Aged 2-5 Years: Final Analysis From a Phase 1/2a Study of Diazepam Nasal Spray (AES 2025) - P1/2 | "In children aged 2-5 years who used diazepam nasal spray to treat seizure clusters, the interval between treated seizures substantially lengthened over time in these small groups. The increase in SEIVAL in young children is consistent with results reported in older patients aged 6-65 years enrolled in a phase 3 study of diazepam nasal spray. These findings suggest a beneficial long-term treatment effect of diazepam nasal spray as an intermittent seizure medication."

Clinical • P1/2 data • CNS Disorders • Depression • Epilepsy • Psychiatry • Respiratory Diseases

Final, Long-Term Safety Results for Diazepam Nasal Spray in Patients Aged 2-5 Years From a Phase 1/2a Study (AES 2025) - P1/2 | "Diazepam nasal spray does not require positioning the patient, needs fewer steps to administer than diazepam rectal gel, and has an established safety profile in patients aged 6-17 y that is consistent with rectal diazepam in children ≥6 y and adults. The safety profile of diazepam nasal spray was generally consistent with that of older patients and confirms the safety profile of diazepam nasal spray and age- and weight-based dosing in this younger age group of patients aged 2-5 y."

Clinical • P1/2 data • CNS Disorders • Depression • Epilepsy • Psychiatry • Respiratory Diseases

Rapid Termination of Seizures in a Cluster: Minute-by-Minute Subgroup Analysis of Prompt Treatment With Diazepam Nasal Spray (AES 2025) - "The minute-by-minute analysis of time to administration of diazepam nasal spray and time to seizure termination in the first 5 min after onset of an SC shows that earlier administration is associated with earlier seizure termination across clinically relevant subgroups. In some subgroups, later timepoints included few treated seizures; however, the generally consistent association between time to treatment and seizure cessation suggests that caregivers identified and treated SC rather than self-limited seizures. These findings provide support for the recent expert consensus recommendation for REST."

CNS Disorders • Epilepsy

Second Dose Usage as a Proxy for Effectiveness of Diazepam Nasal Spray in Patients with Epilepsy Aged 2–5 Years: Final Results of a Phase 1/2a Study (AES 2025) - P1/2 | "In this study of diazepam nasal spray for seizure clusters in children aged 2–5 y, >85% of seizure events did not use a second dose within 24 hours of the first. This finding is consistent with studies in older children and adults (Figure) and supports the effectiveness of diazepam nasal spray in this population and the established 0.5 mg/kg dosing paradigm for diazepam. The low use of second doses may reduce patients' seizure burden and caregivers' treatment burden."

Clinical • P1/2 data • CNS Disorders • Depression • Epilepsy • Psychiatry • Respiratory Diseases

Caregiver Perceptions of Diazepam Nasal Spray Treatment in Children Aged 2-5 Years (AES 2025) - "Two diazepam formulations are approved by the US Food and Drug Administration for the treatment of SCs in patients with epilepsy aged ≥2 y: diazepam rectal gel and diazepam nasal spray. At the end of the 180-day period, caregivers reported that most patients recovered quickly and that SCs did not affect other responsibilities, were not stressful to the family, and were milder and fewer and that recovery improved with treatment. These insights into caregiver perceptions reinforce the value of appropriate SC management."

Clinical • CNS Disorders • Epilepsy

Examining Nasal and Respiratory Safety of Diazepam Nasal Spray and Device Suitability for Children With Epilepsy Aged 2-5 Years (AES 2025) - "Rationale: Diazepam nasal spray (Valtoco®) is approved for the treatment of seizure clusters in patients with epilepsy aged ≥2 y. In patients aged 6-65 y, a safety profile consistent with that of diazepam rectal gel has been demonstrated. Diazepam nasal spray demonstrated favorable local safety and tolerability profile in children aged 2-5 years, with no serious treatment-related TEAE (including respiratory depression), and a low rate of dosing errors comparable to that seen in studies in older children and adults. These findings support the dosing paradigm and the device's suitability in treating seizure clusters for this age group."

Clinical • CNS Disorders • Depression • Dermatology • Epilepsy • Psychiatry • Respiratory Diseases

QUANTIFYING THE THERAPEUTIC EFFECTS OF INTRANASAL DIAZEPAM ON NEURAL BIOMARKERS IN A CHRONIC PORCINE MODEL OF EPILEPSY (Neuroscience 2025) - "Administration of intranasal diazepam produced distinct and quantifiable effects on neural biomarkers. First, LFP beta band power showed a strong, dose-dependent reactivity to the drug, with a significant positive correlation between its elevation and blood diazepam concentration (Pearson's r = 0.654, p<0.001). Second, the medication demonstrated clear anticonvulsant activity, significantly decreasing interictal epileptiform discharge (IED) rates by 53.5% (95% CI [29.8 %, 72.6 %) compared to control days (p<0.001)."

Late-breaking abstract • Preclinical • CNS Disorders • Epilepsy • IR

Potential for Therapeutic Alteration of the Underlying Biology of Epilepsy. (PubMed, Biomedicines) - "A reduction in seizures over time (e.g., increase in responder rates) or prevention of epilepsy in susceptible individuals has been observed with therapies that target neurotransmission (cenobamate, cannabidiol, vigabatrin, and diazepam nasal spray) and inflammation (everolimus), though evidence is limited and in preliminary stages. Standard criteria and a definition of disease modification should be established. Importantly, given the heterogeneity of the epilepsies, syndrome- or seizure-specific methods and trial design would likely be required."

Journal • Review • CNS Disorders • Depression • Epilepsy • Gene Therapies • Inflammation • Psychiatry

Pharmacokinetics and 180-day safety of diazepam nasal spray in pediatric patients with epilepsy aged 2-5 years. (PubMed, Epilepsia) - "This study characterizes the PK of diazepam in patients 2-5 years of age and reports a safety profile consistent with older patients. Results demonstrate that the diazepam nasal spray drug-device combination is appropriate for drug delivery and absorption in these patients."

Journal • PK/PD data • CNS Disorders • Depression • Epilepsy • Pediatrics • Psychiatry

Pharmacokinetics Study of VALTOCO® in Pediatric Subjects With Epilepsy (clinicaltrials.gov) - P1/2 | N=35 | Completed | Sponsor: Neurelis, Inc. | Active, not recruiting ➔ Completed | Trial completion date: Oct 2024 ➔ Apr 2025 | Trial primary completion date: Aug 2023 ➔ Apr 2025

Trial completion • Trial completion date • Trial primary completion date • CNS Disorders • Epilepsy • Pediatrics

Exploring proposed recommendations for immediate-use seizure medication: Treating both cluster and prolonged seizures with diazepam nasal spray. (PubMed, Epilepsia Open) - "Study data showed that for most seizure clusters only 1 dose of diazepam nasal spray was used over 24 h (fitting ACT), and seizures were treated and ended quickly (fitting REST). One medicine for REST and ACT may make treatment simpler."

Journal • Review • CNS Disorders • Epilepsy