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

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

NEURELIS ANNOUNCES FDA APPROVAL FOR IMMEDIATE USE SEIZURE MEDICATION VALTOCO (DIAZEPAM NASAL SPRAY) IN AGES 2 TO 5 (PRNewswire) - "Neurelis, Inc., today announced that the U.S. Food and Drug Administration (FDA) has approved VALTOCO (diazepam nasal spray) for short-term treatment of seizure clusters (also known as 'acute repetitive seizures') that are different from a person's normal seizure pattern in people 2 years of age and older. VALTOCO is a proprietary formulation which utilizes an absorption enhancement technology, INTRAVAIL, to enable the noninvasive, enhanced intranasal delivery of diazepam....Data from the phase 1/2a clinical study evaluating safety and pharmacokinetics demonstrated that VALTOCO is safe and effective with easy nasal administration for patients aged 2 years and older who have episodes of frequent seizures."

FDA approval • CNS Disorders

Exploring Proposed Recommendations for Acute Cluster Treatment and Rapid and Early Seizure Termination Using Data From a Long-Term Safety Study of Diazepam Nasal Spray (P12-9.004). (PubMed, Neurology) - "Safety data for diazepam nasal spray were similar to that for diazepam rectal gel. Rabinowicz has stock in Neurelis, Inc. Disclaimer: Abstracts were not reviewed by Neurology® and do not reflect the views of Neurology® editors or staff."

Journal • CNS Disorders • Epilepsy

Treatment of Status Epilepticus At and After T1 With Diazepam Nasal Spray: A Combined Cohort Analysis (PRNewswire) - "A post hoc analysis of pooled data from two long-term, open-label safety studies was conducted to investigate treatment of early SE episodes in patients with epilepsy aged 2-65 years. Early SE episodes were defined as seizures continuing after Time Point 1 (t1) (5 minutes for generalized seizures; 10 minutes for focal and unclassified seizures). For patients with seizure episodes reaching t1 (671 events of t1 SE in 97 patients), diazepam nasal spray provided timely control of SE episodes. Overall, safety was generally consistent with the established profile of diazepam nasal spray, and most episodes did not result in hospitalization due to serious treatment emergent adverse events (TEAEs) for SE. Additionally, in a responder analysis, the majority of early SE seizures terminated prior to Time Point 2 (when neuronal injury may occur: 30 and 60 minutes for generalized and focal seizures, respectively)."

Retrospective data • CNS Disorders • Epilepsy

Treatment of Prolonged Seizure with Diazepam Nasal Spray: A Post Hoc Cohort Analysis (PRNewswire) - "To assess effectiveness of diazepam nasal spray in treating prolonged seizures (5-15 minutes post onset) within seizure clusters (727 events), a post hoc subgroup analysis of data from the long-term safety study of diazepam nasal spray in patients aged 6-65 years was conducted. Across age, seizure type, and high treatment usage subgroups, generally similar times to seizure termination were observed. Use of second doses within 24 hours for prolonged seizures was low (9.3%) and generally consistent across subgroups, demonstrating preserved first-dose effectiveness in seizures that have become prolonged."

Retrospective data • CNS Disorders • Epilepsy

Exploring Proposed Recommendations for Acute Cluster Treatment and Rapid and Early Seizure Termination Using Data from a Long-Term Safety Study of Diazepam Nasal Spray (PRNewswire) - P=NA | N=163 | "Clinical data from the long-term safety study of diazepam nasal spray in patients aged 6-65 years was analyzed to determine whether it could support the recent expert consensus recommendations to terminate acute clusters and ongoing seizures that are expected to be prolonged. The effectiveness of diazepam nasal spray to prevent further seizures in a cluster was demonstrated by the low use of second doses across 24 hours. Rapid and early seizure termination was demonstrated in a dataset of 3225 administrations. Notably, for treatment within 5 minutes of seizure onset, rapid time to seizure termination reinforced the importance of early treatment."

Clinical data • Epilepsy

Treatment of Status Epilepticus At and After T1 With Diazepam Nasal Spray: A Combined Cohort Analysis (AAN 2025) - "In patients 2–65y with seizure episodes reaching T1, diazepam nasal spray provided consistent control, and the majority of these episodes were not associated with hospitalization as serious TEAEs. Diazepam nasal spray demonstrated safety and tolerability in patients 2–65y."

CNS Disorders • Epilepsy

The FORESITE Study: FOREcasting Seizures to Initiate ThErapy – Technical Design, Hardware, and Algorithms (AAN 2025) - "Seizure alerts prompt administration of intranasal diazepam, with the goal of preventing seizures before they begin. Seizure forecasting to guide medication is feasible."

CNS Disorders • Epilepsy

Treatment of Prolonged Seizure With Diazepam Nasal Spray: A Post Hoc Cohort Analysis (AAN 2025) - "If treatment is delayed (ie, a prolonged seizure within a SC), diazepam nasal spray rapidly terminates the SC with high first-dose effectiveness and a well-characterized safety profile. Diazepam nasal spray controls SCs when used promptly and when seizures are prolonged."

Retrospective data • CNS Disorders • Depression • Epilepsy • Pediatrics • Psychiatry

Exploring Proposed Recommendations for Acute Cluster Treatment and Rapid and Early Seizure Termination Using Data From a Long-Term Safety Study of Diazepam Nasal Spray (AAN 2025) - "Data from the long-term safety study of diazepam nasal spray demonstrate its benefit in immediate use for both prevention of further seizures in SCs (ACT) and termination of an acute SC and PS in a cluster (REST)."

Clinical • CNS Disorders • Epilepsy

Development of a self-management tool for individuals with seizure clusters: Trial design and methodological report. (PubMed, Epilepsy Behav) - "Integrating RM into an evidence-based epilepsy self-management curriculum offers a comprehensive care package with potential to improve care for PWE with seizure clusters."

Journal • CNS Disorders • Depression • Epilepsy • Psychiatry

Seizure Clusters and Rescue Medication: What Does Youtube Offer? (AES 2024) - "FDA-approved treatment recommendations included rectal Diastat, intranasal Nayzilam, or intranasal Valtoco... Finding informative YouTube videos on seizure cluster management is difficult. While several videos appeared to be effective as patient and provider education, applying less specific terminology returned unrelated or unhelpful videos. Healthcare institutions and pharmaceutical companies should produce brief, helpful videos of rescue therapy and arm patients with search terms to facilitate better navigation of educational resources."

CNS Disorders • Epilepsy

Neurologists Improve Their Knowledge, Competence, and Confidence of Seizure Action Plans and Seizure Rescue Medications Following Participation in an Online Certified Medical Education Program (AES 2024) - "The following areas showed significant (P < .05) pre- vs post-educational improvements: information that should always be included in an acute seizure action plan; clinically relevant differences between intranasal diazepam and intranasal midazolam; and the individualized selection of an appropriate seizure rescue medication for a patient with seizure clusters. The results indicated that this CME-certified 50-minute video discussion between physician experts was effective at improving awareness among neurologists regarding both seizure action plans and seizure rescue medications. Future educational efforts should continue to address the core features of seizure action plans as well as strategies to personalize the selection of seizure rescue medications."

CNS Disorders • Cognitive Disorders • Epilepsy