2024.12.06
source：NEURELIS San Diego, CA – December 6, 2024 – Neurelis, Inc., today announced details of its presentations at the American Epilepsy Society (AES) Annual Meeting to be held December 6-10 in Los Angeles. The collection of ten posters highlights analyses of immediate-use seizure medication for treatment of seizure clusters. A wide variety of presentations include pharmacokinetics (PK) and safety analyses from the study of VALTOCO® (diazepam nasal spray) for the treatment of seizure clusters in patients with epilepsy aged 2-5 years, time to treatment and seizure cluster termination, treatment of prolonged seizures within a cluster, as well as potential drug effects beyond the immediate treated seizure cluster, implications of seizure clusters in the epilepsy monitoring unit, and development of evidence-based self-management criteria encompassing the use of immediate-use seizure medication.
“The AES Annual Meeting is an important opportunity for the epilepsy community to engage with each other on critical research and the latest advancements in the field,” said Adrian L. Rabinowicz, MD, Neurelis Chief Medical Officer. “We are proud to have such a strong set of pre-clinical and clinical presentations to share at this year’s meeting and look forward to connecting with healthcare practitioners, researchers, people with epilepsy, and care partners as we share a common mission to improve quality of life for people with epilepsy.”
Neurelis’ presentations at the Annual Meeting include the following.
Poster Session 1: December 7th, 12:00 PM – 2:00 PM ET
● Exploring Proposed Recommendations for Acute Cluster Treatment and Rapid and Early Seizure Termination Using Data from a Long-Term Safety Study of Diazepam Nasal SprayPresentation of data from the long-term safety study of diazepam nasal spray explores clinical evidence supporting recent expert consensus recommendations for medications appropriate for acute cluster treatment and for rapid and early seizure termination. The study objective was to examine a single immediate-use seizure medication for both acute cluster treatment and rapid and early seizure termination, with the potential to simplify patient care. Findings in the study demonstrate the benefit of diazepam nasal spray use for both termination of acute seizure clusters and prolonged seizures within clusters.
● Effect of Diazepam Intervention on Seizure-Cluster Expression in a Rat Model of EpilepsyThis poster shares data from a preclinical study investigating the possible impact of diazepam on seizure cluster expression in a post-kainic acid status epilepticus (KASE) rat model of chronic epilepsy. Results demonstrated that in this rat model, expression was consistent with potential disease-modifying effects on seizure clusters, including reduced seizure severity, interseizure interval, and stability within clusters, supporting further exploration of the potential disease-modifying effect of diazepam.
● Is Disease Modification in Seizure Clusters Possible? Results From the Long-Term Safety Study of Diazepam Nasal Spray A subgroup analysis of patients treated with diazepam nasal spray in a long-term open label safety study was evaluated to assess the intervals of treated seizure clusters (SEIVAL) over time as a potential indicator of disease modification. Results were consistent across subgroups based on age, sex, with and without change in concomitant medications, pediatric developmental/epileptic encephalopathies, with prolonged seizures, and with self-administration of diazepam nasal spray.
Poster Session 2: December 8th, 12:00 PM – 2:00 PM ET
● Treatment of Prolonged Seizure with Diazepam Nasal Spray: A Post Hoc Cohort AnalysisProlonged seizures within a seizure cluster, treated with diazepam nasal spray within 5-15 minutes of seizure onset, were investigated in a post hoc subgroup analysis of a Phase 3 long-term safety study. Across age, seizure type, and high treatment usage subgroups, similar times to seizure termination were observed. Results also show low use of second doses demonstrating preserved effectiveness in seizures that have become prolonged within a cluster.
● Pharmacokinetic Characteristics of Diazepam Nasal Spray in Children with Epilepsy 2 to 5 Years of AgeThe PK of diazepam nasal spray for treatment of seizure clusters in patients 2-5 years of age was evaluated. Results demonstrated that diazepam nasal spray was readily absorbed with similar exposure for patients aged 2-3 years and 4-5 years and also showed a consistent PK profile in 2-5 year olds with that of older children and adults aged 6-59 years.
● 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 StudySafety of diazepam nasal spray in patients aged 2-5 years was assessed through the 180-day open-label safety period. Overall, the safety profile of diazepam nasal spray was similar to that established for older children and adults.
● Second Dose Use as a Proxy for Effectiveness of Diazepam Nasal Spray in Patients with Epilepsy Aged 2-5 Years: Interim Results from a Phase 1/2a StudyThe effectiveness of diazepam nasal spray in the 2-5 years age group was evaluated using the proportion of second doses (doses given within 24 hours of initial doses) used to treat seizure clusters as a proxy for effectiveness. Results showed comparable rates of seizure clusters treated with second doses among pediatric patients aged 6-17 years in the long-term safety study of diazepam nasal spray, supporting the effectiveness of the age-based dosing regimen in patients aged 2-5.
● Potential Adverse Events of Clinical Interest with Use of Diazepam Nasal Spray in Children: Interim Results from an Ongoing Open-Label, Pharmacokinetic and Safety StudyTreatment-emergent adverse events (TEAEs) of clinical interest associated with the use of benzodiazepines were assessed in patients aged 2-5 who received at least one dose of diazepam nasal spray through the 180-day open-label safety period of a Phase 1/2a pharmacokinetic and safety study. Treatment-related TEAEs of clinical interest were uncommon and primarily nasal, with none reported in more than one patient. There were no clinically significant changes in vital signs or laboratory values and no new safety signals of clinical interest in children aged 2-5 years.
● Immediate-Use Seizure Medication for Acute Repetitive Seizures in the Epilepsy Monitoring Unit: Experiences from an Expert PanelA pilot survey of a group of expert epileptologists discussed practice experience with immediate-use seizure medications (ISM, rescue) before, during, and after long-term video-electroencephalogram monitoring (LTVEM) in the epilepsy monitoring unit (EMU). Results highlighted the importance of expanding this research and the potential value of expert guidelines.
● Development of Self-Management Tool for Individuals with Seizure ClustersThe study presents an ongoing study focused on self-management for people with epilepsy and a history of negative health events (SMART), an evidence-based program investigating integration of immediate-use seizure medications (rescue medication) into the self-management program.
About Neurelis
Neurelis, Inc., is a neuroscience company focused on the development and commercialization of therapeutics for the treatment of epilepsy and neurologic disorders characterized by high unmet medical need. The FDA has approved Neurelis’ VALTOCO® (diazepam nasal spray) as an acute treatment of intermittent, stereotypic episodes of frequent seizure activity (i.e., seizure clusters, acute repetitive seizures) that are distinct from an individual’s usual seizure pattern in adult and pediatric patients 6 years of age and older. VALTOCO is a proprietary formulation of diazepam incorporating the science of INTRAVAIL®, a transmucosal absorption enhancement technology that enables the noninvasive delivery of a broad range of protein, peptide and small-molecule drugs. For more information on VALTOCO, please visit www.valtoco.com. For the latest scientific information on VALTOCO, please visit http://www.neurelismedicalaffairs.com/. Neurelis is also developing NRL-1004, an investigational, Phase 1 stage intranasal olanzapine for treatment of acute agitation episodes associated with schizophrenia and bipolar disorder. In addition, Neurelis is also developing NRL-1049 (previously known as BA-1049), an investigational, Phase 1 new chemical entity Rho kinase (ROCK) inhibitor, for the treatment of cerebral cavernous malformations (CCMS), a rare disorder of the central nervous system (CNS). For more information on Neurelis, please visit www.neurelis.com.
