News Releases

Additional analyses from phase 3, long-term, open-label, repeat-dose study of VALTOCO^®

Findings show intermittent nasal spray effectiveness in a fed/fasted state or with cannabidiol usage

Retrospective evaluation of time between seizures and administration of various rescue medications

SAN DIEGO, Oct. 4, 2023 /PRNewswire/ -- Neurelis, Inc., today announced additional findings from the post hoc analysis of the long-term phase 3 safety study of VALTOCO^® (diazepam nasal spray) in a pediatric population, aged 6-17 years, as well as an analysis of real-world data on impact of administration of rescue medication on seizure timing.  A total of four posters will be presented at the 52nd Child Neurology Society Annual Meeting in Vancouver, BC, Canada, October 4 – 7, 2023. The Child Neurology Society's mission is to raise awareness about the importance of child neurologists and the health needs of children with chronic neurological conditions.

"Our data continues to add to the growing body of evidence demonstrating the safety and efficacy of diazepam nasal spray in pediatric patient populations, similar to what has been reported in adults," said Adrian L. Rabinowicz, M.D., Neurelis Chief Medical Officer. "This data brings us one step closer to addressing seizures acutely to improve the quality of life for people with epilepsy."

"We are pleased to present these findings to help the child neurology community identify advanced treatment options," said Enrique Carrazana, Neurelis Senior Vice President, Strategic Initiatives. "While further research is needed, we believe the clinical and real-world data generated to date will help people with epilepsy understand the role that acute seizure management plays in helping to manage their seizures clusters and return to their daily lives."

Following are the presentation details, which will be held on Thursday, October 5^th from 12:30 PM – 2:00 PM & 5:30 PM – 7:00 PM:

• Effectiveness of Diazepam Nasal Spray Does Not Vary Across Times of Day in Pediatric Patients with Seizure Clusters (POSTER #59)
  
  In pediatric patients (aged 6-17 years), analysis of time of treatment as a proxy for circadian and behavioral variables (e.g., fed/fasted state) found no clear association between time of day and administration of second doses of diazepam nasal spray to treat seizure clusters. These findings indicate consistent treatment effectiveness throughout the day and night and suggest that absorption of diazepam nasal spray is not affected by the fed/fasted state.

• Safety and Effectiveness of Diazepam Nasal Spray with Concomitant Cannabidiol: Post Hoc Analysis of Pediatric Patients from a Phase 3 Safety Study (POSTER #76)
  
  Daily treatment regimens for seizures may include use of an FDA-approved, highly purified oral-solution cannabidiol (CBD). Analysis of the pediatric cohort (aged 6-17 years) from the Phase 3 study of diazepam nasal spray who also received a form of CBD, showed overall safety and effectiveness profiles of diazepam nasal spray similar to patients not receiving CBD. These results support concomitant use of CBD in pediatric patients.

• Rapid Initiation of Rescue Treatment with Diazepam Nasal Spray Leads to Faster Seizure Termination in Pediatric Patients with Seizure Clusters (POSTER #80)
  
  Data from the Phase 3 study of diazepam nasal spray demonstrates among pediatric patients (aged 6-17 years) experiencing seizure clusters, shorter time to start of treatment was associated with shorter time to seizure cessation and overall shorter seizure duration, suggesting that prompt treatment may provide benefit.  Further research is needed to clarify the relationship between treatment timing and seizure termination time.

• Real-World Retrospective Outcomes with Inter-Seizure Cluster Interval and the Number of Seizures per Cluster Following Rescue Medication Administration (POSTER #82)
  
  Evaluation of treated and untreated seizure clusters from a large, online database of patient/caregiver-reported seizures shows that when a rescue medication is given, the time between seizure clusters tends to be longer and treatment is associated with fewer seizures per cluster.

VALTOCO, a nasal spray for acute treatment of episodes of frequent seizure activity in adult and pediatric patients 6 years of age and older, was approved by the U.S. Food and Drug Administration (FDA) on Jan. 10, 2020.

About Neurelis

Neurelis, Inc., is a neuroscience company focused on the development and commercialization of therapeutics for the treatment of epilepsy and orphan neurologic disorders characterized by high unmet medical need. In 2020, the FDA 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^®. Intravail's transmucosal absorption enhancement technology enables the noninvasive delivery of a broad range of protein, peptide and small-molecule drugs. In its approval of VALTOCO, the U.S. Food and Drug Administration also granted Neurelis Orphan Drug Exclusivity and recognized VALTOCO's intranasal route of administration as a clinically superior contribution to patient care over the previously approved standard-of-care treatment (a rectal gel formulation of diazepam). For more information on VALTOCO, please visit www.valtoco.com. In addition, Neurelis is developing NRL-1049 (previously known as BA-1049), an investigational, Phase I stage small molecule 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. For the latest scientific information on VALTOCO, please visit http://www.neurelismedicalaffairs.com/.

Important Safety Information about VALTOCO:

Indication

VALTOCO^® (diazepam nasal spray) is indicated for the acute treatment of intermittent, stereotypic episodes of frequent seizure activity (i.e., seizure clusters, acute repetitive seizures) that are distinct from a patient's usual seizure pattern in patients with epilepsy 6 years of age and older.

WARNING: RISKS FROM CONCOMITANT USE WITH OPIOIDS; ABUSE, MISUSE, AND ADDICTION; and DEPENDENCE AND WITHDRAWAL REACTIONS

• Concomitant use of benzodiazepines and opioids may result in profound sedation, respiratory depression, coma, and death. Reserve concomitant prescribing of these drugs for patients for whom alternative treatment options are inadequate. Limit dosages and durations to the minimum required. Follow patients for signs and symptoms of respiratory depression and sedation.
• The use of benzodiazepines, including VALTOCO, exposes users to risks of abuse, misuse, and addiction, which can lead to overdose or death. Abuse and misuse of benzodiazepines commonly involve concomitant use of other medications, alcohol, and/or illicit substances, which is associated with an increased frequency of serious adverse outcomes. Before prescribing VALTOCO and throughout treatment, assess each patient's risk for abuse, misuse, and addiction.
• The continued use of benzodiazepines may lead to clinically significant physical dependence. The risks of dependence and withdrawal increase with longer treatment duration and higher daily dose. Although VALTOCO is indicated only for intermittent use, if used more frequently than recommended, abrupt discontinuation or rapid dosage reduction of VALTOCO may precipitate acute withdrawal reactions, which can be life-threatening. For patients using VALTOCO more frequently than recommended, to reduce the risk of withdrawal reactions, use a gradual taper to discontinue VALTOCO. 

Contraindications: VALTOCO is contraindicated in patients with:

• Hypersensitivity to diazepam
• Acute narrow-angle glaucoma

Central Nervous System (CNS) Depression
Benzodiazepines, including VALTOCO, may produce CNS depression. Caution patients against engaging in hazardous activities requiring mental alertness, such as operating machinery, driving a motor vehicle, or riding a bicycle, until the effects of the drug, such as drowsiness, have subsided, and as their medical condition permits.

The potential for a synergistic CNS-depressant effect when VALTOCO is used with alcohol or other CNS depressants must be considered, and appropriate recommendations made to the patient and/or care partner.

Suicidal Behavior and Ideation
Antiepileptic drugs (AEDs), including VALTOCO, increase the risk of suicidal ideation and behavior. Patients treated with any AED for any indication should be monitored for the emergence or worsening of depression, suicidal thoughts or behavior, and/or unusual changes in mood or behavior.

Glaucoma
Benzodiazepines, including VALTOCO, can increase intraocular pressure in patients with glaucoma. VALTOCO may only be used in patients with open-angle glaucoma only if they are receiving appropriate therapy. VALTOCO is contraindicated in patients with narrow-angle glaucoma.

Neonatal Sedation and Withdrawal Syndrome
Use of VALTOCO late in pregnancy can result in sedation (respiratory depression, lethargy, hypotonia) and/or withdrawal symptoms (hyperreflexia, irritability, restlessness, tremors, inconsolable crying, and feeding difficulties) in the neonate. Monitor neonates exposed to VALTOCO during pregnancy or labor for signs of sedation and monitor neonates exposed to VALTOCO during pregnancy for signs of withdrawal; manage these neonates accordingly.

Risk of Serious Adverse Reactions in Infants due to Benzyl Alcohol Preservative
VALTOCO is not approved for use in neonates or infants. Serious and fatal adverse reactions, including "gasping syndrome," can occur in neonates and low-birth-weight infants treated with benzyl alcohol–preserved drugs, including VALTOCO. The "gasping syndrome" is characterized by central nervous system depression, metabolic acidosis, and gasping respirations. The minimum amount of benzyl alcohol at which serious adverse reactions may occur is not known.

Adverse Reactions
The most common adverse reactions (at least 4%) were somnolence, headache, and nasal discomfort.

Diazepam, the active ingredient in VALTOCO, is a Schedule IV controlled substance.

To report SUSPECTED ADVERSE REACTIONS, contact Neurelis, Inc. at 1-866-696-3873 or FDA at 1-800-FDA-1088 (www.fda.gov/medwatch).

Please read full Prescribing Information, including Boxed Warning.

Contacts:

Neurelis:
Brittany Bradrick, Chief Operating Officer and Chief Financial Officer, +1 858 251 2135

Media:
Glenn Silver, FINN Partners, +1 646 871 8485

SOURCE Neurelis, Inc.