NEURELIS ANNOUNCES 16 POSTER PRESENTATIONS AT THE ANNUAL MEETING OF THE AMERICAN EPILEPSY SOCIETY
- Subgroup analyses from the long-term safety study of VALTOCO® (diazepam nasal spray) demonstrated favorable safety and tolerability results in children (6-11 years of age), adolescents (12-17 years of age) and adults who experience seizure clusters
- Safety and effectiveness results for VALTOCO remained consistent in subgroups of patients, including subgroups of patients with concomitant clobazam use, epileptic encephalopathies and seasonal allergies/rhinitis
- Patients using VALTOCO reported numerical improvements in some Quality of Life scores in the long-term safety study
SAN DIEGO, CA — December 2, 2021 — Neurelis, Inc. will present a collection of 16 posters describing safety, tolerability and effectiveness results observed in trials evaluating VALTOCO® (diazepam nasal spray), and clinical trials designed to evaluate VALTOCO as a potential rescue therapy in patient groups with unmet needs at the annual meeting of the American Epilepsy Society December 3-7 in Chicago.
Enrique Carrazana, M.D., Neurelis Chief Medical Officer, said the long-term clinical study of VALTOCO® covered 4,390 seizure events and provided supportive evidence of its safety, effectiveness and tolerability. VALTOCO was approved by the U.S. Food and Drug Administration (FDA) in 2020 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 adult and pediatric patients 6 years of age and older. In granting VALTOCO Orphan Drug Exclusivity, the FDA recognized VALTOCO’s intranasal route of administration as clinically superior to the previously approved standard-of-care treatment (DIASTAT®, a rectal gel formulation of diazepam).
“Since the FDA approval of VALTOCO, we have presented 65 posters at national and international scientific meetings,” Dr. Carrazana said. “The clinical evidence supporting VALTOCO’s utility continues to mount and we believe underscores the need for this patient population to have a convenient, reliable, on-the-go treatment for seizure clusters.”
Adrian L. Rabinowicz, M.D., Senior Vice President of Clinical Development and Medical Affairs, noted that these analyses from the completed long-term Phase 3, open-label, repeat-dose safety study of VALTOCO identified similarities in safety and effectiveness results observed between pediatric (ages 6 and over), adolescent and adult populations enrolled in the study. He added that the safety and effectiveness results observed for VALTOCO also remained consistent in analyses evaluating certain subgroups of patients, including but not limited to patients with concomitant clobazam use, epileptic encephalopathies and seasonal allergies/rhinitis. “Patient and caregiver reporting suggested that VALTOCO was easy to use and rapid to administer during the study,” Dr. Rabinowicz commented. He added that no new safety signals emerged from the study, including no reports of respiratory depression. Patients enrolled in the study did not appear to develop a tolerance to repeated intermittent use of VALTOCO over time.
The long-term safety study of VALTOCO, Dr. Rabinowicz said, also showed maintenance in patient-reported Quality of Life in Epilepsy scores, including numerical improvement in the seizure worry and social functioning subscale scores.
Additional posters to be presented focus on the following:
- A study-design poster that describes a new open-label pharmacokinetic and safety study evaluating diazepam nasal spray as a potential rescue therapy for seizure clusters in children aged 2 to 5 years. (Neurelis announced the initation of the Phase 1/2a clinical program, named Stellina™, in September.) VALTOCO (diazepam nasal spray) is approved by the FDA for the acute treatment of intermiitent, stereotypic episodes of frequent seizure activity in patients with epilepsy 6 years of age and older. VALTOCO is under investigation for the use in children under 6 years; the efficacy and safety for this use have not been demonstrated
- Additional analyses from the long-term safety study, including analyses of administration of second doses of diazepam nasal spray within 4 hours of the first dose using a population pharmacokinetic model and descriptive evaluations. Per the VALTOCO prescribing information, a second dose may be given at least 4 hours after the initial dose, if required. The use of a second dose within 4 hours has not been approved by the FDA
- A late-breaking presentation describing preliminary results from a survey of school nurses on current practices and experience treating seizure clusters in the school setting
The details for the poster presentations are as follows and are available online to review at the American Epilepsy Society website.
Diazepam Nasal Spray (Valtoco®) Second Dose Administration Within 4 Hours: A Population Pharmacokinetic (PK) Analysis
Study Design of an Open-Label Pharmacokinetic and Safety Trial of Diazepam Nasal Spray (Valtoco®) in Children 2–5 Years Old With Seizure Clusters
Results for the Quality of Life in Epilepsy Scale From a Long-Term Safety Study of Diazepam Nasal Spray for Seizure Clusters
Adults Self-Administering Diazepam Nasal Spray for Seizure Clusters: Results on the Quality of Life in Epilepsy Scale From a Phase 3, Open-Label, Repeat-Dose, Safety Study
Lack of Tolerance With Diazepam Nasal Spray for Seizure Clusters After Long-term Use: Final Results From a Phase 3, Open-label, 12-month Repeat Dose Safety Study
Assessment of Study Endpoints for Patients Discontinuing From a Phase 3, Long-Term, Open-Label, Repeat-Dose, Safety Study of Diazepam Nasal Spray for Acute Treatment of Seizure Clusters
QoL and Treatment Satisfaction in a Long-Term Safety Study of Diazepam Nasal Spray for Seizure Clusters as Assessed by Patients and Their Caregivers
Timing to Administration and Ease of Dosing of Diazepam Nasal Spray Rescue Therapy for Seizure Clusters: Results From a Phase 3, Long-Term Open-Label, Repeat-Dose Safety Study
Safety and Effectiveness of Diazepam Nasal Spray in Pediatric Patients with Epileptic Encephalopathy: Final Results From a Phase 3, Open-Label, Repeat-Dose Safety Study
Lack of Impact of Seasonal Allergies or Rhinitis History on the Safety of Diazepam Nasal Spray in Patients With Seizure Clusters: Final Results From a Long-Term, Phase 3, Open-Label, Repeat-Dose Safety Study
Evaluating Tolerability Endpoints Relevant to Clinicians and Patients in a Long-Term, Phase 3, Open-Label Repeat-Dose Safety Study of Diazepam Nasal Spray in Patients With Seizure Clusters
Development of a School Nurse Survey to Understand Current Practices, Barriers, and Needs for Treatment of Seizure Clusters in a School Setting
Quality of Life in Epilepsy Scale for Frequent and Infrequent Users of Diazepam Nasal Spray for Seizure Clusters in a Phase 3, Open-Label, Repeat-Dose Safety Study
Safety and Time to Second Doses in Age Subgroups of Patients With Seizure Clusters Treated With Diazepam Nasal Spray in a Phase 3, Open-Label, Repeat-Dose Safety Study
Safety of a Second Dose of Diazepam Nasal Spray Within 4 Hours in Patients With Seizure Clusters: Final Results From a Long-Term, Phase 3, Open-Label, Repeat-Dose Safety Study
Evaluation of Diazepam Nasal Spray in Patients with Seizure Clusters Concomitantly Receiving Clobazam: A Subgroup Analysis from a Completed Phase 3, Long-term, Open-label Safety Study
Neurelis, Inc., is a commercial-stage 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’s 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 to VALTOCO, Neurelis is developing NRL-2 for intermittent use to control acute panic attacks, NRL-3 as a noninvasive acute therapy to stop seizures that have progressed to status epilepticus, and NRL-4 as a noninvasive rescue therapy to address the escalation of acute agitation symptoms associated with schizophrenia and bipolar 1 mania in adults. In addition, Neurelis is developing NRL-1049 (previously known as BA-1049), an investigational, pre-clinical 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 www.neurelismedicalaffairs.com.
Important Safety Information about VALTOCO:
VALTOCO® (diazepam nasal spray) is indicated for the acute treatment of intermittent, stereotypic episodes of frequent seizure activity (ie, 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.
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.
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.
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, for additional important safety information.