Prepare your patients to stop seizures in their tracks

VALTOCO 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 2 years of age and older.¹

VALTOCO offers rapid, reliable, ready seizure treatment

A 12-month, open-label, repeat-dose safety study of patients 6+ years of age found^*:

4-minute median time from VALTOCO administration to seizure cessation^2,*,†

2-minute median time to seizure cessation when VALTOCO was administered within the first 5 minutes³

Time to administer and onset of action

Median time to VALTOCO administration²

2-minute median time to administer VALTOCO from seizure onset (range, -1-750 minutes)

Median time to seizure cessation after receiving VALTOCO²

4-minute median time to seizure cessation after VALTOCO administration (range, -1-1151 minutes)

VALTOCO is most effective when administered early^*

When VALTOCO was administered early, within the first 5 minutes of seizure onset, the median time to seizure cessation was 2 minutes³

^*In patients experiencing episodes of frequent seizures despite daily antiseizure medication treatment.⁴
^†2-minute median time to seizure cessation following VALTOCO administration (range, 0-1440 min).³
^‡1-minute median time to VALTOCO administration (range, 0-4 min).³

87% of seizure episodes used a single dose of VALTOCO over a 24-hour period^4,*

89% of seizure episodes in patients aged 6 to 17 years⁵

Use of single doses of VALTOCO over 24 hours

Patients with Epilepsy

Percentage of seizure episodes for which a single dose of VALTOCO was used over the course of 24 hours (N=3,853)⁴

Proportion of patients using single or second doses

52% of patients (n=84) never used a second dose over a 12-month period⁶
48% of patients (n=79) received a second dose within the 24-hour period after the initial dose⁶
8 patients accounted for 46% (224/485) of second doses administered⁷

A majority of patients returned to their usual selves within 1 hour of administration of VALTOCO^8,‡

Treatment-related somnolence was reported in 1.8% of patients⁴

The number of seizure-free days between treated seizure clusters doubled over a 12-month period in patients using VALTOCO^9,§

Return to self and mean sedation levels

Time to return to usual self for patients after the most recent administration of VALTOCO (N=64)⁸

Overall mean sedation levels were low, mild, transient, and not considered clinically relevant¹⁰

Analysis of time between treated seizure clusters

Patients with Epilepsy

The number of days between treated episodes of frequent seizures nearly doubled in patients using VALTOCO over a 12-month period⁹

SEIVAL increased by 12.9 days over a 12-month period (n=76)⁹

Patients with Epilepsy

SEIVAL increased independent of concomitant medication change⁹

^*This was an exploratory analysis of a 12-month, open-label, repeat-dose safety study in patients 6+ years of age; the study did not have prespecified efficacy endpoints.⁴^†Median time to seizure cessation of 4 minutes (range, -1-1151 minutes).²^‡59% of patients returned to their usual selves within 60 minutes of administration of VALTOCO as recorded in patient and caregiver surveys.⁸^§SEIVAL was measured as the time between VALTOCO doses using seizure diary data from the open-label safety study. Seventy-six of the 163 patients (47%) who received ≥1 dose of VALTOCO in the study had ≥1 SEIVAL in each of Periods 1, 2, 3, and 4 and were included in the consistent cohort for Periods 1-4. Retreatments, defined as second doses given within 24 hours of the first doses, were eliminated from the analysis.⁹

This study represents one of the largest studies to date of treated episodes of frequent seizures¹¹

Only VALTOCO uses Intravail^® technology for rapid and reliable absorption of diazepam^12,13

VALTOCO was formulated to address the principal limitations of intranasal drug delivery. Intravail^® technology facilitates increased drug absorption across the nasal mucosa by increasing permeability of cell membranes and temporarily loosening tight junctions between cells, allowing the drug to pass through.¹⁴

Nearly complete absorption of VALTOCO with 97% bioavailability relative to intravenous diazepam^1,12,||

Therapeutic plasma levels of VALTOCO sustained for 24 hours^1,12

Predictable pharmacokinetics with low interpatient and intrapatient variability^1,13,17,||

VALTOCO demonstrated 2- to 4-fold less pharmacokinetic variability than Diastat^® (diazepam rectal gel) regardless of patient weight^1,13,17

Pharmacokinetic variability profiles of VALTOCO and Diastat¹⁷

AUC, area under the curve; C_max, maximum serum concentration.

90% CI

VALTOCO pharmacokinetics were not notably altered when administered during seizures vs under normal conditions¹⁰

^||In adults.

See how VALTOCO works to optimize diazepam nasal delivery

Learn how the unique formulation of VALTOCO optimizes diazepam for nasal delivery, and how it helps patients manage episodes of frequent seizure activity whenever, wherever.

VALTOCO was deemed clinically superior in administration to Diastat^®

(diazepam rectal gel) by the US Food and Drug Administration (FDA) for patients 6+ years of age¹⁸

The intranasal route of administration of VALTOCO provides a major contribution to patient care over the rectal
route of administration by providing a significantly improved ease of use.¹⁸

Because of this, the FDA has determined that VALTOCO deserves orphan drug exclusivity.¹⁸

VALTOCO was strongly preferred in a patient survey^8,#

^#Data collected from patient diaries and patient and care partner surveys of patients 6+ years of age.⁸

90% said it was “extremely easy” or “very easy” to train others to administer VALTOCO

87% felt more comfortable being treated in public with VALTOCO than with diazepam rectal gel

84% said they would prefer using VALTOCO as their seizure rescue exclusively in the future

79% were very comfortable doing activities outside the home with VALTOCO available

Improvements in seizure worry and social functioning¹⁹

PATIENTS 18+ YEARS OF AGE WITH EPILEPSY

Mean total QOLIE-31-P scores increased from day 0 (n=71) to day 365 (n=53) by 5.2 points (from 57.3 to 62.5), which also exceeded the MIC threshold of 5.19.
MIC, minimally important change; QOLIE-31-P, Quality of Life in Epilepsy—Problems.

Help your patients get to know VALTOCO

Get all the resources you need so you can educate your patients about VALTOCO.

Proven safety and tolerability with low rates of somnolence in patients 6+ years of age⁴

References

1. Valtoco. Prescribing Information. Neurelis Inc. https://www.valtoco.com/PI; 2. Data on file. REF-01245. Neurelis Inc; 3. Misra SN, Jarrar R, Stern JM, Becker DA, Carrazana E, Rabinowicz AL. Rapid rescue treatment with diazepam nasal spray leads to faster seizure cluster termination in epilepsy: an exploratory post hoc cohort analysis. Neurol Ther. 2024;13(1):221-231. doi:10.1007/s40120-023-00568-4; 4. Wheless JW, Miller I, Hogan RE, et al; DIAZ.001.05 Study Group. Final results from a Phase 3, long-term, open-label, repeat-dose safety study of diazepam nasal spray for seizure clusters in patients with epilepsy. Epilepsia. 2021;62(10):2485-2495. doi:10.1111/epi.17041; 5. Tarquinio D, Dlugos D, Wheless JW, et al. Safety of Valtoco^® (diazepam nasal spray) in children and adolescents with epilepsy: final subgroup results from a phase 3, long-term, open-label, repeat-dose safety study. Poster presented at: Child Neurology Society 50th Annual Meeting; September 29 – October 2, 2021; Boston, MA; 6. Sperling MR, Wheless JW, Hogan RE, et al; DIAZ 001.05 Study Group. Use of second doses of Valtoco^® (diazepam nasal spray) across 24 hours after the initial dose for out-of-hospital seizure clusters: results from a phase 3, open-label, repeat-dose safety study. Epilepsia. 2022;63(4):836-843. doi:10.1111/epi.17177; 7. Data on file. REF-01292. Neurelis Inc; 8. Penovich P, Wheless JW, Hogan RE, et al. Examining the patient and caregiver experience with diazepam nasal spray for seizure clusters: results from an exit survey of a phase 3, open-label, repeat-dose safety study. Epilepsy Behav. 2021;121(pt A):108013. doi:10.1016/j.yebeh.2021.108013; 9. Misra SN, Sperling MR, Rao VR, et al. Significant improvements in SEIzure interVAL (time between seizure clusters) across time in patients treated with diazepam nasal spray as intermittent rescue therapy for seizure clusters. Epilepsia. 2022;63(10):2684-2693. doi:10.1111/epi.17385; 10. Hogan RE, Tarquinio D, Sperling MR, et al. Pharmacokinetics and safety of VALTOCO (NRL-1; diazepam nasal spray) in patients with epilepsy during seizure (ictal/peri-ictal) and nonseizure (interictal) conditions: a phase 1, open-label study. Epilepsia. 2020;61(5):935-943. doi:10.1111/epi.16506; 11. Data on file. REF-01933. Neurelis Inc; 12. Agarwal SK, Kriel RL, Brundage RC, Ivaturi VD, Cloyd JC. A pilot study assessing the bioavailability and pharmacokinetics of diazepam after intranasal and intravenous administration in healthy volunteers. Epilepsy Res. 2013;105(3):362-367. doi:10.1016/j.eplepsyres.2013.02.018; 13. Tanimoto S, Koplowitz LP, Lowenthal RE, Koplowitz B, Rabinowicz AL, Carrazana E. Evaluation of pharmacokinetics and dose proportionality of diazepam after intranasal administration of NRL-1 to healthy volunteers. Clin Pharmacol Drug Dev. 2020;9(6):719-727. doi:10.1002/cpdd.767; 14. Rabinowicz AL, Carrazana E, Maggio ET. Improvement of intranasal drug delivery with Intravail^® alkylsaccharide excipient as a mucosal absorption enhancer aiding in the treatment of conditions of the central nervous system. Drugs R D. 2021;21(4):361-369. doi:10.1007/s40268-021-00360-5; 15. Milligan N, Dhillon S, Richens A, Oxley J. Rectal diazepam in the treatment of absence status: a pharmacodynamic study. J Neurol Neurosurg Psychiatry. 1981;44(10):914-917. doi:10.1136/jnnp.44.10.914; 16. Dhir A, Rogawski MA. Determination of minimal steady-state plasma level of diazepam causing seizure threshold elevation in rats. Epilepsia. 2018;59(5):935-944. doi:10.1111/epi.14069; 17. Hogan RE, Gidal BE, Koplowitz B, Koplowitz LP, Lowenthal RE, Carrazana E. Bioavailability and safety of diazepam intranasal solution compared to oral and rectal diazepam in healthy volunteers. Epilepsia. 2020;61(3):455-464. doi:10.1111/epi.16449; 18. Clinical superiority findings: 2019: Neurelis Pharmaceuticals, Inc. for Valtoco (diazepam nasal spray). US Food and Drug Administration. Accessed October 28, 2024. https://www.fda.gov/industry/designating-orphan-product-drugs-and-biological-products/clinical-superiority-findings; 19. Cramer JA, Faught E, Davis C, Misra SN, Carrazana E, Rabinowicz AL. Quality-of-life results in adults with epilepsy using diazepam nasal spray for seizure clusters from a long-term, open-label safety study. Epilepsy Behav. 2022;134:108811. doi:10.1016/j.yebeh.2022.108811

Prepare your patients to stop seizures in their tracks

Prepare your patients to stop seizures in their tracks

VALTOCO offers rapid, reliable, ready seizure treatment

A 12-month, open-label, repeat-dose safety study of patients 6+ years of age found*:

4-minute median time from VALTOCO administration to seizure cessation2,*,†

Median time to VALTOCO administration2

Median time to seizure cessation after receiving VALTOCO2

When VALTOCO was administered early, within the first 5 minutes of seizure onset, the median time to seizure cessation was 2 minutes3

87% of seizure episodes used a single dose of VALTOCO over a 24-hour period4,*

Patients with Epilepsy

Percentage of seizure episodes for which a single dose of VALTOCO was used over the course of 24 hours (N=3,853)4

Proportion of patients using single or second doses

A majority of patients returned to their usual selves within 1 hour of administration of VALTOCO8,‡

Time to return to usual self for patients after the most recent administration of VALTOCO (N=64)8

Overall mean sedation levels were low, mild, transient, and not considered clinically relevant10

Patients with Epilepsy

The number of days between treated episodes of frequent seizures nearly doubled in patients using VALTOCO over a 12-month period9

SEIVAL increased by 12.9 days over a 12-month period (n=76)9

Patients with Epilepsy

SEIVAL increased independent of concomitant medication change 9

This study represents one of the largest studies to date of treated episodes of frequent seizures11

Only VALTOCO uses Intravail® technology for rapid and reliable absorption of diazepam12,13

Nearly complete absorption of VALTOCO with 97% bioavailability relative to intravenous diazepam1,12,||

Therapeutic plasma levels of VALTOCO sustained for 24 hours 1,12

Predictable pharmacokinetics with low interpatient and intrapatient variability1,13,17,||

Pharmacokinetic variability profiles of VALTOCO and Diastat17

See how VALTOCO works to optimize diazepam nasal delivery

VALTOCO was deemed clinically superior in administration to Diastat®

(diazepam rectal gel) by the US Food and Drug Administration (FDA) for patients 6+ years of age18

VALTOCO was strongly preferred in a patient survey8,#

Improvements in seizure worry and social functioning19

PATIENTS 18+ YEARS OF AGE WITH EPILEPSY

Help your patients get to know VALTOCO

Proven safety and tolerability with low rates of somnolence in patients 6+ years of age4

Indication

IMPORTANT SAFETY INFORMATION

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

Central Nervous System (CNS) Depression

Suicidal Behavior and Ideation

Glaucoma

Neonatal Sedation and Withdrawal Syndrome

Risk of Serious Adverse Reactions in Infants due to Benzyl Alcohol Preservative

Adverse Reactions

References

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

Eligible patients

Learn how to use VALTOCO

A VALTOCO clinical study4

Primary objective

Study design

Subjects

Interventions and outcome measures

A 12-month, open-label, repeat-dose safety study of patients 6+ years of age found^*:

4-minute median time from VALTOCO administration to seizure cessation^2,*,†

Median time to VALTOCO administration²

Median time to seizure cessation after receiving VALTOCO²

When VALTOCO was administered early, within the first 5 minutes of seizure onset, the median time to seizure cessation was 2 minutes³

87% of seizure episodes used a single dose of VALTOCO over a 24-hour period^4,*

Percentage of seizure episodes for which a single dose of VALTOCO was used over the course of 24 hours (N=3,853)⁴

A majority of patients returned to their usual selves within 1 hour of administration of VALTOCO^8,‡

Time to return to usual self for patients after the most recent administration of VALTOCO (N=64)⁸

Overall mean sedation levels were low, mild, transient, and not considered clinically relevant¹⁰

The number of days between treated episodes of frequent seizures nearly doubled in patients using VALTOCO over a 12-month period⁹

SEIVAL increased by 12.9 days over a 12-month period (n=76)⁹

SEIVAL increased independent of concomitant medication change⁹

This study represents one of the largest studies to date of treated episodes of frequent seizures¹¹

Only VALTOCO uses Intravail^® technology for rapid and reliable absorption of diazepam^12,13

Nearly complete absorption of VALTOCO with 97% bioavailability relative to intravenous diazepam^1,12,||

Therapeutic plasma levels of VALTOCO sustained for 24 hours^1,12

Predictable pharmacokinetics with low interpatient and intrapatient variability^1,13,17,||

Pharmacokinetic variability profiles of VALTOCO and Diastat¹⁷

VALTOCO was deemed clinically superior in administration to Diastat^®

(diazepam rectal gel) by the US Food and Drug Administration (FDA) for patients 6+ years of age¹⁸

VALTOCO was strongly preferred in a patient survey^8,#

Improvements in seizure worry and social functioning¹⁹

Proven safety and tolerability with low rates of somnolence in patients 6+ years of age⁴

A VALTOCO clinical study⁴