VALTOCO (Diazepam Nasal Spray) For Seizure Cluster Rescue

• VALTOCO, a nasal spray formulation of diazepam, offers enhanced convenience and simplicity for managing seizure clusters, effectively meeting a crucial gap in epilepsy care. This attribute not only empowers individuals to manage their treatment autonomously but also offers reassurance and assistance to caregivers during crucial moments of intervention.
• VALTOCO represents an exclusive formulation of diazepam, leveraging the innovative Intravail transmucosal absorption technology, distinguishing it as a dependable, secure, and easily accessible solution tailored to address the challenges associated with seizure clusters.

Delivering medication during a seizure often poses hurdles, from social stigma to logistical obstacles, particularly in public environments. Moreover, the diverse frequency and intensity of seizure clusters among individuals emphasize the necessity for personalized treatment approaches to fulfill these unmet requirements. Yet, Neurelis’s VALTOCO stands apart, offering a discreet and convenient nasal spray format that accommodates both patients and caregivers with its compactness and intuitive design. These distinctive attributes were vividly showcased in their poster display, spotlighting the product’s portability and user-centric features. 

At the 76th annual meeting of the American Academy of Neurology (AAN) 2024, held in Denver from April 13 to 18, Neurelis presented two posters on VALTOCO (diazepam nasal spray) for the treatment of episodes of frequent seizure activity (i.e., seizure clusters) in patients with epilepsy ages 6 to 65 years, describing the time to treatment across different subpopulations, and providing insights into the characterization of a repeat-dosing model for preclinical diazepam studies.

Diazepam nasal spray is approved for the acute treatment of seizure clusters in patients with epilepsy aged ≥ 6 years. A novel preclinical repeat-dosing study of diazepam (DZP) in a rat model was conducted to evaluate potential dosing strategies for preclinical in-life efficacy studies. Repeat dosing of DZP (0.75–3 mg/kg) resulted in a dose-dependent increase in plasma and brain DZP levels up to 6 hours. In this rat model, a repeat-dosing paradigm of DZP ≤3 mg/kg resulted in sustained DZP levels in plasma and brain. Accumulation of DZP in rat brain vs plasma suggests that DZP may be long-acting at the site of action. This repeat-dosing paradigm for DZP in rats mimics plasma drug concentrations seen in humans, offering a preclinical tool to study the impact of benzodiazepine rescue therapy on seizure-cluster biology. 

The second poster presented a post hoc analysis of a long-term safety study on DZP nasal spray, revealing that quicker administration correlated with expedited resolution of seizure clusters. Out of 4466 observations from 163 patients, 3225 were analyzed, demonstrating that shorter time (<5 min) to treatment was consistently linked to faster seizure cluster termination across various age groups and treatment scenarios. This underscores the importance of prompt seizure recognition and treatment in mitigating injury risk and healthcare utilization.

The findings underscored that VALTOCO formulation and route of administration hold promise due to their ease of use, high bioavailability, favorable safety profile, and social acceptability. Nasal administration of diazepam not only provides a vital treatment avenue but also empowers non-medical caregivers, such as family members or school personnel, to effectively manage seizure clusters. This approach aims to mitigate seizure cluster episodes and reduce the necessity for emergency department visits, ultimately enhancing the quality of life for individuals grappling with drug-resistant epilepsy. Furthermore, diazepam nasal spray achieves comparable exposure levels when compared with rectal diazepam, emphasizing its efficacy and reliability as a treatment option.

Conclusion: Neurelis’ analysis illuminates VALTOCO’s transformative potential in managing seizure clusters across a wide age range in epilepsy patients. Demonstrating sustained DZP levels in plasma and the brain, akin to human physiology, suggests enduring therapeutic benefits. The escalating DZP accumulation in the brain with repeated dosing, as indicated by brain-to-plasma ratios, underscores the suitability of this dosing regimen for preclinical efficacy studies. This breakthrough holds promise for advancing seizure management and improving treatment outcomes for epilepsy patients.