Abstracts

Rationale: NRL-1 (Valtoco™) is a diazepam nasal spray formulated with Intravail® A3 for use in patients with epilepsy who experience seizure emergencies despite stable regimens of antiepileptic drugs (AEDs). It is clinically relevant to understand how treatment with NRL-1 may be affected by concomitant use of AEDs, especially another benzodiazepine like clobazam, which is indicated for seizures associated with Lennox-Gastaut syndrome, a severe form of epilepsy that is refractory to most AEDs. Methods: Patients were adults and children/adolescents with epilepsy having seizures despite a stable regimen of AEDs. All patients or their legal representative provided written informed consent. Patients/caregivers were trained in the use of the intranasal sprayer for NRL-1 administration. During patient follow-up of up to 1 year, NRL-1 was administered at 5, 10, 15, or 20 mg based on weight, with a second dose administered as needed 4 to 12 hours later; doses could be adjusted by the investigator for efficacy or safety. This analysis descriptively evaluated NRL-1 utilization and safety profile in patients concomitantly using clobazam relative to the non-clobazam patient subgroup. Results: A total of 132 patients were enrolled and administered NRL-1 (aged 6 to 65 years; 53.8% female; 82.6% white). Among these patients, 32 (24.2%) were using clobazam as part of their AED regimen; these patients were younger than the non-clobazam subgroup (Table 1). Although duration of NRL-1 exposure was longer in the non-clobazam subgroup, a higher proportion of patients in the clobazam subgroup were considered “super users” with ≥2 doses/month on average (68.8% vs 55.0%) (Table 1). Effectiveness, reflected as the percentage of seizure episodes that responded to a single dose of NRL-1 was similar for both groups (93.1% for the clobazam subgroup and 91.0% for the non-clobazam subgroup). The proportions of patients with treatment-emergent adverse events (TEAEs) were similar in the clobazam (78.1%) and non-clobazam (66.0%) subgroups, as were the proportions with treatment-related TEAEs (Table 2). Serious TEAEs were higher among the clobazam patients (46.9% vs 22.0%), but none of the serious TEAEs was deemed related to treatment. The most common TEAEs generally had a higher incidence in the clobazam subgroup (Table 2), especially those events related to the central nervous system, such as seizures (21.9% vs 10.0%) and status epilepticus (6.2% vs 1.0%). Conclusions: Results from this long-term study suggest that use of NRL-1 is possible in patients concomitantly using clobazam as part of their AED regimen. The effectiveness of NRL-1 was not affected by concomitant clobazam use, and there appeared to be minimum effect on safety/tolerability. Even in “super users”, a reflection of more refractory patients, the safety profile was not affected. Funding: Neurelis, Inc.