The safety profile of diazepam remained similar to what was previously observed, but generally, more patients in the concomitant benzodiazepine subgroup experienced more TEAEs.
Interim data from a long-term phase 3 study of diazepam nasal spray (Valtoco; Neurelis) demonstrated that the treatment remains effective in reducing the percentage of seizures regardless of whether patients concomitantly use other benzodiazepines as part of their daily antiseizure drug (ASD) regimen.1
The results were presented virtually at the American Epilepsy Society (AES) Annual Meeting, December 4–8, 2020, by Eric Segal, MD, director of pediatric epilepsy, HMH Hackensack University Medical Center.
Segal and colleagues found that the percentage of seizure episodes using a single dose of diazepam nasal spray was similar for those with concomitant benzodiazepines (90.5%) compared to those without (92.4%).
Segal told NeurologyLive, “The take home message is that there doesn’t appear to be a significant tolerance to benzodiazepines at the prescribed doses emergently. And second, we don’t see any increased side effects in that population.”
In total, 158 patients received diazepam nasal spray (aged 6 to 65 years; 53.8% female; 82.3% white), with 119 (75.3%) of those using concomitant benzodiazepines as part of their ASD regimen and 39 (24.7%) who were not.
The study’s length helped further improve the results, with most patients in both groups using the spray for ≥12 months (with concomitant benzodiazepines, 90 [75.6%]; without, 26 [66.7%]). Exposure to ≥2 doses of diazepam nasal spray was recorded in 70 patients (58.8%) with concomitant benzodiazepines and in 19 patients (48.7%) who took the treatment by itself.
The study authors noted, “in most cases, the number of doses used for seizure activity was independent of the presence of concomitant benzodiazepines, and no difference in retention rate was seen.”
Treatment with diazepam nasal spray also showed a similar safety profile to what had been previously observed. The proportion of patients who experienced treatment-emergent adverse events (TEAEs) were higher for those with concomitant benzodiazepines (79.8%) than those without (61.5%).
There was also a higher proportion of patients using concomitant benzodiazepines that experienced serious TEAEs (30.3%) compared to those just on the diazepam nasal spray (23.1%).
Seizure, pyrexia, and nasopharyngitis, the most common TEAEs observed, had a generally higher incidence in the concomitant benzodiazepines subgroup. Notably, retention rate was 84.1% for those with concomitant benzodiazepines and 76.9% for those without.
"The end goal with this data is to show real world experience using a medication that’s relatively new. Clinicians can see that this is not just a drug that has a honeymoon effect, but a medication that has real staying power and persistence,” Segal added.
The FDA approved intranasal diazepam for the treatment of acute, intermittent, stereotypic episodes of frequent seizure activity, otherwise known as seizure clusters or acute repetitive seizures in January 2020. The drug, which is a Schedule IV controlled substance, became the first intranasal rescue formulation approved for patients age 6 and older. Notably, the FDA granted the drug 7 years of Orphan Drug Exclusivity.2
For more coverage of AES 2020, click here.