At the end of the 12-month treatment period, interseizure cluster intervals increased from 14.8 days in the first period to 35.8 days in the final 90-day stretch.
Results from an exploratory analysis of a 12-month study demonstrated that treatment with diazepam nasal spray (Valtoco; Neurelis) significantly increased the time between interseizure cluster intervals (ISCIs), which may reflect a salutary effect of cluster treatment.1,2
From period 1 to period 4, the mean ISCIs for the 76-patient cohort increased significantly, from 12.2 days to 25.7 days (P <.01). Presented at the 2nd North American Epilepsy Congress, held virtually May 5-8, 2022, the study investigators concluded that these findings "raise the possibility that intermittent treatment alters the underlying biology of clusters, which should be evaluated in further studies."2
The phase 3 open-label, repeat-dose study included 163 patients with seizure clusters (SCs), aged 6 to 65 years, who received at least 1 dose of diazepam nasal spray. ISCIs were evaluated using 90-day periods for patients treated with at least 2 doses across period 1 and the following 3 periods. Of 151 patients with ISCI data, 120 had data in period 1 and another period, while 76 individuals had at least 1 ISCI in periods 1 to 4, or across the 1-year stretch.
In the 120-patient cohort, ISCIs increased from 14.8 days in period 1 (0-90 days; n = 120) to 35.8 days in period 4 (271-360 days; n = 87), which was statistically significant (P <.001). No effects of age, treatment duration, change in concomitant medications, or quality of life were observed.2
"Valtoco and other rescue therapies play a critical role in treatment plans for people with poorly controlled epilepsy and seizure clusters," study investigator Adrian Rabinowicz, MD, senior vice president, Clinical Development and Medical Affairs, Neurelis, said in a statement.1 “These latest SEIVAL (SEIzure InterVAL) results lend themselves to a hypothesis that intermittent treatment should be further studied to investigate potential biological and behavioral changes that may impact the natural course of seizure clusters."
The long-term safety of diazepam was evaluated in a separate analysis using the same cohort of patients. Here, patients received 5- to 20-mg doses of diazepam based on age (≤11 years and ≥12 years, respectively) and weight, with second doses administered 4 to 12 hours later if needed. Among the 163 treated patients (6-11 years: 27.6%; ≥12 years: 72.4%), 77.8% (35 of 45) of patients aged 6 to 11 years and 83.1% (98 of 118) of patients aged at least 12 years were exposure to treatment for at least 12 months.3
In total, the 6 to 11 years age group had 784 SCs and 90 (11.5%) individuals used a second dose. Of those, 22 patients administered their second dose within 4 hours of their first, 7 between 4 to 6 hours after, 22 between 6 to 12 hours, and 39 between 12 to 24 hours. For the older group, 3069 SCs were recorded, with 395 (12.9%) needing second doses. Similarly, the timing of the second medication varied, with 130 individuals administering diazepam within 4 hours, 65 within 4 to 6 hours, 234 within 6 to 12 hours, and 105 in 12 to 24 hours.
The safety profile of intranasal diazepam was consistent with the rectal form of the medication, with no serious treatment-emergent adverse events (TEAEs) considered treatment related. TEAEs occurred in 91.1% of patients in the 6 to 11 years age group, 40% of which were serious, and 6.7% considered treatment related. For those older than 12 years, 78.8% experienced TEAEs; 27.1% were serious, and 22.9% were considered treatment related. Notably, there was 1 death in the study, but it was not treatment related. Between the 2 groups, the retention rates until study closure were 75.5% and 76.3%, respectively.
"We continue to explore the robust data set generated by the VALTOCO phase 3 study in people with uncontrolled epilepsy that experience episodes of frequent seizure activity," study investigator Sunita Misra, MD, senior medical director, Neurelis, said in a statement.1 "This data has the potential of evolving the landscape of care for epilepsy patients in the future and we are incredibly encouraged by the exploratory analysis generated thus far."