A doubling of mean seizure intervals was demonstrated from period 1 to period 4 for the 76-patient cohort who received the Neurelis nasal spray treatment across 360 days.
According to newly published data, treatment with diazepam nasal spray (Valtoco; Neurelis), an FDA-approved antiseizure medication, resulted in significant prolongation of time intervals between seizure clusters in patients with epilepsy. The full findings, published in Epilepsia, follow exploratory analysis presented at the Second North American Epilepsy Congress, held virtually on May 5-8, 2022.1,2
The results were from a phase 3, open-label, repeat-dose safety study conducted from April 2016 to July 2020. Among a cohort of 163 treated patients, 151 had 1 or more seizure interval (SEIVAL; time between seizure clusters). For those who received consistent treatment from Period 1 (day 0) to Period 4 (day 360) the mean number of seizure clusters treated was 9.0 in Period 1, 7.9 in Period 2, 8.4 in Period 3, and 6.6 in Period 4. Similarly, median SEIVALS increased significantly from Periods 2 to 4 compared with Period 1 (P <.01). Additionally, SEIVAL increased from 12.2 days in Period 1 to 25.7 days in Period 4.
"The most exciting finding of the study is the robustness of the signal in the cluster-interval data," coinvestigator Jurriaan Peters, MD, PhD, assistant professor of neurology, Harvard Medical School, said in a statement.1 "The results consistently showed a clinical and statistical increase in the time between use of intranasal diazepam, Valtoco, over time. This data highlights the potential for future research into additional benefits of rescue medications in treating individual seizure clusters."
The same consistent pattern of increased SEIVAL was found when investigators eliminated retreatments, with increases from 13.9 days in Period 1 to 26.8 days in Period 4. This ensured measurements between seizure clusters by eliminating second doses of diazepam nasal spray for a single cluster within 24 hours of the first dose. Similar increases across time were seen for the consistent cohorts for Periods 1 to 5 (n = 41) and Periods 1 to 6 (n = 26), which included patients who opted for treatment for more than the original 12-month period.
In terms of duration of exposure to diazepam nasal spray, the mean change in SEIVAL was similar among those with exposure of less than 12 months (mean change, 28.3 days; n = 6) compared with the larger group who were exposed for more than a year (mean change, 21.4 days; n = 81). When a subgroup of patients with changes in concomitant daily medications (n = 56) was compared with a subgroup without such changes (n = 20), no between-group differences were seen in mean change of SEIVAL across Periods 2 to 4.
"Neurelis is deeply committed to improving the lives of people with epilepsy and we are particularly enthusiastic about the potential of these findings," Craig Chambliss, chief executive officer, Neurelis, said in a statement.1 "Until now, no data existed on the impact of intermittent rescue therapy on the long-term course of seizure clusters, and these results may open important new avenues of research on timely, safe, and effective acute treatment application."
SEIVALs were also calculated for adult patients who completed the Quality of Life in Epilepsy (QOLIE)-31-P tool, an epilepsy-specific instrument that uses numeric values (1-100) assigned to responses, with higher scores indicating better quality of life. Among this subgroup (n = 74) of responders, findings showed that quality-of-life scores were maintained across the 12-month study period, generally with small directional improvement in mean overall scores. From Periods 1 to 4 in the consistent cohort, the subgroup of adults who completed the QOLIE-31-P at both baseline and day 365 had similar change in SEIVAL between Period 1 and Period 4 (12.2 days) to the total consistent cohort (12.9 days; n = 76).
For all patients with QOLIE-31-P data and those in the consistent cohort with QOLIE-31-P data, investigators found similar differences in scores from day 0 to day 365 on Seizure Worry (8.7 and 6.4 points, respectively) and Social Functioning (8.1 and 7.7 days, respectively), 2 subscales of the QOLIE-31-P. Minimally important change, defined as 7.4 for the Seizure Worry subscale and 4.0 for the Social Functioning subscale, was shown for all patients with available data on both subscales and for the SEIVAL consistent cohort group on the Social Functioning subscale.