Aculys Reports Positive Phase 3 Findings of Diazepam Nasal Spray in Epilepsy

Kazunari Tsunaba

Recently announced interim findings from a Japanese-based phase 3 study assessing Aculys Pharma’s diazepam nasal spray showed that the antiseizure medication was effective across multiple clinical end points, demonstrating efficacy and safety. Based on these data, the company plans to intend to submit a new drug application in Japan for the agent as a treatment for patients with recurrent epileptic seizures.¹

According to the company, treatment with a single dose of the agent resulted in resolution of clinically relevant seizures within 10 minutes after administration. In addition, diazepam-treated participants remained free from seizures or convulsions for 30 minutes after starting treatment. Although there were no specifics on the data released, the company plans to present the results of the interim analysis at an upcoming Japanese medical conference.

"Many epilepsy patients are able to lead normal social lives with appropriate treatment, but those who have difficulty controlling their seizures with medication are living with the anxiety of seizures that could occur anywhere and at any time," Kazunari Tsunaba, president and representative director, Aculys Pharma, said in a statement.¹ "We believe that access to emergency treatment that is convenient and easy for non-medical personnel to use appropriately in the event of a seizure, in addition to being effective and safe, will help reduce the emotional burden on patients and their caregivers, as well as the risk of sequelae due to prolonged seizures."

The study, the first such phase 3 study of diazepam nasal spray in Japan, assessed Aculy’s formulation of the antiseizure medication for which has been FDA-approved since 2020.² At the conclusion of the treatment period, treatment with the therapy resulted in benefits on efficacy end points, as well as no serious AEs and no AEs related to respiratory depression.

Aculys Phara currently holds an executive license to develop and commercialize the diazepam nasal spray in Japan and the Asia-Pacific region. The therapy, originally developed by Neurelis and marketed under the name Valtoco, was approved as the first nasal spray to be used as a rescue treatment for patients with epilepsy aged 6 and older. Findings from an open-label, repeat dose, clinical trial of over 130 patients and more than 2000 seizures served as the basis for the drug’s approval.

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Tsunaba added, "Intranasal anticonvulsants, which are easy for families and caregivers to administer to patients with epileptic seizures, have been approved in the U.S. since 2020 and are widely used there. In our efforts to eliminate the problems of drug lag and drug loss, we will continue to work with medical professionals and regulatory authorities to promote our business in order to bring innovative treatments and hope to patients with recurrent seizures and their caregivers as soon as possible."¹

In late 2022, post-hoc data from the study supporting Valtoco’s approval further demonstrated diazepam’s impact on prolonging time intervals between seizure clusters. In an exploratory analysis of 151 patients who had 1 ore more seizure interval (SEIVAL), median SEIVALS increased significantly from Periods 2 to 4 (Period 1: day 0; Period 4: day 360) compared with Period 1 (P <.01). Additionally, SEIVAL increased from 12.2 days in Period 1 to 25.7 days in Period 4.³

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).

REFERENCES
1. Aculys Pharma delivers positive phase 3 clinical study interim analysis result of a diazepam nasal spray: an antiepileptic drug for the treatment of epileptic seizures. News release. Aculys Pharma. October 18, 2023. Accessed October 22, 2023. https://www.prnewswire.com/news-releases/aculys-pharma-delivers-positive-phase-3-clinical-study-interim-analysis-result-of-a-diazepam-nasal-spray-an-antiepileptic-drug-for-the-treatment-of-epileptic-seizures-301959812.html
2. Neurelis announces FDA approval for seizure rescue treatment Valtoco (diazepam nasal spray) that incorporates the science of intraVail for consistent and reliable absorportion. News release. January 13, 2020. Accessed October 22, 2023. https://neurelis.com/neurelis-news/neurelis-announces-fda-approval-seizure-rescue-treatment-valtocor-diazepam-nasal-spray-incorporates
3. Misra SN, Sperling MR, Rao V, et al. Significant improvements in SEIzure interVAL (time between seizure clusters) across time in patients treated with diazepam nasal spray as intermittent rescue therapy for seizure clusters. Epilepsia. Published August 5, 2022. doi:10.1111/epi.17385