LIBERVANT Buccal Film: Pioneering Pediatric Epilepsy Treatment Advancements

• LIBERVANT, a diazepam buccal formulation based on PharmFilm technology serves as a beacon of hope, offering convenient alternatives to existing device-based products, for managing acute repetitive seizure emergencies in young patients.
• LIBERVANT utilizes “fast-melt strips” for “buccal delivery of diazepam, offering promises to rewrite the narrative of acute repetitive seizure emergencies, ushering in an era of renewed optimism and therapeutic advancement.

At the 76th Annual Meeting of the American Academy of Neurology (AAN) 2024 in Denver from April 13 to 18, Aquestive Therapeutics presented an abstract for the crossover study data evaluating the effect of seizures on the absorption of their product candidate LIBERVANT (diazepam) buccal film in the treatment of epilepsy in children.

Pediatric epilepsy is a complex condition that often requires tailored treatment approaches. The current therapeutic options approved by the US FDA for refractory epilepsy in children, such as diazepam rectal gel and nasal spray, present notable challenges in terms of its convenience, discomfort, and potential social stigma associated with their administration, particularly in public settings. Consequently, there is a pressing demand for additional treatment modalities, including alternative routes of administration or novel medications, and their speed of onset to better cater to the diverse needs of pediatric epilepsy patients and enhance their treatment experience and outcomes. 

As per the study conducted, of the 24 male and female children aged 2-16 years old with refractory epilepsy received diazepam buccal film (DBF) at doses of 5.0 to 17.5 mg in the epilepsy monitoring unit setting while 17 in the interictal period and 16 in the periictal period, with 9 subjects dosed in both periods. Blood was collected over 4 hrs for analysis of diazepam plasma concentrations. Pharmacokinetic parameters were determined by noncompartmental analysis. The administration of Diazepam Buccal Film (DBF) close to a seizure resulted in a maximum plasma diazepam concentration that was similar to when DBF is dosed between seizures. This indicated that the timing of DBF administration concerning seizures did not significantly impact the achieved diazepam concentration in the bloodstream. Additionally, the speed of diazepam absorption remained consistent whether DBF was administered during or between seizures. Therefore, DBF was successful in offering a reliable and convenient method to deliver diazepam for the management of acute repetitive seizure emergencies in children, ensuring consistent drug absorption and effectiveness regardless of the timing of administration.

Furthermore, the findings demonstrated that Aquestive Therapeutic’s DBF is a novel formulation of diazepam in development that is designed to be easily administered with a more consistent, predictable pharmacokinetic profile compared with other routes of administrated diazepam in children with epilepsy. For example when it comes to the treatment of seizure clusters in children with epilepsy LIBERVANT, as an oral alternative to existing device-based products, was well-received by this patient population.

Conclusion

Addressing the unmet needs, LIBERVANT emerges as a promising solution being both a benzodiazepine known for its ability to enhance the inhibitory effects of gamma-aminobutyric acid (GABA) neurotransmission, which helps suppress abnormal brain electrical activity and its specificity designed for buccal administration, allowing for application inside the cheek with a wide, relatively immobile, and highly permeable surface area providing the stable and controlled microenvironment needed to optimize adhesion, absorption, and onset of action in children with epilepsy.