The Food and Drug Administration (FDA) has issued a complete response letter (CRL) to Aquestive Therapeutics regarding the New Drug Application (NDA) for Libervant™ (diazepam buccal film) for the management of seizure clusters.

Libervant is a buccally administered soluble film of diazepam used to treat acute uncontrolled seizures in patients with refractory epilepsy on stable regimens of antiepileptic drugs (AEDs). The NDA submission included data from a randomized, open-label, 2-way crossover, phase 1/2 study that compared diazepam buccal film with Diastat rectal gel in adult patients on a stable regimen of AEDs. Patients were dosed according to a weight-based regimen. Findings from the study showed that treatment with diazepam buccal film resulted in similar systemic exposures to Diastat with significantly less variability.

However, in the CRL, the FDA noted that the study showed a lower drug exposure level than desired in certain weight groups, and cited a “small number of protocol deviations in blood draws in 1 of the studies in the NDA.” To address these concerns, the Company intends to provide additional information on pharmacokinetics modeling to the FDA to show that dose adjustments will obtain the desired exposure levels. The Company believes that it will not need to conduct any further clinical studies based on discussions with the FDA.

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“Epilepsy patients have been underserved for some time with little choice beyond device-based products such as rectally administered gels and nasal sprays and Libervant represents a meaningful and improved therapy for patients who can’t or won’t use the alternatives,” said Keith J. Kendall, President and Chief Executive Officer of Aquestive. “We look forward to quickly scheduling a meeting with the FDA to solidify Libervant’s path forward and in-turn move toward the NDA resubmission before year’s end.”

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Aquestive Therapeutics receives complete response letter from FDA for Libervant™ (diazepam) buccal film for management of seizure clusters. Accessed September 29, 2020.