Libervant (diazepam buccal film) / Aquestive - LARVOL DELTA

Safety Profile of Diazepam Nasal Spray in Patients Aged 2–5 Years from an Ongoing, Open-label 180-day Safety Period Following Pharmacokinetic Sampling in a Phase 1/2a Study (AES 2024) - "Rationale: For pediatric patients with epilepsy aged 2 to 5 years, diazepam rectal gel has been the only immediate-use antiseizure medication approved by the US Food and Drug Administration (FDA) for the treatment of seizure clusters; diazepam buccal film was recently approved. Thirty-five patients aged 2 to 5 years were enrolled in a phase 1/2a, open-label, single-dose PK study of diazepam nasal spray with a 180-day open-label safety period. In this ongoing study, 88.6% of patients completed the safety period. Treatment-related TEAEs were reported in 20.0% of patients, none of which were serious."

Clinical • P1/2 data • PK/PD data • CNS Disorders • Depression • Epilepsy • Pediatrics • Psychiatry

Aquestive Therapeutics Receives U.S. FDA Approval and Market Access for Libervant (diazepam) Buccal Film in Pediatric Patients Ages 2 to 5 and Provides Update on Anaphylm (epinephrine) Sublingual Film (GlobeNewswire) - "Aquestive Therapeutics, Inc...announced the U.S. Food and Drug Administration (FDA) has approved Libervant (diazepam) Buccal Film for the acute treatment of intermittent, stereotypic episodes of frequent seizure activity (i.e., seizure clusters, acute repetitive seizures) that are distinct from a patient’s usual seizure pattern in patients with epilepsy between 2 to 5 years of age....The Company is currently in the clinic completing the remaining studies required for the submission of the New Drug Application (NDA) for Anaphylm, which is planned for the end of 2024. The Company will provide a more detailed update on Anaphylm at its upcoming first quarter 2024 earnings call on May 8, 2024."

NDA • CNS Disorders • Epilepsy

Crossover Study Evaluating the Effect of Seizures on the Absorption of Diazepam from a Buccal Film Formulation in Children with Epilepsy (AAN 2024) - "Objective:To compare plasma exposures from diazepam buccal film (DBF) administered in children with epilepsy under periictal or interictal conditions.Background:Diazepam buccal film (DBF) is a novel diazepam dosage form for treating acute repetitive seizures. Even if DBF is administered in close proximity to a seizure, the maximum plasm diazepam concentration achieved is comparable to that observed when DBF is dosed in between seizures. Likewise, the speed of diazepam absorption is not affected by dosing DBF either during or between seizures. DBF provides a convenient way to deliver diazepam for the treatment of acute repetitive seizure emergencies in children."

Clinical • CNS Disorders • Epilepsy

Aquestive Therapeutics Receives FDA Acceptance of New Drug Application (NDA) for Libervant (diazepam) Buccal Film in Pediatric Patients and Assignment of Prescription Drug User Fee Act (PDUFA) Date (GlobeNewswire) - "Aquestive Therapeutics, Inc...today announced acceptance by the U.S. Food and Drug Administration (FDA) of the Company’s NDA for Libervant™ (diazepam) Buccal Film in pediatric patients between two and five years of age and the assignment of a PDUFA goal date of April 28, 2024....Aquestive’s NDA for approval of Libervant™ (diazepam) Buccal Film for the acute treatment of intermittent, stereotypic episodes of frequent seizure activity (i.e., seizure clusters, acute repetitive seizures) in patients between two and five years of age has been accepted by the FDA."

NDA • PDUFA date • CNS Disorders • Epilepsy

Aquestive Therapeutics Provides Business Update and Announces Chief Medical Officer Appointment (GlobeNewswire) - "Aquestive Therapeutics, Inc...today provided an update on recent business developments and announced the appointment of Carl N. Kraus, M.D. as Chief Medical Officer of the Company...Aquestive submitted a New Drug Application (NDA) to the U.S. Food and Drug Administration (FDA) for approval of Libervant™ (diazepam) Buccal Film for the acute treatment of intermittent, stereotypic episodes of frequent seizure activity (i.e., seizure clusters, acute repetitive seizures) in patients between two and five years of age....The Company expects to hear from the FDA on the acceptance of, and issuance of a target action date on, this pediatric NDA within approximately two months."

NDA • CNS Disorders • Epilepsy

Aquestive Therapeutics Announces Publication of Crossover Food Effect Study of Diazepam Nasal Spray in Epilepsia (Yahoo Finance) - P1 | N=24 | "Aquestive Therapeutics, Inc...announced today the publication of a crossover food effect pharmacokinetic study of diazepam nasal spray in the peer-reviewed scientific journal Epilepsia....It was included by Aquestive as part of its New Drug Application (NDA) for Libervant™ (diazepam) Buccal Film that was submitted to the U.S. Food & Drug Administration (FDA)....Under fed conditions, the mean maximum plasma diazepam concentration was decreased by 48% (P <0.0001) and the overall diazepam exposure during the first four hours was reduced by 57% (P <0.0001) compared with fasted conditions. The time to maximum plasma concentration was 4.0 hours in the fed state, compared with 2.0 hours in the fasted state (P <0.0001)."

P1 data • CNS Disorders • Epilepsy

Aquestive Therapeutics Enters License and Supply Agreement with Pharmanovia for Libervant (diazepam) Buccal Film for European and MENA Markets (GlobeNewswire) - "Aquestive Therapeutics, Inc...announced it has entered a license, and supply agreement for Libervant™ (diazepam) Buccal Film with Pharmanovia, a global lifecycle management healthcare company, for treatment of prolonged or acute, convulsive seizures in all ages, across the European Union, United Kingdom, Switzerland, and Norway, as well as countries in the Middle East and North Africa (MENA)."

Licensing / partnership • CNS Disorders • Epilepsy

"$AQST Aquestive Therapeutics Receives FDA Tentative Approval for Libervant™ (diazepam) Buccal Film https://t.co/Q6ptH9UwZx" (@stock_titan)

FDA event

Aquestive Therapeutics Reports Second Quarter 2022 Financial Results and Provides Business Update (GlobeNewswire) - "Aquestive continues to interact with the United States Food and Drug Administration (FDA) regarding the orphan drug review of the New Drug Application (NDA) for Libervant after receiving a notification from the FDA indicating that the Agency would not be ready to act by the PDUFA target goal date of December 23, 2021 for the Company’s NDA for Libervant."

PDUFA date • CNS Disorders • Epilepsy

Aquestive Therapeutics Receives Notification from FDA that It Will Not Be Ready to Take Action by December 23, 2021 for the Company’s NDA for Libervant (diazepam) Buccal Film (GlobeNewswire) - "Aquestive Therapeutics, Inc...announced today that, regarding the review of the New Drug Application (NDA) for Libervant™ (diazepam) Buccal Film for the treatment of breakthrough seizures and seizure clusters, the U.S. Food & Drug Administration (FDA) sent the following notice to the Company;...'the Agency is still considering the regulatory issues related to the approvability of Libervant, and will not be ready to take an action by December 23, 2021. No additional information is needed from you at this time. We are currently unable to provide an estimate of the timing of an expected action; however, we will provide any updates we can as they are available'"

PDUFA date • CNS Disorders • Epilepsy

Diazepam Buccal Film (DBF): Final Results from a Phase 3, Open-Label, Safety and Tolerability Study of Chronic Intermittent Use in Pediatric, Adolescent and Adult Subjects with Epilepsy (AES 2021) - "These observations show DBF is a safe, well-tolerated, and usable treatment for chronic intermittent use as a rescue medication for patients with epilepsy (2 to 62 years of age)."

Clinical • P3 data • CNS Disorders • Epilepsy • Fatigue • Pediatrics

Safety of Diazepam Buccal Film in Children with Epilepsy: Subgroup Results from a Phase 3, Open-Label, Safety and Tolerability Study (AES 2021) - "In this sub-analysis of a long-term safety study, the safety profile of Diazepam Buccal Film was similar between all age groups."

Clinical • P3 data • CNS Disorders • Epilepsy • Pediatrics

Burden of Seizure Clusters on Patients with Epilepsy: Survey of Patient Perspectives and Preference (AES 2021) - "With the recent advancement of the Diazepam buccal film (DBF), patients have more hope and freedom through increased autonomy for managing their seizure clusters... This survey results strongly confirm the need for highly portable rescue medications, in proximity, with the potential for self-administration where and when they are needed. These survey results substantiate the significant contribution to patient care that DBF offers."

Clinical • CNS Disorders • Epilepsy

Aquestive Therapeutics Negotiates Six Month Extension to June 30, 2022 for Additional Libervant Related Capital Under Current Debt Agreement (BioSpace) - "Aquestive Therapeutics (Formerly known as MonoSolRx) Inc...announced today that it has reached an agreement with its lenders to amend the base indenture providing an extension of the term by six months to June 30, 2022 to provide additional debt in the aggregate of up to $30.0 million. In line with the extension to June 30, 2022, Aquestive is entitled, at its option, to draw up to $10 million following FDA approval for Libervant, the first orally delivered diazepam product for the management of seizure clusters, and up to an additional $20 million following the FDA grant of U.S. market access for Libervant."

Financing • CNS Disorders • Epilepsy

Aquestive Therapeutics Announces FDA Acceptance of New Drug Application (NDA) Resubmission for Libervant (diazepam) Buccal Film (GlobeNewswire) - "Aquestive Therapeutics, Inc...announced today that the U.S. Food and Drug Administration (FDA) has accepted for filing the resubmission of the New Drug Application (NDA) for Libervant™ (diazepam) Buccal Film for the management of seizure clusters. The FDA has assigned a Prescription Drug User Fee Act ('PDUFA') target goal date of December 23, 2021....'We are preparing for the commercial launch of Libervant, if approved for U.S. market access, in the first half of 2022...'"

Launch US • PDUFA date • sNDA • CNS Disorders • Epilepsy

Aquestive Therapeutics Resubmits New Drug Application for Libervant (diazepam) Buccal Film (GlobeNewswire) - "Aquestive Therapeutics, Inc...announced today the resubmission of its New Drug Application (NDA) to the U.S. Food and Drug Administration (FDA) for Libervant™ (diazepam) Buccal Film for the management of seizure clusters in response to the September 25, 2020 Complete Response Letter (CRL) from the FDA...The Company anticipates a six-month review process and expects to receive a PDUFA goal date in late 2021."

PDUFA date • sNDA • CNS Disorders • Epilepsy

Pharmacokinetics and Safety Study of Diazepam Buccal Film (DBF) in Pediatric Subjects With Epilepsy (clinicaltrials.gov) - P2; N=24; Completed; Sponsor: Aquestive Therapeutics; Active, not recruiting ➔ Completed; N=18 ➔ 24

Clinical • Enrollment change • Trial completion • CNS Disorders • Epilepsy • Pediatrics

Aquestive Therapeutics Reaffirms Near-Term NDA Resubmission for Libervant (diazepam) Buccal Film Following FDA Feedback (GlobeNewswire) - "Aquestive Therapeutics, Inc....today announced that the Food and Drug Administration (FDA) has provided further guidance to Aquestive regarding the information to be included in the New Drug Application (NDA) for Libervant™ (diazepam) Buccal Film for the management of seizure clusters. The further guidance from the FDA addresses the revised weight-based dosing regimen, modeling and simulations data that Aquestive provided to the Agency in December 2020....'We have a clear path to resubmitting our NDA for Libervant and expect to do so around the end of the second quarter of 2021.'...Once resubmitted, Aquestive anticipates a six month review process."

FDA event • CNS Disorders • Epilepsy

"$AQST Aquestive Therapeutics Reaffirms Near-Term NDA Resubmission for Libervant™ (diazepam) Buccal Film Following FDA Feedback https://t.co/SGGIzyVI46" (@stock_titan)

FDA event • NDA

"$AQST Aquestive Therapeutics Completes FDA Type A Meeting on Libervant https://t.co/wSPsE8NDyL" (@stock_titan)

Safety and tolerability associated with chronic intermittent use of diazepam buccal film in adult, adolescent, and pediatric patients with epilepsy. (PubMed, Epilepsia) - "In this observational study of chronic intermittent use, DBF was easy to administer, safe, and well tolerated in adult, adolescent, and pediatric patients with epilepsy experiencing seizure emergencies. DBF can be readily self-administered by adults with epilepsy, as well as successfully administered by a caregiver in seizure emergencies."

Clinical • Journal • CNS Disorders • Epilepsy • Oncology • Pediatrics

Safety and Tolerability Study of Diazepam Buccal Soluble Film (DBSF) in Subjects With Epilepsy (clinicaltrials.gov) - P3; N=148; Completed; Sponsor: Aquestive Therapeutics; Active, not recruiting ➔ Completed; Trial completion date: Nov 2020 ➔ Jun 2020

Trial completion • Trial completion date • CNS Disorders • Epilepsy • Pediatrics

Diazepam buccal film for the treatment of acute seizures. (PubMed, Epilepsy Behav) - "In a crossover comparative study with diazepam rectal gel (Diastat®) in adult patients with epilepsy, DBF performed equivalently to the rectal gel, but peak exposures were less variable. Diazepam buccal film is a convenient alternative for out-of-hospital treatment of seizure exacerbations. Proceedings of the 7th London-Innsbruck Colloquium on Status Epilepticus and Acute Seizures."

Journal • Review • CNS Disorders • Epilepsy

"yes - and another #pdufa is coming to $AQST on September 27 (Libervant - AQST-203)" (@keitrader)

PDUFA date

Safety and Tolerability Study of Diazepam Buccal Soluble Film (DBSF) in Subjects With Epilepsy (clinicaltrials.gov) - P3; N=148; Active, not recruiting; Sponsor: Aquestive Therapeutics; Recruiting ➔ Active, not recruiting; Trial completion date: Apr 2020 ➔ Nov 2020; Trial primary completion date: May 2019 ➔ Oct 2020

Clinical • Enrollment closed • Trial completion date • Trial primary completion date