Aquestive Therapeutics Receives FDA Tentative Approval for Libervant™ (diazepam) Buccal Film

Aquestive Therapeutics, Inc. | August 31, 2022 | Read time : 05:00 min

Aquestive Therapeutics
Aquestive Therapeutics, Inc. a pharmaceutical company advancing medicines to solve patients' problems with current standards of care and provide transformative products to improve their lives, announced today that the U.S. Food & Drug Administration has granted tentative approval for Libervant™ Buccal Film for the acute treatment of intermittent, stereotypic episodes of frequent seizure activity that are distinct from a patient’s usual seizure pattern in patients with epilepsy 12 years of age and older.

"Tentative approval" means the FDA has concluded that Libervant has met all required quality, safety, and efficacy standards for approval but, due to an existing FDA regulatory grant of orphan drug market exclusivity for Valtoco®, a diazepam nasal spray product, Libervant is not yet eligible for marketing in the United States. As a result of the FDA determination, the Agency cannot give final approval for Libervant until the expiration or inapplicability of the orphan drug market exclusivity, including, for example, by court order, a selective waiver of the orphan drug exclusivity, or a reversal of the FDA’s decision and determination that Libervant is “clinically superior” to Valtoco.

The FDA’s decision provides welcome clarity to our business. The tentative approval of Libervant is a significant achievement that brings us one step closer to bringing this important medicine to patients who are unable or choose not to use the current standards of care. Libervant has the potential to offer these patients a treatment option that is simple, portable, and precise. A significant unmet need exists for additional alternate delivery options given the ongoing shortage of diazepam rectal gel, which continues to represent a substantial portion of the current diazepam rescue market. This FDA action further validates our ability to gain FDA approval of our pipeline programs. We look forward to continuing the rapid progression of AQST-109 for the treatment of severe allergic reactions, including anaphylaxis, towards a filing with the FDA.”

Daniel Barber, Chief Executive Officer of Aquestive

“We continue to examine the FDA’s determination on Libervant market access and plan to request a meeting with the Agency as soon as possible. We disagree with the FDA’s determination on the various points presented by the Agency and believe that, particularly in the case of our submitted studies on the effect of food on the absorption of diazepam formulations, Libervant has the distinct advantage of being able to be readily administered when needed without regard to food, providing an important benefit to patients. This is important to patients as rapid and extensive drug absorption is critical in a rescue situation. We will continue to vigorously engage with the FDA on the need for these data to be carefully considered.”

During the review process, the Company submitted to the FDA the results of a 2021 Aquestive sponsored randomized, open-label, two-sequence, two-period, two-treatment crossover study to evaluate the effect of food on the pharmacokinetics of Valtoco in healthy adult subjects. The results of this study indicated that, when Valtoco is administered after a high fat meal, the maximum drug concentration (Cmax) was reduced by 48% compared to Valtoco administered to subjects in a fasted state. The study also showed that the time to maximum drug concentration (Tmax) of Valtoco doubled from 2 hours to 4 hours when administered after a high fat meal. Aquestive provided the data along with a cross-study comparison to a similar study performed with Libervant, to FDA during the review process.

The FDA’s decision concluded that the information Aquestive submitted was not sufficient to overturn the Agency's previous conclusion regarding the lack of food effect for Valtoco. Specifically, the FDA stated that “[a] cross-study comparison is not considered [by the reviewer] to be a suitable approach for making a quantitative comparison of plasma concentrations between different products because of the lack of a common reference standard between the two studies.” Aquestive will seek to gain alignment with the Agency on a reasonable path to appropriately characterize the food effect of Valtoco including potentially conducting a comparative study as indicated by the FDA.

About Libervant
Libervant™ is a buccally, or inside of the cheek, administered film formulation of diazepam, a benzodiazepine intended for the acute treatment of intermittent, stereotypic episodes of frequent seizure activity that are distinct from a patient’s usual seizure pattern in patients with epilepsy 12 years of age and older. Aquestive developed Libervant as an alternative to the device-based products currently available for patients with refractory epilepsy, including a rectal gel and nasal spray products. Approximately 1.0 million patients with epilepsy suffer from uncontrolled refractory seizures, approximately 85% of whom will not interact with the available treatments.

About Aquestive Therapeutics
Aquestive Therapeutics, Inc. is a pharmaceutical company advancing medicines to solve patients’ problems with current standards of care and provide transformative products to improve their lives. We are developing orally administered products to deliver complex molecules, providing novel alternatives to invasive and inconvenient standard of care therapies. Aquestive has five commercialized products on the U.S. market, four licensed products and one stand-alone proprietary product to date, Sympazan® (clobazam) oral film for the treatment of seizures associated with Lennox-Gastaut syndrome. Our licensees market their products in the U.S. and around the world. The Company also collaborates with pharmaceutical companies to bring new molecules to market using proprietary, best-in-class technologies, like PharmFilm®, and has proven drug development and commercialization capabilities. Aquestive is advancing a late-stage proprietary product pipeline focused on treating diseases of the central nervous system, or CNS, and an earlier stage pipeline for the treatment of severe allergic reactions, including anaphylaxis.


Welcome to Pharmaprojects’ 2023 review of trends in pharmaceutical R&D. For over 30 years now, I’ve been taking an annual look at the evolution of pharma R&D, and in this article, I’llexamine the state of play at the start of 2023.


Welcome to Pharmaprojects’ 2023 review of trends in pharmaceutical R&D. For over 30 years now, I’ve been taking an annual look at the evolution of pharma R&D, and in this article, I’llexamine the state of play at the start of 2023.

Related News


Patsnap Unveils Synapse Visitor, the Latest AI-Powered Pharmaceutical Intelligence Platform

Prnewswire | April 25, 2023

On April 20, Patsnap, the world's leading SaaS provider for intelligence, announced the launch of its latest version of the intelligence platform, Synapse, available to visitors. This version includes advanced search functions for drugs and pharmaceutical organizations, now publicly accessible for the first time. Users can explore these features without prior registration, making searching easier and more accessible than ever before. Synapse is an innovative Life Sciences Platform that uses AI technology to connect Drug Discovery information with Drug Development insights. This allows professionals in the pharmaceutical industry to make better-informed decisions throughout the entire innovation cycle. With a vast database of millions of free data points from over 150 jurisdictions, Synapse provides access to over 72,000 new drugs, 800,000 clinical trials, 6 million pharmaceutical patents, 62 million literature sources, 360,000 pharmaceutical organizations, and more. This wealth of information is available to users to aid them in their research and decision-making processes. One of the key benefits of Synapse is its extensive database of drugs, particularly those in their preclinical or early developmental stages, which helps to mitigate potential risks for professionals in the pharmaceutical industry. "We want to ensure that we are only developing drugs that are efficiently managed, reducing the risks of failure at the later stages of development," said one of our key clients, the head of R&D. By having access to this valuable information, professionals can make more informed decisions and focus their efforts on drugs with a higher potential for success, ultimately saving time and resources. Available on Synapse's website as a free solution, key features include Drug Advanced Search:Quickly and accurately identify drugs based on specific criteria of interest. The search function covers global drug candidates and marketed drugs, and mines preclinical R&D intelligence in patents and literature to identify early competitive risks. Clinical Progress:Screen clinical trials by drugs, institutions, targets (multi-target), indications, clinical trial phase, and other conditions. Synapse collates data from 18 registries, including and WHO, giving users a global view of the clinical landscape. Playbook: Access multiple data sets with a single search, including Due Diligence and Find Organizations. This feature provides comprehensive and visualized insights into the organization's R&D preferences, drug pipeline, investments, financing, and more. Literature Search:With over 62 million literature records in the life sciences field, users can easily screen literature by drugs, targets, indications, authors, and other criteria. This feature allows for efficient and targeted research, saving time and increasing productivity. About Patsnap Founded in 2007, Patsnap is the company behind the world's leading AI-powered innovation intelligence platform. Patsnap provides global businesses with a connected, easy-to-use platform that helps them make better decisions in the innovation process. Customers are innovators across multiple industry sectors, including agriculture and chemicals, consumer goods, food and beverage, life sciences, automotive, oil and gas, professional services, aviation and aerospace, and education.

Read More


Sony and Astellas Enter into Collaborative Research Agreement to Discover a Novel ADC Platform for the Oncology Field

PRNewswire | May 17, 2023

Sony Corporation and Astellas Pharma Inc. announced that they have entered into a collaborative research agreement to discover a novel Antibody-Drug Conjugate (ADC) platform in oncology based on Sony's unique polymeric material, "KIRAVIA™*2 Backbone." ADC is expected to selectively deliver anti-cancer drugs to target cells, thereby increasing efficacy and reducing side effects caused by anti-cancer drugs attacking normal cells. The technology to create linkers which conjugates antibodies and drugs, is considered to be a key to development of a better-performing ADC. This collaborative research leverages the flexibility in design and resulting properties such as high capacity and solubility of KIRAVIA Backbone as a linker of ADC, to effectively deliver anti-cancer drugs to targeted cells in a stable manner, aiming to further enhance therapeutic efficacy by achieving high Drug-to-Antibody Ratio (DAR) etc. The two companies jointly began exploratory research of new linker technology aimed at creating a new ADC platform in July 2022, and the expected profile was obtained in feasibility studies using human cancer cells. Under this agreement, Sony and Astellas will jointly develop and optimize a new ADC platform using the KIRAVIA Backbone as a linker. In addition, Astellas will conduct non-clinical trials of development candidates. Furthermore, in order to build a drug discovery platform not limited to ADC, the two companies have agreed to continue discussions on expanding research partnerships to create new value by combining Sony's cutting-edge technology with Astellas' renowned pharmaceutical capabilities. "Sony's life science business has accumulated substantial knowledge in the field of cell analysis," said Katsunori Ogawa, Head of Life Science & Technology Business Unit at Sony Corporation. "Through this collaboration, Sony is striving to contribute to the medical and drug discovery fields and provide further social value by leveraging Sony's technological capabilities in the development of anti-cancer drugs therapy, which are expected to grow." "We are pleased to enter into a joint research agreement with Sony," said Yoshitsugu Shitaka, Ph.D., Chief Scientific Officer (CScO), Astellas Pharma Inc. "Astellas is working to create innovative drugs from a multifaceted perspective called the Focus Area approach*4, which identifies combinations of biology, therapeutic modality or technology and diseases with high unmet medical needs. The partnership will further strengthen our ability to utilize suitable modalities. It is our expectation that the collaboration will lead to the continuous creation of innovative drugs for patients around the world." ADC is a modality that combines an antibody and a small molecule such as an anti-cancer drug via a linker. It is expected to selectively deliver anti-cancer drugs to target cells, thereby reducing side effects caused by anti-cancer drugs attacking normal cells. KIRAVIA™ and KIRAVIA Dyes™ are registered trademarks or trademarks of Sony Group Inc. or its affiliates. KIRAVIA Backbone is created using the organic polymer technology cultivated in KIRAVIA Dyes™, which Sony independently developed and licensed to reagent manufacturers. It features a high degree of freedom in design, as the three-dimensional structure is programmed and polymerized using an automatic synthesizer. While increasing the number of drugs to be added and cleaving by reacting with intracellular enzymes. Synthesis of linkers with functional properties and selective drug release is expected. About Astellas Astellas Pharma a pharmaceutical company conducting business in more than 70 countries around the world. We are promoting the Focus Area Approach that is designed to identify opportunities for the continuous creation of new drugs to address diseases with high unmet medical needs by focusing on Biology and Modality. Furthermore, we are also looking beyond our foundational Rx focus to create Rx+® healthcare solutions that combine our expertise and knowledge with cutting-edge technology in different fields of external partners. Through these efforts, Astellas stands on the forefront of healthcare change to turn innovative science into VALUE for patients.

Read More


Closed Loop Medicine and Pharmanovia enter a co-development partnership for precision medicine combination therapeutics

Businesswire | May 22, 2023

Closed Loop Medicine Ltd, a leading TechBio company, developing combination prescription drug plus software therapy products that enable personalized dose optimization, and Pharmanovia, a global pharmaceutical company that commercializes novel medicines and revitalizes, extends and expands the lifecycle of established medicines, today announced that they have entered a global co-development partnership. The partnership will initially focus on the development and launch of a drug + software combination version of a first-line anti-hypertensive in the UK, before phased global roll-out and additional therapies are added. Hypertension is the leading preventable cause of morbidity and premature death worldwide, impacting over 1 in 4 men and 1 in 5 women, and costing the NHS alone over £2.1 billion/year (1, 2). Managing high-blood pressure through medication and lifestyle modifications significantly reduces associated health risks and improves quality of life; research in the US demonstrating improved standards of care could prevent 91,900 heart attacks, 139,000 strokes and 115,400 cardiovascular deaths within just 5 years (3). However, poor drug tolerability and treatment-related side effects significantly impact adherence, with less than 50% of patients maintaining their treatment regimen after a year, ultimately hindering treatment effectiveness, patient outcomes and overall disease management (4). As part of this partnership, Closed Loop Medicine’s proprietary Software-as-a-Medical Device (SaMD) dosing optimization technology will be combined with Pharmanovia’s established anti-hypertensive medicines, under a single prescription. Recent preliminary clinical trial results have demonstrated that Closed Loop Medicine’s technology may provide the ability to dose optimize drug therapy, improve blood pressure control, and minimize side effects (5). By developing a new class of combination products for the treatment of hypertension, both companies aim to support patients and healthcare professionals to better manage high blood pressure. Dr. Hakim Yadi OBE, CEO & Co-Founder of Closed Loop Medicine, commented: “This pioneering partnership is a great example of where the power of software integration can add value to iconic medicines to make them more effective for patients. Through this co-development agreement, we will bring our IP, insight and technical know-how of dose optimized drug plus software integration alongside Pharmanovia’s innovative business model, to enable well-known and trusted brands to be positioned as value-driven precision medicine product solutions globally.” Dr. James Burt, CEO of Pharmanovia, said: “Combining our experience in lifecycle management with Closed Loop Medicine’s unique approach and technology is an exciting next step in our strategy. It enables us to use innovative technology to enhance established medicines and bring much needed innovation to an area of large-scale unmet need. Together we aim to deliver a first in class combination regulated software and medicine – with the aim of delivering better patient outcomes, while enabling healthcare systems to reduce costly hospital procedures through better adherence and patient engagement.” AboutPharmanovia Pharmanovia is a global lifecycle management healthcare company. Our purpose is to make medicines fit for tomorrow, to improve the lives of patients globally. We do this by enhancing established medicines either by rediscovering, repurposing or re-engineering iconic brands to improve patient outcomes and experiences both through in-house development and through strategic partnerships.

Read More