Sublingual epinephrine film moving forward, NDA anticipated by early next year

Key takeaways:

• Aquestive aims to submit a new drug application in the first quarter of 2025.
• The company hopes to launch in late 2025 or early 2026, pending FDA approval.

Aquestive Therapeutics expects to finish its final supportive study of its Anaphylm sublingual epinephrine film for the treatment of anaphylaxis by the end of 2024.

Epinephrine is traditionally delivered via an injection and most recently also through a nasal spray. In a race to create alternative and less-invasive epinephrine delivery methods, drug manufacturers aimed to find new ways in which to simplify and quicken the treatment for anaphylaxis. A sublingual epinephrine film, such as Anaphylm, has been shown to be a viable method.

Healio spoke with Dan Barber, MBA, CEO of Aquestive Therapeutics, about Anaphylm, how it works, when patients can access it and how it compares with other anaphylaxis treatments currently in the market.

Healio: Who are the target patients for Anaphylm?

Barber: As many as 40 million people in the U.S. are at chronic risk for acute anaphylactic episodes. Epinephrine can be lifesaving when administered quickly once anaphylaxis is recognized; however, studies show that patients, even when prescribed epinephrine, don’t have it available to use during anaphylaxis.

Anaphylm (epinephrine) sublingual film has the potential to be the first and only FDA-approved no-needle, no-device oral epinephrine product for treating severe allergic reactions, including anaphylaxis, if approved by the FDA. It addresses multiple issues with current therapeutic approaches, such as fear of needles, epinephrine autoinjector device use errors and, most importantly, failure by patients to carry and have immediate access to epinephrine during an allergy emergency.

Healio: Could you describe how Anaphylm works?

Barber: Anaphylm is the first and only orally delivered film product candidate using Aquestive’s novel prodrug of epinephrine. Anaphylm utilizes our proven PharmFilm technology, eliminating the need for needles or nasal administration. You can put the film on the bottom of your tongue or on the floor of your mouth. Anywhere in that general area will do. It then begins to dissolve on contact, delivering epinephrine with no water or swallowing needed.

Anaphylm is about the size of a postage stamp and weighs less than an ounce, easily fitting within a purse or wallet. I’ve tested this by carrying it in my pocket with other credit cards and inside the case on the back of my phone. The product is designed to be extremely convenient, address needle anxiety and simplify administration during severe allergy emergencies.

Healio: Could you provide some highlights from the data you have so far about its efficacy and safety?

Barber: So far, we’ve reported positive topline pharmacokinetic data from a self-administration study of Anaphylm in July and a temperature/pH study in June. Aquestive also released positive pivotal study results in March.

Based on our clinical data to date, Anaphylm works as quickly as EpiPen.

Our temperature/pH study data reinforce that Anaphylm has the potential to be seamlessly integrated into patients’ daily lives.

The bottom line is, our data continue to show that sublingual administration has the potential to deliver epinephrine in a safe and effective way under a variety of conditions, making it easier for patients and caregivers to carry and quickly administer during a life-threatening allergic event.

Healio: How do these data compare with autoinjectors and other epinephrine delivery methods?

Barber: Epinephrine is something people have tried to deliver orally for decades. If approved by the FDA, Anaphylm has the potential to be the first noninvasive, orally delivered epinephrine product candidate to demonstrate clinical results that are comparable to autoinjectors such as EpiPen (Pfizer) and Auvi-Q (Kaleo).

In terms of epinephrine absorption, our pivotal study indicates that Anaphylm is comparable to the leading autoinjectors immediately following administration, and our time to maximum concentration, or Tmax, is faster than the leading autoinjectors. We believe this performance is unprecedented among those alternate delivery options recently approved by the FDA and currently under development.

This also builds on compelling data generated from our prior studies, showing that sublingual administration provides rapid and sustained levels of epinephrine, similar to the FDA-approved treatments.

Healio: Does Anaphylm have any other performance advantages over these other methods?

Barber: We’ve already covered our clinical data, but another key point of differentiation is that our formulation is durable in real-world conditions. Currently approved epinephrine medical devices come in liquid form and are largely made up of water, whereas our film is only about 2% water. Products composed largely of water are subject to degradation in real-world conditions, such as high temperatures. That is one of the main reasons that epinephrine auto-injectors have such strict storage instructions. They may no longer be effective if they are left out in summer heat for an extended time.

As we have seen with our other products over the last 2 decades, oral films are different. Anaphylm’s low water content means it has the potential to remain stable even after long durations of heat or cold exposure. It means Anaphylm has the potential to work in a broad spectrum of real-world conditions, which we do not believe can be matched by any other existing or pipeline product in this category.

Anaphylm is an easy-to-carry and easy-to-use alternative to single-use medical devices, and Anaphylm’s simple, oral administration alleviates fears associated with traditional auto-injectors. This, in turn, helps prevent administration hesitancy and possible improper administration and suboptimal dosing.

Healio: From a practical use perspective, what advantages does Anaphylm have over other methods?

Barber: Research suggests that less invasive, easier-to-carry products may improve carry rates, treatment adherence and compliance. That’s why Anaphylm comes in a highly portable pouch with the durability to withstand many of the norms of daily life, including weather exposure. It’s easy to carry and keep everywhere you go, whether you’re headed to work, the beach or a restaurant.

Anaphylm has the potential to work across a broad spectrum of real-world conditions, which we don’t believe can be matched by any other existing or pipeline product in this therapeutic area. Its functionality is designed for real-world emergency scenarios during which ideal administration conditions may not exist.

We believe Anaphylm easily fits within patients’ daily lives given its unique product attributes. Additionally, with studies showing that devices are regarded as inconvenient to carry, it’s the ideal solution to help ensure patients have access to epinephrine — anytime, anywhere.

Healio: What is the next step in your research?

Barber: Aquestive has successfully completed two of the three supportive studies necessary for engaging the FDA in a pre-new drug application (NDA) meeting.

We’re currently conducting our remaining supportive study for Anaphylm, the oral allergy syndrome challenge study, where we actually expose people to an allergen. This is expected to be completed in the next 4 to 6 weeks.

Healio: Where is Anaphylm in its FDA approval process?

Barber: Earlier this spring, we announced the successful completion of a Type C meeting with the FDA. The FDA noted that substantial progress had been made in the Anaphylm clinical development program and didn’t outline any new clinical development requirements at that time.

We expect to submit an NDA to the FDA in the first quarter of 2025 with the potential for a product launch in late 2025 or early 2026, if approved by the FDA.

Healio: Do you have anything else to add?

Barber: Patients at risk for an allergic emergency need options that address their barriers to having epinephrine on hand and using it. We remain excited by the opportunity to address the significant unmet need for a convenient, orally delivered, safe and effective epinephrine product. No-needle, no-device Anaphylm offers the reliability of epinephrine combined with extreme convenience in terms of small packaging and simple administration. We believe Anaphylm is poised to transform the treatment of severe allergic reactions, including anaphylaxis, if approved by the FDA.

References:

• Aquestive Therapeutics announces pivotal study for Anaphylm (epinephrine) successfully meets primary and secondary endpoints and provides clinical development update following FDA meeting. https://investors.aquestive.com/news-releases/news-release-details/aquestive-therapeutics-announces-pivotal-study-anaphylmtm. Published March 14, 2024. Accessed Oct. 1, 2024.
• Aquestive Therapeutics reports positive topline data for Anaphylm (epinephrine) sublingual film from self-administration study. https://investors.aquestive.com/news-releases/news-release-details/aquestive-therapeutics-reports-positive-topline-data-anaphylmtm. Published July 25, 2024. Accessed Oct. 1, 2024.
• Aquestive Therapeutics reports positive topline data for Anaphylm (epinephrine) sublingual film from temperature/pH study of Anaphylm (epinephrine) sublingual film. https://investors.aquestive.com/news-releases/news-release-details/aquestive-therapeutics-reports-positive-topline-data-temperature. Published June 25, 2024. Accessed Oct. 1, 2024.
• Prince BT, et al. J Asthma Allergy. 2018;doi:10.2147/JAA.S159400.