NDA Submission for Anaphylm (Epinephrine) Sublingual Film on Track for Q1 2025, Company Says

Aquestive Therapeutics announced positive feedback from the FDA this week regarding the company’s planned new drug application (NDA) submission for Anaphylm (epinephrine) sublingual film to the agency in early 2025.¹

In a written response, the FDA agreed with the content the company outlined for the NDA as well as the format for the submission, according to a news release. The agency also endorsed the planned safety evaluation for Anaphylm as well as the design and scope of the single-dose pediatric trial now underway in the US and Canada.¹

Hospital admissions for anaphylaxis have increased between 500% and 700% in the past 10-15 years. Of individuals who had experienced anaphylaxis in the past, 52% had never been prescribed an epinephrine autoinjector, and of those who had, 60% of them did not have one available to use in the situation that brought them to the hospital.

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Further the FDA said it does not require the company to conduct additional adult clinical trials of the novel mode of epinephrine delivery before submission of the NDA. Given the new route of administration and the supporting data, the FDA also noted the possible need for an advisory committee meeting prior to a final decision, Aquestive said.¹

If Anaphylm receives FDA approval, it has the potential to be the first and only orally delivered epinephrine product for the treatment of severe allergic reactions, including anaphylaxis, according to the Aquestive press release. “We believe FDA alignment on the completeness of our adult development program for Anaphylm is a major milestone for the Company and the allergy community,” Daniel Barber, Aquestive president and chief executive officer, said in the release. With commencement of the pharmacokinetic/pharmacodynamic (PK/PD) pediatric trial this month, Barber said the company “has a clear path to an NDA submission in the first quarter of 2025.”¹

The FDA also provided guidance in its response letter on data views the agency wants included in the submission and re-emphasized its focus on the “pharmacokinetic sustainability of a single dose,” Aquestive reported.

Features, Benefits

Anaphylm, a trade name conditionally approved by the FDA is “a polymer matrix-based epinephrine prodrug candidate product.” The delivery vehicle is approximately the size of a US postage stamp and comes in packaging that is both thinner and smaller than a credit card. The product is highly portable, weighing less than 1 ounce and amenable to carrying in a pocket. The packaging is resistant to weather excursions including exposure to rain or direct sunlight, according to Aquestive.²

In addition to the pediatric trial now underway, completion of an oral allergy syndrome challenge is slated for completion before the end of this year. The company projects a full product launch of epinephrine sublingual film in late 2025 or early 2026.²

Anaphylaxis is a potentially fatal systemic hypersensitivity reaction that is a chronic condition for up to 49 million people within the US. Hospital admissions for anaphylaxis have increased between 500% and 700% in the past 10-15 years, according to the news release. Of individuals who had experienced anaphylaxis in the past, more than half (52%) had never been prescribed an epinephrine autoinjector, and of those who had, 60% of them did not have one available to use in the situation that brought them to the hospital.²

Epinephrine injection is the current standard of treatment to reverse the severe manifestations of anaphylaxis. The costs associated with the reaction are substantial with annual expenditures estimated at $1.2 billion, direct costs for epinephrine reaching $294 million and indirect costs of $609 million.²

NDA Component

A single dose, 3-period randomized cross over study of 36 healthy adult subjects compared PK and PD of the sublingual epinephrine when self-administered, when administered by a health care professional and against PK and PD after intramuscular injection of adrenaline by a health care professional.

While the median time to maximum concentration (Tmax) for IM adrenaline administered by a clinician was 50 minutes, Tmax for both self- and HCP-administered medication was just 15 minutes.²

The PK and PD data show “that rapid and substantial epinephrine absorption is achieved under a variety of administration conditions,” Barber said in an earlier news release.3 “This built-in functionality addresses potential real-world emergency scenarios, where ideal administration may not happen.”³

“Experiencing and managing a severe allergic reaction can be unsettling and chaotic for patients and caregivers. An orally administered product that can be rapidly and easily administered has the potential to be a game-changer for the allergy community,” Matthew Greenhawt, MD, MBA, MSc, an anaphylaxis expert, an allergist at Children’s Hospital Colorado, and a member of the Aquestive scientific advisory board, said in the same release.³ Greenhawt lauded several features of the sublingual film formulation that are important to both individuals and their caregivers including ease of administration, rapid delivery of epinephrine, no needles, and portability.³

References
1. Aquestive Therapeutics announces positive FDA feedback and reaffirms NDA submission guidance for Anaphylm (epinephrine) sublingual film. News release. Aquestive Therapeutics. December 2, 2024. Accessed December 3, 2024. https://investors.aquestive.com/node/10926/pdf
2. Halsey G. Topline PK data released on self-administered epinephrine sublingual film for severe allergy. Patient Care. July 26, 2024. https://www.patientcareonline.com/view/topline-data-released-on-self-administered-epinephrine-sublingual-film-for-severe-allergy
3. Aquestive therapeutics reports positive topline data for Anaphylm (epinephrine) sublingual film from self-administration study. News release. Aquestive. July 25, 2024. Accessed July 26, 2024. https://investors.aquestive.com/node/10716/pdf