Aquestive outlines the path forward for Anaphylm, its oral epinephrine film for anaphylaxis, after an FDA CRL, with NDA resubmission planned in 2026 and continued pipeline progress
Written By: Pharmacally Medical News Desk
Aquestive Therapeutics has outlined its regulatory and development strategy to advance Anaphylm (dibutepinephrine) Sublingual Film, an investigational oral epinephrine therapy for severe allergic reactions, following the U.S. FDA’s Complete Response Letter (CRL) issued earlier this year.
In its fourth-quarter and full-year 2025 business update, the company reaffirmed confidence in the product’s potential and plans to resubmit the New Drug Application (NDA) in the third quarter of 2026, pending completion of additional studies requested by the regulator.
Anaphylm is being developed as a non-device, sublingual epinephrine rescue therapy for the treatment of Type I allergic reactions, including life-threatening anaphylaxis. If approved, it could become the first orally delivered epinephrine product, offering a needle-free alternative to traditional auto-injectors. The thin film is placed under the tongue and is designed to rapidly deliver epinephrine without requiring injection devices, which the company believes could improve accessibility, usability, and patient preference during emergency allergic reactions.
On January 30, 2026, the FDA issued a CRL for the Anaphylm NDA covering patients weighing 30 kilograms or more. The agency’s feedback was primarily related to human factors validation, highlighting potential challenges associated with opening the pouch and correctly placing the film. The FDA also requested a single pharmacokinetic (PK) study to evaluate the effect of packaging and labeling modifications.
The agency did not raise concerns regarding clinical comparability with epinephrine auto-injectors, chemistry, manufacturing, or controls, and no additional clinical efficacy trials were requested. According to the FDA, the required human factors validation and PK studies may be conducted in parallel.
To address these, Aquestive plans to conduct a new human factors validation study along with a supporting PK study, while engaging with regulators through a Type A meeting with the FDA to confirm the most efficient path forward. The company anticipates resubmitting the NDA in the third quarter of 2026 and intends to request an accelerated review, although expedited review status will ultimately depend on FDA determination.
Despite the regulatory setback, Aquestive continues to prepare for a potential launch of Anaphylm. The company is focusing on optimizing market access strategies in the United States, expanding medical affairs engagement and scientific presentations throughout 2026, and advancing global regulatory preparations, including ongoing engagement with regulators in Canada and early preparatory work for future submissions in the European Union. These activities aim to position Anaphylm for broader international access if approved.
As part of strengthening its leadership ahead of potential commercialization, the company recently appointed Dr. David Greenhawt, an internationally recognized allergy and immunology expert, as Chief Medical Officer. The appointment is intended to enhance the company’s clinical leadership as it advances Anaphylm and expands its presence in the allergy treatment landscape.
Beyond Anaphylm, Aquestive also reported progress in its pipeline. The company’s AQST-108 topical epinephrine prodrug gel, which is being explored for alopecia areata and other localized dermatologic conditions, received Investigational New Drug (IND) clearance from the FDA in December 2025.
An initial first-in-human study evaluating topical application and systemic exposure reported no serious or topical adverse events. The company has since completed dosing in a second Phase 1 clinical study, with data expected in the second quarter of 2026.
The topical formulation is designed to act locally at the application site, potentially reducing systemic exposure compared with currently available systemic therapies.
Reference
Aquestive Therapeutics Reports Fourth Quarter and Full Year 2025 Financial Results and Provides Business Update, 04 March 2026, Aquestive Therapeutics Reports Fourth Quarter and Full Year 2025 Financial Results and Provides Business Update – Aquestive Therapeutics