Aquestive Therapeutics resubmits Anaphylm NDA to FDA after human factors and PK studies, with pouch-opening time reduced from 17 to 3 seconds.
Written By: Asritha Thippavajjala, PharmD
Reviewed By: Pharmacally Editorial Team
Aquestive Therapeutics has resubmitted its New Drug Application (NDA) for Anaphylm (dibutepinephrine) sublingual film to the U.S. Food and Drug Administration (FDA) for the treatment of Type I allergic reactions, including anaphylaxis, after completing the human factors and confirmatory pharmacokinetic (PK) studies requested in the agency’s January 2026 Complete Response Letter (CRL). The revised packaging reduced median pouch-opening time from 17 seconds to 3 seconds in the human factors assessment.
NDA Resubmission Addresses FDA Requirements
The resubmission follows the FDA’s CRL issued on January 30, 2026, which requested additional evidence on Anaphylm’s packaging and administration. Specifically, the agency asked Aquestive to complete a human factors study and a confirmatory PK study.
Following the CRL, the company held a Type A meeting with the FDA to discuss its proposed approach for addressing the agency’s concerns. Aquestive subsequently completed both studies using revised packaging and updated instructions for use.
The human factors study evaluated modifications to the pouch opening, instructions for use, and pouch and carton labeling. The revised configuration reduced the median time required to open the product pouch from 17 seconds to 3 seconds.
Confirmatory PK Study Evaluated Self-Administration
The confirmatory PK study enrolled healthy volunteers and evaluated both self-administration and clinician administration of Anaphylm using the revised packaging and instructions. Manual intramuscular epinephrine was included as a comparator.
No protocol-defined use errors occurred in the self-administration arm of the PK study. The company announced the topline human factors and PK results in August 2026 and subsequently incorporated the findings into the resubmitted NDA.
The FDA will determine the classification of the resubmission and establish the applicable review timeline after its initial assessment. Aquestive has not announced a definitive FDA action date.
Anaphylm Uses a Sublingual Epinephrine Prodrug
Anaphylm contains dibutepinephrine, an epinephrine prodrug formulated as a polymer matrix-based sublingual film. The film begins to dissolve upon contact and does not require water or swallowing.
The formulation is intended to provide epinephrine through a needle-free route. Its primary packaging is thinner and smaller than an average credit card, while the film itself is approximately the size of a postage stamp and weighs less than an ounce.
The FDA has conditionally approved the Anaphylm proprietary name for AQST-109. Final approval of the trade name remains contingent on FDA approval of the product candidate.
Previous Studies Showed Pharmacodynamic Activity
Earlier clinical studies reported rapid onset of Anaphylm and increases in heart rate and blood pressure. According to the company, these pharmacodynamic responses were comparable to or greater than those observed with epinephrine auto-injectors and manually administered intramuscular epinephrine.
These findings provide pharmacodynamic support for continued development, but Anaphylm remains investigational and has not received FDA approval for the treatment of anaphylaxis or other Type I allergic reactions.
David B.K. Golden, M.D.C.M., lead author of the 2023 Anaphylaxis Practice Parameter and a member of Aquestive’s Scientific Advisory Board, emphasized that rapid access to epinephrine is critical during anaphylactic reactions. He noted that a portable, needle-free formulation could potentially address practical barriers associated with carrying and administering injectable epinephrine.
FDA Review Will Determine Next Milestone
Aquestive originally submitted the Anaphylm NDA in March 2025. The latest resubmission incorporates the additional human factors and PK evidence requested by the FDA.
Daniel Barber, president and CEO of Aquestive Therapeutics, said the company believes the new submission addresses the issues identified in the CRL and is preparing for a potential allergist-focused launch if FDA approval is granted.
The immediate regulatory milestone is the FDA’s initial review of the resubmitted NDA. The agency will determine the applicable resubmission classification and review timeline as part of that process. Until then, the timing of a potential regulatory decision remains undetermined.
Reference
Aquestive Therapeutics Announces Resubmission of New Drug Application to FDA for Anaphylm™ (dibutepinephrine) Sublingual Film, Aquestive, 17 September 2026
About the Writer
Aasritha Thippavajjala (Linkedin) is a pharm D student and aspiring medical writer with medical writing, clinical training experience and a strong interest in clinical research and patient safety She has hands-on exposure to clinical pharmacy activities including medication profile assessment, clinical case review, identification of potential drug-related problems, ADR awareness, patient counselling, and clinical documentation. She has also gained experience in medical literature review, evidence synthesis, and scientific communication through her published review article on digital twin-based patient simulation and her poster presentation at the 74th Indian Pharmaceutical Congress. Certified in ICH Good Clinical Practice (E6(R3)) and Scientific Writing in Health Research, she is passionate about applying her clinical knowledge and research skills to medical writing ,clinical research and contributing to accurate, evidence-based healthcare.