Aquestive Therapeutics has officially resubmitted its New Drug Application (NDA) to the US Food and Drug Administration (FDA) for Anaphylm™ (dibutepinephrine) sublingual film. The investigational, needle-free polymer matrix film contains the epinephrine prodrug dibutepinephrine and is designed for the acute treatment of Type I allergic reactions, including life-threatening anaphylaxis.
The resubmission comes in response to a Complete Response Letter (CRL) issued by the FDA on January 30, 2026. In the CRL, the agency requested that Aquestive complete a human factors study addressing packaging and administration, along with a confirmatory pharmacokinetic (PK) study of Anaphylm.
To address the FDA’s concerns, Aquestive redesigned the product’s packaging and instructions for use. Recent topline human factors results showed significant improvements in accessibility, cutting the median time required to open the Anaphylm pouch from 17 seconds to just 3 seconds.
The confirmatory PK study evaluated both self-administration and clinician administration of Anaphylm using the revised packaging and instructions for use, with manual intramuscular (IM) epinephrine included as a comparator. Aquestive reported that no protocol-defined use errors occurred in the self-administration arm.
Company leadership underscored the significance of completing the additional work requested by the FDA. “This resubmission reflects the rigor of our response to the FDA’s Complete Response Letter, and we believe it addresses the items identified by the FDA in the Complete Response Letter,” said Daniel Barber, President and Chief Executive Officer of Aquestive Therapeutics.
David Golden, MDCM, lead author of the 2023 Anaphylaxis Practice Parameter and a member of Aquestive’s Scientific Advisory Board, emphasized the potential clinical significance of Anaphylm’s pharmacodynamic profile: “Importantly, Anaphylm has previously demonstrated a rapid onset together with robust increases in heart rate and blood pressure; these pharmacodynamic responses were comparable to or greater than those observed with auto-injectors and manual IM epinephrine in clinical studies. Taken together, these characteristics suggest that Anaphylm, if approved, could represent a meaningful advancement in the treatment of severe allergic reactions, including anaphylaxis.”
Engineered to be roughly the size of a postage stamp and weighing less than an ounce, Anaphylm begins to dissolve on contact with the tongue without requiring water or swallowing. Following its initial review, the FDA will determine the classification of the resubmission and set the applicable review timeline.
