Aquestive Therapeutics, Inc. announced today that the US Food and Drug Administration (FDA) issued a Complete Response Letter (CRL) regarding the New Drug Application (NDA) for Anaphylm™ (dibutepinephrine). A CRL is an official communication from the FDA to a pharmaceutical company indicating that a New Drug Application (NDA) will not be approved in its current form. It outlines the specific deficiencies and issues the agency identified during its review that must be addressed before the application can proceed.
The sublingual film is designed as a non-invasive treatment for Type I allergic reactions, including anaphylaxis, in patients weighing 30kg or more. Although the CRL marks a regulatory setback, the company emphasized that the FDA’s concerns are limited to specific areas rather than the drug’s fundamental safety or efficacy.
The primary deficiencies cited by the FDA involve human factors (HF) validation and administration. Specifically, the Agency noted instances in which participants had difficulty opening the product’s pouch or placing the film incorrectly. The FDA expressed concern that these issues, if left unaddressed, could pose significant safety risks during an emergency anaphylactic event. Notably, the CRL did not raise concerns about the drug’s Chemistry, Manufacturing, and Controls (CMC) or the comparability data previously submitted.
In response to the feedback, Aquestive has already begun modifying the pouch opening mechanism, labeling, and instructions for use. To meet the FDA’s requirements, the company plans to conduct a new HF validation study and a single pharmacokinetics (PK) study to confirm that these packaging changes do not affect drug delivery. CEO Daniel Barber remained optimistic, stating, “While it is unfortunate to have received a CRL, we believe that, with the clarity we now have from the FDA, we have made significant progress toward approval.”
The company intends to move quickly and has requested a Type A meeting with the FDA to align on the most efficient path forward. Aquestive estimates it will be ready to resubmit the NDA as early as the third quarter of 2026, assuming studies are completed on schedule. Management reiterated its confidence in the product’s potential, with Barber adding, “We remain confident in the effectiveness and safety of Anaphylm and its potential as an easy-to-use, easy-to-carry, fast-acting epinephrine treatment”.
Medical professionals involved in the clinical program also voiced continued support for the platform. Dr Jay Lieberman, a practicing allergist and investigator, noted that the FDA’s focus is primarily on the “patient experience” rather than clinical failure. Lieberman remarked, “Given the continued underuse of epinephrine in anaphylaxis, the availability of more treatment options remains a top priority for clinicians and the allergy community.”
Beyond the United States, Aquestive is maintaining its global expansion timeline. The company plans to submit marketing applications in Canada and the European Union in the second half of 2026. The European Medicines Agency (EMA) has already indicated that no additional clinical trials will be required for the submission. Financially, the company reported that it remains well-capitalized to fund the remainder of the US approval process and its international ambitions.
Anaphylm represents a significant departure from traditional epinephrine delivery, utilizing a polymer matrix-based film about the size of a postage stamp. It dissolves on contact without the need for water or swallowing, offering a portable, needle-free alternative to auto-injectors. Aquestive will host an investor conference call on February 2, 2026, to discuss these regulatory developments in further detail.
