Aquestive Therapeutics said the U.S. Food and Drug Administration has issued a Complete Response Letter (CRL) for its New Drug Application seeking approval of Anaphylm, an investigational sublingual epinephrine film intended to treat severe allergic reactions, including anaphylaxis, in patients weighing at least 30 kilograms.
The agency’s decision does not reject the therapy outright but requires additional information before approval can be granted. According to the company, the FDA’s concerns center primarily on human factors and labeling issues rather than manufacturing or core clinical efficacy data.
Regulators identified problems in the product’s usability study, including difficulty opening the packaging and incorrect placement of the film under the tongue. The FDA warned these issues could create safety risks during emergency allergic reactions if patients are unable to administer the treatment quickly and correctly. To address the concerns, Aquestive has modified the pouch design, updated instructions for use and revised labeling, and plans to conduct a new human factors validation study. The agency also requested a single pharmacokinetic study to confirm that the changes do not affect drug absorption.
The company said both studies can be performed simultaneously and that no additional clinical trials were requested. It plans to request a Type A meeting with the FDA to determine the most efficient path toward resubmission and expects to refile the application in the third quarter of 2026, assuming study completion and typical review timelines.
Anaphylm is designed as a needle-free alternative to traditional epinephrine auto-injectors, delivering medication through a dissolvable oral film placed under the tongue. The therapy has been evaluated in 11 clinical studies involving 411 participants and nearly 1,000 administrations, demonstrating pharmacokinetic results comparable to existing injectable products, according to the company.
Aquestive is also pursuing approvals internationally, with regulatory discussions underway in Europe, Canada and the United Kingdom. The company expects to submit applications in Europe and Canada in the second half of 2026.
If approved, Anaphylm could become the first non-invasive oral epinephrine treatment for life-threatening allergic reactions, potentially offering a more portable and user-friendly option for patients and caregivers.