On September 17, 2026, Aquestive Therapeutics resubmitted its New Drug Application (NDA) to the US Food & Drug Administration (FDA) for Anaphylm (dibutepinephrine) sublingual film, a needle-free epinephrine product for type I allergic reactions, including anaphylaxis.¹ The resubmission follows a Complete Response Letter (CRL) the FDA issued on January 30, 2026, one that centered on how patients handled the product, not on whether it worked.²
The rejection was about the packaging and how patients handled it in testing, not about whether the drug worked.² That is an important distinction for anyone counseling patients on their options. This FAQ covers what actually happened, what changed in the resubmission, and what to tell patients who ask about it now.
The News: Aquestive Resubmits NDA for Anaphylm
Q: What did Aquestive just announce?
On September 17, 2026, Aquestive Therapeutics announced it had resubmitted its NDA to the FDA for Anaphylm sublingual film, addressing the deficiencies identified in the agency's January CRL.¹ The FDA will determine the resubmission's review classification and timeline following its initial review, so a new decision date is not yet set.¹
Q: What was actually wrong with the original Anaphylm application?
The CRL, issued January 30, 2026, cited deficiencies in the human factors validation study, not the drug's pharmacology, safety, or manufacturing.³ Specifically, participants in that study had difficulty opening the product's pouch, incorrectly placed the film, and, in some cases, chewing it or removing it after administration. The FDA said these issues could create safety risks during an actual anaphylactic event.³
What Changed with Anaphylm’s NDA
Q: What did Aquestive actually fix before resubmitting?
Aquestive redesigned the pouch opening along with the instructions for use and pouch and carton labeling in direct response to the deficiencies identified in the CRL.4 A follow-up human factors study using the revised packaging reduced the median pouch-opening time from 17 seconds to 3 seconds.4 A confirmatory pharmacokinetic study in healthy volunteers, using the revised packaging, then assessed both self-administration and clinician administration against manual intramuscular epinephrine as a comparator, and reported no protocol-defined use errors in the self-administration arm.4
Q: Does this mean the resubmission is likely to be approved?
It's a meaningfully stronger package than what the FDA rejected in January, since it directly targets the specific failure points the agency identified rather than resubmitting unchanged data. But the FDA has not yet set a review classification or timeline for the resubmission, and approval is not guaranteed.¹ Clinicians and patients should treat this as active progress, not as a settled outcome.
The Underlying Data: Oral Allergy Syndrome (OAS) Challenge Study
Q: Setting the CRL aside, how well does Anaphylm actually perform?
The product's underlying efficacy data were never in question. Across > 10 clinical studies and close to 1,000 administrations in hundreds of subjects, including single-dose and repeat-dose regimens, dibutepinephrine has shown a pharmacodynamic response comparable to, or in some analyses greater than, auto-injectors and manual intramuscular epinephrine.1,5 In an oral allergy syndrome challenge study, symptom resolution began within 2 minutes of administration, with roughly half of patients experiencing resolved symptoms by 5 minutes.6
Q: What does Anaphylm actually look and feel like to use?
It's a sublingual film, roughly the size of a postage stamp and weighing less than an ounce, that begins dissolving on contact and requires no water or swallowing to administer.7 Its packaging is designed to be thinner and smaller than a standard credit card and built to withstand weather exposure, a practical consideration for a product patients are meant to carry at all times.
Practical Guidance for Anaphylm
Q: How should a clinician talk to a needle-averse patient about Anaphylm right now?
It's reasonable to mention that a needle-free oral option remains in active FDA review and has shown strong efficacy data, while being clear it isn't available to prescribe yet.
Allergist and lead author of the 2023 Anaphylaxis Practice Parameter David Golden, MD, from Johns Hopkins, framed epinephrine counseling around 3 questions patients are really asking, whether they use those words or not: “Will it work? Can I trust it? Is it dangerous?” Golden noted that those questions don't change based on which delivery device a patient eventually uses.8
Q: Does this change what a clinician should prescribe today for anaphylaxis?
No. Until Anaphylm is approved, the calculus for currently available options, auto-injectors and the already-approved intranasal spray, is unchanged. The most important predictor of outcomes remains whether a patient will actually carry and use whatever device they're prescribed, not which one is theoretically fastest.8
Q: Is a broader anaphylaxis guideline update coming to address this expanding menu of delivery options?
Not yet, and not soon. Golden noted that a revision to the anaphylaxis practice parameter covering the expanding field of alternative delivery routes will require published, peer-reviewed real-world data across these newer products before it can be written, which puts a formal update years away rather than months.8
This FAQ reflects the regulatory status of Anaphylm (dibutepinephrine) sublingual film as of September 2026. Anaphylm is investigational and not yet FDA-approved; the FDA has not set a review classification or timeline for the September 2026 resubmission. Readers should confirm current status before relying on this content for clinical decisions, and prescribing information should always be checked against the current product label for any approved therapy referenced here.
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