Dibutepinephrine (Anaphylm) Meets Pharmacokinetic Goals in Anaphylaxis

Aquestive Therapeutics has reported positive topline results from a human factors validation study and a pharmacokinetic study of dibutepinephrine (Anaphylm) sublingual film, supporting the company's planned Q3 2026 resubmission of its New Drug Application (NDA) for Type 1 allergic reactions, including anaphylaxis.¹

The US Food & Drug Administration (FDA) issued a Complete Response Letter (CRL) on January 30, 2026, after participants in an earlier human factors study had difficulty opening the pouch, incorrectly placed the film, chewed it, or removed it after administration.¹ Aquestive redesigned the pouch opening, instructions for use, and pouch and carton labeling in response to those deficiencies.2 According to the company, Anaphylm would be the first non-invasive, orally delivered epinephrine product for patients at risk of life-threatening allergic reactions, if approved.¹

"For patients who are at risk of having a severe allergic reaction, having a package for your epinephrine that's easy to open in an emergency can make all the difference," said Matthew Greenhawt, MD, MBA, MSc, chief medical officer of Aquestive. "In our topline analysis, patients and caregivers were better able to use the revised packaging, and our pharmacokinetic data met the endpoints we set out to achieve."

Anaphylm Human Factors and Pharmacokinetic Study Design

The revised human factors study evaluated modifications to the pouch opening, instructions for use, and pouch and carton labeling intended to address the deficiencies identified in the CRL.¹ Median time to open the pouch fell from 17 seconds in the earlier study to 3 seconds in the new study.¹ The number of participants with difficulty opening the pouch dropped from 26 of 166 to 1 of 105, and incorrect film placement fell from 20 of 166 to 2 of 105.¹ No participants chewed or removed the film in the latest study.¹

Using the revised packaging, Aquestive also conducted a single pharmacokinetic study (AQ109109) in healthy volunteers comparing self-administration with clinician-administered Anaphylm and manual intramuscular (IM) epinephrine.¹ Geometric mean Cmax was 391.7 pg/mL for self-administered Anaphylm, 357.6 pg/mL for clinician-administered Anaphylm, and 334.5 pg/mL for manual IM administration.¹ Median Tmax was 12 minutes for both Anaphylm arms compared with 45 minutes for manual intramuscular administration.¹ No administration errors occurred in the self-administration arm.¹

Anaphylm Safety and Misplacement Pharmacodynamic Data

At the FDA's request, Aquestive also studied purposeful misplacement of Anaphylm on top of the tongue or roof of the mouth to assess pharmacokinetic, pharmacodynamic (PD), and tolerability effects of incorrect administration.¹ Compared with correct sublingual placement in prior studies, top-of-tongue placement produced a lower geometric mean Cmax and a longer median Tmax.¹ Top-of-tongue placement generated a geometric mean Cmax > 100 pg/mL (baseline unadjusted) and a median Tmax of 35 minutes, with pharmacodynamic effects on systolic blood pressure comparable to or greater in magnitude than those seen with injectable epinephrine.¹

No participants in the human factors study and no subjects in the pharmacokinetic study prematurely removed the film.¹ The pharmacokinetic study recorded no serious adverse events, no serious events, and no discontinuations attributed to study drug.¹ Aquestive said the tolerability findings, together with the human factors and pharmacokinetic data, support the planned NDA resubmission.¹

"Even if used incorrectly, such as placing on top of the tongue instead of under the tongue, the pharmacodynamic response is what you would want in an epinephrine product during an allergic reaction," said Jay Lieberman, MD, professor of pediatrics at the University of Tennessee Health Science Center, and a member of Aquestive's Scientific Advisory Board.

Aquestive plans to complete the Anaphylm NDA resubmission in the third quarter of 2026 and is advancing parallel regulatory submissions for the film in Canada, the United Kingdom, and the European Union.¹

References

1. Aquestive Therapeutics announces positive topline human factors and pharmacokinetic study results for Anaphylm (dibutepinephrine) sublingual film. Business Insider. Published August 10, 2026. Accessed August 10, 2026. https://markets.businessinsider.com/news/stocks/aquestive-therapeutics-announces-positive-topline-human-factors-and-pharmacokinetic-study-results-for-anaphylm-dibutepinephrine-sublingual-film-1036435289

2. Brooks A. FDA Issues CRL to Dibutepinephrine (Anaphylm) Sublingual Film for Type 1 Allergic Reactions. HCPLive. Published February 2, 2026. Accessed August 10, 2026. https://www.hcplive.com/view/fda-issues-crl-to-dibutepinephrine-anaphylm-sublingual-film-for-type-1-allergic-reactions