The lowest tertile was compared against the reference products administered across the 3 studies, EpiPen, Auvi-Q, and manual IM epinephrine, using Kruskal-Wallis or Mann-Whitney U tests.¹ In this group, geometric mean Cmax was 117.51 pg/mL (95% CI, 107.2–128.1), below all reference products. Median time to maximum concentration (Tmax) was 20 minutes (range, 5–120), comparable to both autoinjectors and faster than IM epinephrine.
Despite the lower exposure, median Emax for SBP, DBP, and MAP was significantly greater with AQST-109 versus all 3 reference products.¹ Median TEmax for all 3 blood pressure measures was also faster versus each comparator.
Why Cmax May Not Predict Epinephrine Response
Frequently Asked Questions
What is AQST-109?
AQST-109, or dibutepinephrine (Anaphylm), is an investigational sublingual epinephrine prodrug film under FDA review for type I allergic reactions, including anaphylaxis, with a PDUFA goal date of March 16, 2027.²
What did the low-exposure analysis show?
Among healthy adults in the lowest Cmax tertile, AQST-109 produced significantly greater and faster SBP, DBP, and MAP responses versus EpiPen, Auvi-Q, and IM epinephrine.¹
Does a lower Cmax mean a weaker epinephrine response?
Not with AQST-109, according to this analysis. Golden noted epinephrine only needs to reach an effective threshold, and a greater Cmax does not by itself predict a better response.
Golden said the results challenge the assumption of a weaker clinical effect in patients with lower absorption, at least for the sublingual film. He cautioned the same conclusion cannot be drawn for IM injection.
“How high does it have to go to work, though? It doesn’t have to go to the Cmax,” Golden said. “The higher the Cmax doesn’t mean it’s going to work any better.”
The mechanism behind the stronger response at low exposure is not fully understood, according to Golden. He noted sublingual and intranasal routes produce response patterns distinct from IM delivery, in which localized responses within the muscle influence both absorption and the systemic effect of epinephrine.
Peak heart rate in the lowest tertile was significantly greater with AQST-109 compared with IM epinephrine and overlapped with both autoinjectors. ¹ Heart rate TEmax was faster than IM epinephrine, equal to EpiPen, and close to Auvi-Q.
“We’re treating people who need to have cardiovascular support in their anaphylactic reaction,” Golden said. “Athletes, for example, get high levels of epinephrine and high levels of heart rate and blood pressure during normal exercise for them. So these are all within physiologic range. They’re not dangerous.”
Editor’s note: Reported disclosures for Golden include AQUESTIVE THERAPEUTICS, ARS Pharmaceuticals Operations, and more.
References
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Golden D, Anagnostou A, Sokol K, Mack D, Rance K, Greenhawt M. Pharmacodynamic effects of sublingual epinephrine film AQST-109 at low systemic epinephrine exposures. Presented at: American College of Allergy, Asthma & Immunology 2026 Annual Scientific Meeting; November 12-16, 2026; Phoenix, AZ.
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Aquestive Therapeutics announces FDA acceptance of Anaphylm NDA resubmission and PDUFA goal date of March 16, 2027. Aquestive Therapeutics. Published October 15, 2026. Accessed November 13, 2026.