Sublingual epinephrine film AQST-109 achieved faster and stronger cardiovascular responses than standard comparators among healthy adults in the lowest systemic exposure tertile, HCPLive reported.
The analysis compared the lowest tertile against reference products administered across three studies. These reference products included EpiPen, Auvi-Q, and manual intramuscular epinephrine, using Kruskal-Wallis or Mann-Whitney U tests.
In this group, the geometric mean maximum concentration was 117.51 picograms per milliliter, with a 95% confidence interval of 107.2 to 128.1. This figure fell below all reference products.
Median time to maximum concentration was 20 minutes, with a range spanning from 5 to 120 minutes. This speed was comparable to both autoinjectors and faster than intramuscular epinephrine.
Cardiovascular Response Benchmarks
Despite the lower systemic exposure, the median maximum effect for systolic blood pressure, diastolic blood pressure, and mean arterial pressure was significantly greater with AQST-109 versus all three reference products.
The median time to maximum effect for all three blood pressure measures was also faster compared with each comparator.
Peak heart rate in the lowest tertile was significantly greater with AQST-109 than with intramuscular epinephrine. It also overlapped with both autoinjectors.
Heart rate time to maximum effect was faster than intramuscular epinephrine, equal to EpiPen, and close to Auvi-Q.
Epinephrine Reaches an Effective Threshold Without Maximum Concentration
These results call into question the presumption that lower absorption translates to a diminished clinical response, at least regarding the sublingual film format.
“How high does it have to go to work, though? It doesn’t have to go to the Cmax,” David Golden said. “The higher the Cmax doesn’t mean it’s going to work any better.”
Golden said that epinephrine only needs to reach an effective threshold, adding that a greater maximum concentration does not by itself predict a better response.
The mechanism behind the stronger response at low exposure is not fully understood.
Sublingual and intranasal routes produce response patterns distinct from intramuscular delivery. Intramuscular delivery involves localized responses within the muscle that influence both absorption and the systemic effect of epinephrine.
“We’re treating people who need to have cardiovascular support in their anaphylactic reaction,” Golden told HCPLive.
“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,” Golden said.
FDA Reviews Anaphylm for Type I Allergic Reactions
AQST-109, also known as dibutepinephrine or Anaphylm, is an investigational sublingual epinephrine prodrug film. It is currently under review by the Food and Drug Administration for type I allergic reactions, including anaphylaxis.
The agency set a Prescription Drug User Fee Act goal date of March 16, 2027.
Aquestive Therapeutics announced the FDA acceptance of Anaphylm NDA resubmission on October 15, 2026.
The data were presented at the American College of Allergy, Asthma & Immunology 2026 Annual Scientific Meeting held from November 12 to 16, 2026, in Phoenix, Arizona.
Frequently Asked Questions About AQST-109
What is AQST-109?
Anaphylm (dibutepinephrine), also designated as AQST-109, is an experimental sublingual epinephrine prodrug film currently undergoing regulatory evaluation by the FDA for type I allergic reactions—including anaphylaxis—with a target PDUFA date of March 16, 2027.
What did the low-exposure analysis show?
Among healthy adults in the lowest Cmax tertile, AQST-109 produced significantly greater and faster systolic, diastolic, and mean arterial blood pressure responses versus EpiPen, Auvi-Q, and manual intramuscular epinephrine.
Does a lower Cmax mean a weaker epinephrine response?
Not according to this analysis, which said that epinephrine only needs to reach an effective threshold and that a greater Cmax does not by itself predict a better response.
