Sublingual epinephrine film produced greater cardiovascular responses than autoinjectors despite lower systemic exposure levels, HCPLive reported on Friday.
The findings emerged from an analysis of the investigational drug AQST-109, also known as dibutepinephrine or Anaphylm. Aquestive Therapeutics is developing the sublingual film for type I allergic reactions including anaphylaxis.
The U.S. Food and Drug Administration set a Prescription Drug User Fee Act goal date of March 16, 2027, for the new drug application resubmission, according to company announcements. Researchers presented the data at the American College of Allergy, Asthma and Immunology 2026 Annual Scientific Meeting held from November 12 to 16, 2026, in Phoenix, Arizona.
Low-Exposure Analysis Results
Healthy adults in the lowest Cmax tertile who received AQST-109 achieved a geometric mean maximum concentration of 117.51 pg/mL with a 95% confidence interval of 107.2 to 128.1 pg/mL. That concentration stayed below reference products administered across three separate studies: EpiPen, Auvi-Q, and manual intramuscular epinephrine.
Median time to maximum concentration reached 20 minutes with a range of 5 to 120 minutes. That speed matched autoinjectors and outpaced manual intramuscular injections.
Median maximum systolic blood pressure, diastolic blood pressure, and mean arterial pressure were higher with the sublingual film than with all three reference products. The time required to reach peak blood pressure measurements also moved faster with the film than with each comparator.
AQST-109 Heart Rate Compares to Epinephrine Delivery
Peak heart rate in the lowest exposure tertile was higher with AQST-109 than with intramuscular epinephrine and similar to both autoinjector devices. Time to maximum heart rate beat manual intramuscular delivery, matched EpiPen performance, and tracked closely with Auvi-Q.
“We’re treating people who need to have cardiovascular support in their anaphylactic reaction,” said David Golden, who reported disclosures involving Aquestive Therapeutics and ARS Pharmaceuticals Operations.
“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 told HCPLive.
Questions About Epinephrine Absorption
The analysis challenges assumptions that lower systemic absorption equates to a weaker clinical effect for sublingual films. Golden said that epinephrine only needs to reach an effective therapeutic threshold rather than peak concentration.
“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.”
Researchers have not fully mapped the mechanism driving stronger cardiovascular responses at lower systemic exposure levels. Sublingual and intranasal delivery routes create response patterns that differ from intramuscular administration, where localized muscle responses influence both drug absorption and systemic effects.
Anaphylm Development Questions
What is AQST-109?
AQST-109 is an investigational sublingual epinephrine prodrug film developed under the name Anaphylm for type I allergic reactions and anaphylaxis.
What does the PDUFA date mean for the drug?
The FDA established a PDUFA goal date of March 16, 2027, to complete its review of the resubmitted new drug application from Aquestive Therapeutics.
Does a low Cmax indicate treatment failure?
Low systemic exposure does not predict a weaker clinical response for this sublingual film because the drug achieves necessary blood pressure and heart rate changes below maximum concentration thresholds.
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