In a pooled analysis presented at the American College of Allergy, Asthma & Immunology meeting in Phoenix, researchers asked a question that has trailed a needle-free epinephrine film for some time: whether a patient who absorbs less of the drug under the tongue is necessarily treated less well. For AQST-109, the data from healthy adults suggest it may not be so, since the people with the lowest absorbed concentrations still showed blood pressure responses that matched or outpaced those of established injectors. The mechanism is not yet understood, and the finding belongs to the sublingual fil
AQST-109 Sublingual Epinephrine Delivers Stronger Blood Pressure Response Even at Low Systemic Exposure
The higher the Cmax doesn't mean it's going to work any better.
Mark
Why does a low Cmax finding matter so much?
Mimi
Because the worry about under-the-tongue epinephrine is that some people absorb little. This says even the lowest absorbers had strong blood pressure responses.
Mark
Stronger than injections?
Mimi
On systolic, diastolic, and mean arterial pressure, yes, and faster too, compared with EpiPen, Auvi-Q, and IM epinephrine.
Luke
Let's be careful. These are healthy adults, not people in anaphylaxis. Blood pressure response in volunteers isn't the same as treating a reaction.
Mimi
Fair. The source frames it as pharmacodynamic data, not clinical outcomes.
Mark
Does Golden explain why it works?
Mimi
He says the mechanism isn't fully understood. He points to route differences, like local muscle effects with IM delivery.
Luke
So that's a hypothesis, not a finding. And he's clear it doesn't extend to IM injection.
Mark
Any reason to read it with caution?
Luke
Golden has disclosed ties to Aquestive, and this is a presented analysis, not a decision. The FDA's March 16, 2027 date is where it gets tested.
Mimi
And heart rate was more mixed: higher than IM, overlapping with autoinjectors.
Il Polso
- The lowest-exposure group absorbed less epinephrine than every reference product, yet its blood pressure responses were significantly stronger, challenging a long-held assumption about how sublingual dosing should work.
- Heart rate responses were more mixed, exceeding IM epinephrine at peak but overlapping with both autoinjectors, leaving clinicians with a nuanced picture rather than a clean verdict.
- Investigators are offering a threshold explanation: once epinephrine reaches an effective level, higher peak concentrations add little, but the underlying mechanism remains unexplained.
- The FDA holds the next move, with a PDUFA goal date of March 16, 2027, following a prior complete response letter, and the findings cannot yet be extended to intramuscular injection.
In a pooled analysis presented at the American College of Allergy, Asthma & Immunology meeting in Phoenix, researchers asked a question that has trailed a needle-free epinephrine film for some time: whether a patient who absorbs less of the drug under the tongue is necessarily treated less well. For AQST-109, the data from healthy adults suggest it may not be so, since the people with the lowest absorbed concentrations still showed blood pressure responses that matched or outpaced those of established injectors. The mechanism is not yet understood, and the finding belongs to the sublingual film alone, awaiting the regulator's judgment by March 16, 2027.
At the American College of Allergy, Asthma & Immunology annual meeting in Phoenix, a pooled analysis of a needle-free epinephrine film revisited a stubborn question: if less drug reaches the bloodstream under the tongue, does the treatment work less well? Among healthy adults, the answer for this film appears to be no.
The product, AQST-109, is being developed by Aquestive Therapeutics as dibutepinephrine, sold under the name Anaphylm. The FDA accepted the company's resubmitted New Drug Application in October 2026, with a goal date of March 16, 2027, after an earlier complete response letter.
The researchers sorted participants from three studies by peak epinephrine concentration and examined the lowest third. That group's concentrations sat below every reference product, yet their median blood pressure responses were significantly greater than those produced by EpiPen, Auvi-Q, or manual intramuscular epinephrine, and arrived faster. Heart rate was more mixed: higher than IM at peak, overlapping with the autoinjectors.
David B.K. Golden of Johns Hopkins, a presenting author, argued that epinephrine only needs to reach an effective threshold, so a higher peak does not guarantee a better result. He was careful to say this cannot be assumed for injection, and he acknowledged the mechanism is not fully understood. He described the cardiovascular changes as within normal physiologic range, similar to those seen during exercise.
For now, the mechanism remains open, the study is limited to healthy volunteers, and the regulator's decision is the next marker.
At the American College of Allergy, Asthma & Immunology annual meeting in Phoenix, a pooled analysis of a needle-free epinephrine film took on a question that has followed the product for some time: if a patient absorbs less drug under the tongue, does the treatment work less well? The data, drawn from healthy adults, suggest that for this film the answer may be no.
The product is AQST-109, which Aquestive Therapeutics is developing as dibutepinephrine, sold under the name Anaphylm. It is an epinephrine prodrug delivered as a sublingual film. The US Food & Drug Administration accepted the company's New Drug Application resubmission in October 2026 and set a Prescription Drug User Fee Act goal date of March 16, 2027. The resubmission followed a complete response letter issued on January 30, 2026.
The analysis, presented at the meeting held November 12 to 16, was authored by David Golden, Aislinn Anagnostou, Sokol, Mack, Rance, and Greenhawt. It sorted participants across three studies into tertiles by peak epinephrine concentration, known as Cmax, and looked closely at the lowest third. Those participants were compared with people who received EpiPen, Auvi-Q, or manual intramuscular (IM) epinephrine, using Kruskal-Wallis or Mann-Whitney U tests.
In that lowest-exposure group, the geometric mean Cmax was 117.51 pg/mL (95% CI, 107.2 to 128.1), below the figure for every reference product. Median time to maximum concentration was 20 minutes, with a range of 5 to 120. That was comparable to both autoinjectors and faster than IM epinephrine.
The blood pressure findings ran against what the concentration numbers would predict. Median maximum effect for systolic, diastolic, and mean arterial pressure was significantly greater with AQST-109 than with all three reference products. The time to reach that maximum effect was also faster than with each comparator.
Heart rate told a slightly more mixed story. Peak heart rate in the lowest tertile was significantly greater than with IM epinephrine and overlapped with both autoinjectors. The time to peak heart rate was faster than IM epinephrine, equal to EpiPen, and close to Auvi-Q.
David B.K. Golden, MD, associate professor of medicine at Johns Hopkins University School of Medicine, told HCPLive that even people who get a low level of epinephrine into their system with AQST-109 can see a blood pressure and heart rate response as good as or better than with a full IM dose. His reasoning is that epinephrine only has to reach an effective threshold. "The higher the Cmax doesn't mean it's going to work any better," he said. He cautioned that this cannot be assumed for IM injection; the conclusion applies to the sublingual film.
Golden acknowledged that the mechanism is not fully understood. He noted that sublingual and intranasal routes produce response patterns distinct from IM delivery, where localized events within the muscle shape both absorption and the systemic effect. On safety, he said the heart rate and blood pressure changes sit within physiologic range, comparable to what athletes experience during exercise, and are not dangerous. Golden's reported disclosures include Aquestive Therapeutics and ARS Pharmaceuticals Operations.
The next marker is the FDA's decision, due by March 16, 2027. Until then, the unexplained mechanism and the limits of a healthy-volunteer analysis remain open.
Citazioni salienti
Even those who get a low level of epinephrine into their system with AQST-109 can get as good as or even better response in their blood pressure and heart rate as compared with the full dose of intramuscular epinephrine.— David B.K. Golden, MD, Johns Hopkins University School of Medicine
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