Drug Update · Emergency Medicine

AQST-109: 12-Min Median T_max vs EpiPen in Phase 3 PK Study

July 17, 2026

drug

AQST-109 (epinephrine sublingual film)

primary_result

median time-to-maximum plasma concentration 12 minutes (AQST-109) vs 20 minutes (EpiPen) [2]

study

Phase 3, 2-part, open-label PK/PD study comparing AQST-109 with manual intramuscular injection, EpiPen, and Auvi-Q [2]

Clinical Perspective

Clinicians who treat allergic reactions and anaphylaxis, including emergency physicians, allergists, and primary care clinicians, should note that AQST-109 is a late-stage sublingual epinephrine film studied as a needle- and device-free alternative to intramuscular epinephrine ^[2]. The phase 3 PK/PD data support that AQST-109 can achieve PK exposures bracketed within approved intramuscular epinephrine and autoinjectors and reaches peak plasma concentration more rapidly than EpiPen in healthy adult testing, supporting further consideration of noninjectable epinephrine routes as alternatives to injectors in selected contexts ^[2]^[1]. Whether AQST-109 will be approved by regulatory authorities or how it will be positioned relative to available autoinjectors and intranasal products is not reported in the provided source excerpts ^[1]^[2].

Dr. Tanvi Deshmukh · Emergency Medicine

AQST-109, a needle- and device-free sublingual epinephrine film, demonstrated a median time-to-maximum plasma concentration of 12 minutes versus 20 minutes for EpiPen in a phase 3 pharmacokinetic/pharmacodynamic study ^[2]. The study met its primary PK bracketing end points for maximum serum concentration and partial area under the curve within 60 minutes, exceeding manual intramuscular injection, equaling EpiPen, and lower than Auvi-Q ^[2].

Clinical Context

Epinephrine administered intramuscularly in the thigh has been the preferential route for treatment of severe allergic reactions including anaphylaxis, but noninjectable routes are under active study ^[1]. AQST-109 is described in late-stage clinical development as a needle- and device-free sublingual alternative formulation of epinephrine intended to provide a portable option for epinephrine delivery ^[2]. Pharmacokinetic and pharmacodynamic data for noninjectable routes, including intranasal and sublingual formulations, suggest these routes can achieve epinephrine levels comparable with intramuscular autoinjectors, and the intranasal route has been reported as recently approved by regulatory agencies ^[1]. EpiPen remains an established intramuscular autoinjector with an indicated dose of 0.3 mg for patients greater than or equal to 30 kg (66 lbs) per its prescribing information ^[3]. Clinicians should consult current prescribing information for full dosing guidance.

Key Findings

The phase 3 study of AQST-109 met the primary PK end points of maximum serum concentration and partial area under the curve, with single-dose AUC and maximum serum concentration bracketed within 60 minutes, exceeding manual intramuscular injection, equaling EpiPen, and lower than Auvi-Q in the trial ^[2].
AQST-109 had a median time-to-maximum plasma concentration of 12 minutes compared with 20 minutes for EpiPen, 30 minutes for Auvi-Q, and 50 minutes for intramuscular injection, with AQST-109 showing narrower interquartile range (more consistency) than comparators ^[2].
AQST-109 demonstrated more rapid and larger increases in blood pressure and heart rate than the comparators in the single-dose assessments, and repeat-dose AQST-109 produced greater than dose-proportional increases in PK and PD parameters that exceeded the comparators ^[2].
The authors reported that single-dose AQST-109 demonstrated PK exposures consistently bracketed within established levels for approved intramuscular epinephrine and autoinjectors, with a more rapid time-to-maximum plasma concentration and comparable PD responses, and concluded these results suggest AQST-109 represents a safe and effective alternative to injectable epinephrine that is more portable and needle free ^[2].

Safety & Tolerability

No serious adverse events were reported in the phase 3 AQST-109 study ^[2].

Study Design

The AQST-109 data derive from a 2-part, phase 3, open-label study comparing pharmacokinetics and pharmacodynamics of single dose and repeat doses of AQST-109 with epinephrine administered by manual syringe, EpiPen, or Auvi-Q autoinjector on different days ^[2]. PK and PD parameters were assessed over 360 minutes post-administration, and the primary end points were maximum serum concentration and partial area under the curve ^[2]. The study population is described as healthy adults in the source summary ^[2].

FAQ

Q1 What did the Phase 3 trial show?

The phase 3, open-label PK/PD study showed that single-dose AQST-109 met the primary PK bracketing end points for maximum serum concentration and partial area under the curve within 60 minutes, with AUC and maximum serum concentration exceeding manual intramuscular injection, equaling EpiPen, and lower than Auvi-Q. AQST-109 had a median time-to-maximum plasma concentration of 12 minutes and demonstrated more rapid and larger increases in blood pressure and heart rate than comparators. No serious adverse events were reported in the study.

Q2 Who was enrolled in the Phase 3 trial?

The provided source summary states the trial compared AQST-109 with intramuscular epinephrine and autoinjectors in healthy adults using single-dose and repeat-dose administrations; PK and PD parameters were assessed over 360 minutes post-administration. Additional enrollment details were not available in the provided source excerpts.

Q3 What were the side effects in the Phase 3 trial?

The phase 3 report explicitly states that no serious adverse events were reported. The provided source excerpts did not include a broader list of adverse events or event frequencies.

Q4 What does the Phase 3 trial mean for clinical practice?

The authors reported that AQST-109 produced PK exposures bracketed within established levels for approved intramuscular epinephrine and autoinjectors, with a faster median time-to-maximum plasma concentration than EpiPen and comparable PD responses, suggesting AQST-109 could represent a portable, needle-free alternative to injectable epinephrine; regulatory status and clinical availability were not reported in the provided source excerpts.

Clinicians should consult current prescribing information for complete dosing guidance.

AQST-109: 12-Min Median T_max vs EpiPen in Phase 3 PK Study

Direct Clinical Takeaway & Evidence Summary

AQST-109: 12-Min Median T_max vs EpiPen in Phase 3 PK Study

Clinical Perspective

Clinical Context

Key Findings

Safety & Tolerability

Study Design

FAQ

References

Get weekly clinical updates for Emergency Medicine in your inbox.

Related Clinical Updates

Improves Battlefield Care with Mobile Surgical Units

Verified HCP Portal