Pharmacokinetics and pharmacodynamics of AQST-109: Phase 3 results comparing epinephrine sublingual film with intramuscular injection.

BACKGROUND

Intramuscular epinephrine administered via manual injection, autoinjector, or as a nasal spray are the current first-line treatments for anaphylaxis. AQST-109 is a needle- and device-free sublingual alternative epinephrine formulation in late-stage clinical development.

OBJECTIVE

To compare the pharmacokinetics (PK) and pharmacodynamics (PD) of single dose and repeat doses (RD) of AQST-109 with intramuscular epinephrine in healthy adults.

METHODS

In this 2-part, phase 3, open-label study, participants received single dose and RD of AQST-109 and epinephrine via manual syringe, EpiPen, or Auvi-Q autoinjector on different days. PK and PD parameters were assessed in 360 minutes post-administration; primary end points were maximum serum concentration and partial area under the curve. Additional PK and PD end points including blood pressure and heart rate were also measured.

RESULTS

After single dose AQST-109 administration, area under the curve and maximum serum concentration met the primary end point of PK bracketing of 60 minutes, exceeding that of manual intramuscular injection, equaling EpiPen, but lower than that of Auvi-Q. AQST-109 had a median time-to-maximum plasma concentration of 12 minutes, exceeding that of EpiPen (20 minutes), Auvi-Q (30 minutes), and intramuscular injection (50 minutes); there was also more consistency (narrower IQR) than the comparators. AQST-109 demonstrated more rapid and larger increases in blood pressure and heart rate than the comparators. RD AQST-109 had greater than dose-proportional increases in PK and PD parameters, exceeding the comparators. No serious adverse events were reported.

CONCLUSION

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. These results suggest that AQST-109 represents a safe and effective alternative to injectable epinephrine, which is more portable and needle free.