(91) Epinephrine delivered via sublingual film (Anaphylm) elicits rapid and consistent pharmacokinetic and pharmacodynamic responses

Background: : Epinephrine is the first-line treatment for severe allergic reactions, including anaphylaxis. Prompt, reliable treatment is critical for patient outcomes. Anaphylm is a sublingual film containing a novel prodrug of epinephrine in development for the treatment of Type I allergic reactions, including anaphylaxis.

Objective: : To evaluate and compare the pharmacokinetics (PK) of epinephrine following a single administration of Anaphylm versus FDA-approved epinephrine products in healthy adult subjects, with the goal of demonstrating that Anaphylm achieves PK parameters within a targeted range – "bracketed" by auto-injectors and manual IM injection.

Methods: : A phase 3 cross-over trial (AQ109301) was conducted in 64 healthy adults evaluating the pharmacokinetics (PK, including time to peak plasma concentration [Tmax]) and pharmacodynamics (PD, heart rate [HR], systolic [SBP] and diastolic blood pressure [DBP]) of Anaphylm compared to epinephrine autoinjectors (EAI) and manual intramuscular epinephrine injection (IM).

Results: : After single dose administration, the Tmax variability as reflected by interquartile range (IQR) was 5.0 minutes (min) for Anaphylm (median Tmax 12 min), 23.5 min for EpiPen (median Tmax 20 min), 32.0 min for Auvi-Q (median Tmax 30 min), and 15.0 min for manual IM injection (median Tmax 50 min). After Anaphylm administration, clinically meaningful changes in median SBP, DBP, and HR were seen in 5 minutes (>10mmHg), 5 minutes (>10mmHg), and 8 minutes (>10bpm), respectively.

Conclusions: : Anaphylm data demonstrates a more rapid and consistent PK profile in comparison to EAIs and IM. Moreover, Anaphylm’s PD profile showed clinically relevant increases in SBP, DBP, and HR. These results further support the development of sublingual epinephrine film as a reliable device-free, needle-free alternative for the treatment of Type I allergic reactions, including anaphylaxis.

Sponsorship:: This study was funded by Aquestive Therapeutics, Inc.