Aquestive Therapeutics, Inc. released positive topline clinical data from its Phase 3 pivotal pharmacokinetic (PK) clinical study of Anaphylm?? (epinephrine) Sublingual Film and findings from the FDA Type C meeting. Anaphylm is the Company?s first and only orally administered epinephrine prodrug product candidate under development for the treatment of severe life-threatening allergic reactions, including anaphylaxis.

Topline Data from Pivotal Phase 3 Study in Adults: The two-part, Phase 3, single-center, open-label, randomized study was designed to compare the PK and pharmacodynamics (PD) of single and repeat doses of Anaphylm versus single and repeat doses of the epinephrine intra-muscular (IM) injection and epinephrine autoinjectors (EpiPen® and Auvi-Q®) in healthy adult subjects. The primary endpoint was to compare the PK of epinephrine following the single administration of Anaphylm to the single administration of Adrenalin (epinephrine IM injection) and autoinjectors in healthy adult subjects. The secondary endpoints included evaluating PK sustainability following repeat administration and the safety and tolerability following single and repeat administrations versus epinephrine IM injection and epinephrine autoinjectors.

The single dose part of the Phase 3 study was designed as a four period, four-treatment, four-sequence, comparative PK study with 64 enrolled adult subjects. As outlined in the presentation posted to the Company?s website and filed with the SEC, key findings from the single dosing part of the study included that Anaphylm: Achieved a geometric mean Cmax of 470 pg/mL bracketed by epinephrine autoinjectors AUVI-Q at 521 pg/mL and EpiPen at 469 pg/mL, Generated partial AUCs between (bracketed) autoinjectors and Adrenalin manual IM injection from 5 to 60 minutes; Maintained a median Tmax of 12 minutes compared to 20 minutes for EpiPen, 30 minutes for AUVI-Q, and 50 minutes for Adrenalin, Produced a meaningful change from baseline pharmacodynamic measures of blood pressure and heart rate at the first tracked time point of 2 minutes, and Was consistently well tolerated with no SAEs. The repeat dosing part of the Phase 3 study was designed as a three-period, three-treatment, six sequence, comparative PK study with 36 enrolled adult subjects.

As outlined in the presentation posted to the website and filed with the SEC, the key findings from the repeat dosing part of the Study included that Anaphylm: Maintains epinephrine plasma concentrations equal to or greater than existing injection products at all but 1 timepoint out to 2 hours, Demonstrated a median Tmax of 10 minutes after administration of the second dose, Exhibited consistent pharmacodynamics, and Was consistently well tolerated with no SAEs. FDA Type C Meeting: The Company also successfully completed a Type C meeting with the FDA that addressed open items from the November 2022 End-of-Phase 2 meeting including addressing (1) the impact of any product hold time, (2) the potential for emesis (vomiting), and (3) the impact of potential mouth conditions such as angioedema (swelling). In response to these questions, the FDA indicated that the Company has ?adequately addressed?

the FDA?s previous concerns by removing product hold time from the administration instructions and provided additional information on how to characterize emesis in the Company?s NDA submission. Regarding mouth conditions, the FDA recommended administering Anaphylm after oral exposure to a known allergen and assessing PK performance thereunder. The Company will execute this study in the second quarter of 2024.

This study will replace the Company?s previously planned angioedema study. The FDA noted that substantial progress had been made in the Anaphylm clinical development program and did not outline any new clinical development requirements. As expected, the FDA reiterated that, as with other epinephrine programs under development, concentrations of epinephrine above known EpiPen levels must be justified from a safety perspective, and PK sustainability remains a focus.

Furthermore, the FDA recommended that Aquestive begin its pediatric study after completion of the remaining adult studies. The Company is aligned with this recommendation from the FDA. The FDA reserved judgement on the sufficiency of the Anaphylm clinical development program until completion of ongoing and planned studies, the results of which are expected to be presented at the pre-NDA meeting.