Popolymer matrix-based sublingual epinephrine continues to show promise: EPIPHAST study

Epinephrine can reach therapeutic plasma concentrations via sublingual administration confirm researchers during the second part of the ongoing EPIPHAST study .

The results were aligned with previous positive results reported for AQST-109, and the product candidate was well tolerated with no serious adverse events.

Aquestive Therapeutics, Inc. (NASDAQ: AQST), has announced positive topline results from Part 2 of the EPIPHAST study for its AQST-109 epinephrine oral film. Utilizing a replicate crossover design, Part 2 confirmed in a larger population of 24 healthy subjects the key pharmacokinetic and pharmacodynamic measures observed in the initial development phases of the EPIPHAST study.

AQST-109 12 mg showed rapid absorption with favorable pharmacokinetics across a variety of key metrics. The median time to maximum concentration (Tmax) was observed to be 15 minutes for AQST-109, compared to 50 minutes for the epinephrine 0.3mg intra-muscular (IM) injection. The Area Under the Curve (AUC) within the clinically relevant periods of 10 minutes, 20 minutes, and 30 minutes, were comparable for both AQST-109 and the 0.3mg IM injection. The median time to reach 100 pg/mL, which has been suggested to be the threshold for the onset of hemodynamic effects, was 8 minutes for AQST-109 and 10 minutes for the 0.3mg IM injection. Part 2 also demonstrated maximum concentration (Cmax) values that were consistent with the 0.3mg IM Injection as well as those previously reported for approved injectable epinephrine devices such as EpiPen®.

Geometric Mean

In addition to positive pharmacokinetic results, AQST-109 demonstrated favorable pharmacodynamic effects on systolic blood pressure, diastolic blood pressure, and heart rate. Consistent with the rapid pharmacokinetic absorption and time to suggested hemodynamically relevant concentration levels (100pg/mL), AQST-109 demonstrated strong and predictable pharmacodynamics across all measured parameters.

"The positive results we are reporting today demonstrate the continued performance of AQST-109, the first and only orally delivered epinephrine product candidate, which represents, if approved by the FDA, a potential paradigm shift in the management of severe allergies, including anaphylaxis. We again showed pharmacokinetic results for AQST-109 that demonstrate delivery of epinephrine with the speed and absorption necessary for a rescue product," said Keith Kendall, Chief Executive Officer of Aquestive. "With so many patients not benefiting from a rescue medicine due to a variety of reasons, from needle phobia to delayed administration, an epinephrine oral film like AQST-109 would provide patients with a rescue medication where they need it, when they need it, and in a form they prefer."

"Patients have had limited treatment options to address anaphylaxis, a disease state that has suffered from a lack of innovation for decades. These promising results, coupled with the convenience of AQST-109 oral administration, underscore the potential to improve upon the current standard of care," said John Oppenheimer, M.D., FAAAAI, Clinical Professor of Medicine at UMDNJ Rutgers, Pulmonary and Allergy Associates NJ. "I look forward to further evaluation of this investigational medicine in the next phase of the EPIPHAST study."

EPIPHAST is a randomized, open-label, three-part adaptive design, crossover study in healthy adult subjects comparing the pharmacokinetics and pharmacodynamics of epinephrine delivered via Aquestive's AQST-109 oral film compared to intramuscular injection of epinephrine. The study is being conducted pursuant to clearance from Health Canada. Part 2 of the EPIPHAST study was a replicate design crossover study in twenty-four (24) healthy subjects comparing the pharmacokinetic and pharmacodynamic measures of AQST-109 12 mg and epinephrine intramuscular injection 0.3 mg.

Aquestive plans to commence Part 3 of the EPIPHAST study in April 2022 and expects to complete the EPIPHAST study by the end of the second quarter of 2022. The purpose of Part 3 is to continue to study the administration of the film under a variety of conditions and further characterize its pharmacokinetics, pharmacodynamics, and safety.

Aquestive received a written response from the U.S. Food and Drug Administration (FDA) in December 2021 to its Pre-Investigational New Drug Application (IND) meeting submission confirming that the development of AQST-109 for the treatment of anaphylaxis under the 505(b)(2) approval pathway is acceptable. Aquestive opened the IND for AQST-109 after receiving FDA clearance in February 2022. AQST-109 met the regulatory criteria for Fast Track designation as announced in March 2022. The Company anticipates conducting an end of Phase 2 meeting with the FDA and commencing the pivotal PK study in the second half of 2022.