Benzinga | Oct 25, 2021 08:33AM EDT

Aquestive Therapeutics Reports Positive Topline Data From Phase 1 Pharmacokinetic Trial Of AQST-109 Supporting Its Development As Oral Alternative To Epinephrine Autoinjectors For Emergency Treatment Of Allergic Reactions

Aquestive Therapeutics, Inc. (NASDAQ:AQST), a pharmaceutical company focused on developing and commercializing differentiated products that address patients' unmet needs and solve therapeutic problems, today announced positive topline data from its first-in-human Phase 1 PK study of AQST-109 sublingual film for the delivery of epinephrine in the emergency treatment of allergic reactions including anaphylaxis. Findings from this study support AQST-109's potential as the first orally administered epinephrine treatment for anaphylaxis, with safety, tolerability, PK and pharmacodynamics (PD) measures that fall within the target range of standard of care autoinjectors such as epinephrine pens which require patients or caregivers to inject into their thighs during an emergency allergic reaction.

"These findings represent a critical step forward in the development of our product candidate AQST-109 as the first oral product aiming to treat anaphylaxis," said Keith Kendall, Chief Executive Officer of Aquestive. "The optimized PK/PD profile of our epinephrine prodrug demonstrates that our oral alternative to epinephrine injection can, in fact, match the PK parameters of autoinjectors while lowering barriers to use and improving convenience, ultimately resulting in better, often life-saving outcomes for patients. Based on our review of published literature, AQST-109 is the only non-injection form of epinephrine to achieve a median Tmax of 15 minutes or less. We are encouraged by these findings and continue to believe patients will embrace this needle-free, user-friendly alternative."

AQST-109 is a polymer matrix-based film that can be applied sublingually (under the tongue) for the rapid delivery of epinephrine. The product is similar in size to a postage stamp and begins to dissolve on contact. No water or swallowing is required for administration. The packaging for AQST-109 is thinner and smaller than an average credit card, can be carried in a pocket, and is designed to withstand weather excursions such as exposure to rain and/or sunlight. Current stability data is tracking favorably to support a two-year shelf life.

The Phase 1 randomized, single-ascending dose (SAD) study was performed with AQST-109 in order to assess safety, tolerability, PK, and PD profiles. The study was conducted in Canada pursuant to a clinical trial application approved by Health Canada. Subjects participating in the trial received, in ascending fashion, sublingually administered doses of AQST-109 across four different formulations. The four formulation compositions were varied to assess critical absorption factors including drug loading and the use of inventive excipients designed to influence absorption, stability, and the conversion of the prodrug. A target formulation ("formulation #2" highlighted below) was designed as the lead candidate for the study.

Study Highlights

* Key clinical measures for comparability to existing autoinjectors (Cmax, Tmax, and area under the curve, or AUC) were within expected ranges for formulations 1, 2 (target), and 4

* Observed PD values were comparable to existing data for autoinjectors

* AQST-109 was generally well tolerated with no serious adverse events

Study Results AQST-109 (epinephrine prodrug Comparable Data from Previous sublingual film) 12 mg & Published StudiesFilm 1 2 (Target) 3 4 EpiPen(R) EpiPen(R) Auvi-Q(R)Formulation # 1 2 1Dosings (n) 6 8 6 7 135 10 67Cmax (pg/mL) 552 762 164 307 518 341 484AUC 0-t (hr&# 634 603 329 303 560 328 526x2A;pg/mL)Median Tmax 15 15 20 10 10 22 20(minutes)Tmax range 15-25 10-35 20-50 5-50 4-60 5-90 5-60(minutes)

This study indicated that AQST-109 was absorbed and rapidly converted to epinephrine with an observed median Tmax of 15 minutes and an observed geometric mean Cmax of 762 pg/mL for the target formulation. The findings for the target formulation are comparable to published study results for both EpiPen and Auvi-Q1234567. In addition, the target formulation had similar median Tmax values at lower dose strengths (15 minutes and 17.5 minutes for the 6 mg and 9 mg doses, respectively, included in the study). Based on the study results, Aquestive plans on continuing development of the target formulation to take forward into a pivotal PK study.

Safety data indicated that AQST-109 was generally well tolerated with no serious adverse events (SAE's), significant medical events, or treatment-related severe adverse events reported within the trial. All treatment-emergent adverse events (TEAEs) deemed at least possibly related were mild to moderate in nature across cohorts.

The PD markers measured changes from baseline in heart rate, systolic blood pressure, and diastolic blood pressure. The changes observed suggest a comparable effect for AQST-109 when compared to autoinjectors in healthy volunteers.

David Fleischer, MD, Section Head, Pediatric Allergy and Immunology at Children's Hospital Colorado, Professor of Pediatrics at University of Colorado School of Medicine, commented, "An epinephrine delivery solution such as AQST-109 for cases of severe life-threatening allergic reactions could address the most important factor contributing to anaphylaxis fatality: the therapeutic time window. The needle-free, pocket-sized, and temperature safe attributes of this first-of-its-kind orally administered prodrug will make it the preferred choice for parents of children facing these risks."

Aquestive has submitted its request for a pre-investigational new drug (IND) meeting with the U.S. Food and Drug Administration (FDA) and anticipates receiving a written response from the FDA before the end of the year. In parallel, Aquestive is on track to conduct a crossover study using an adaptive design for AQST-109 in Canada beginning in the fourth quarter 2021. It is anticipated that this study will establish a final formulation and dose strength for commercial scale-up. The study will include comparisons to 0.3 mg and 0.5 mg epinephrine intramuscular (IM) manual injection and is anticipated to complete in the first half of 2022.

A presentation of the results of the Phase 1 PK study of AQST-109 is available on the events and presentation of the investor section of the Company's website at https://investors.aquestive.com/events-and-presentations# and has been filed with the SEC on Form 8-K.