▎WuXi AppTec Content Team Editor
Aquestive Therapeutics recently announced positive top-line results from the EPIPHAST II trial of its epinephrine sublingual film AQST-109. The results showed that the median time to maximum plasma drug concentration (Tmax) of AQST-109 was significantly faster compared to epinephrine auto-injector and ordinary intramuscular injection of epinephrine, and repeated dosing provided plasma concentrations significantly higher.
Anaphylaxis is a severe systemic hypersensitivity reaction that occurs rapidly and can be fatal in severe cases. The most common causes of allergic reactions are foods (such as peanuts), venom from insect bites, and medicines. In the event of an anaphylaxis, it is extremely important to deliver systemic epinephrine more rapidly to stop the anaphylaxis early and prevent its progression, as any delay may result in severe bronchospasm, acute respiratory and/or cardiovascular failure, or even die.
AQST-109 is a polymer matrix-based epinephrine prodrug in a sublingual film for rapid sublingual delivery of epinephrine. The product is about the size of a postage stamp, requires no water or swallowing, and dissolves when placed under the tongue. The packaging of the AQST-109 is thinner and smaller than regular credit cards, making it easy to carry and can withstand weather changes such as exposure to rain and/or sunlight.
In the EPIPHAST II trial, the Tmax of a single dose of AQST-109 was compared with a 0.3 mg epinephrine auto-injector, regular intramuscular injection of 0.3 mg epinephrine, and repeated doses of AQST-109 and the mean maximum plasma concentration (Cmax) of 0.3 mg of epinephrine injected intramuscularly. The results showed that the mean time to Tmax was significantly faster with a single dose of AQST-109 at 12 minutes, the mean time to Tmax with epinephrine auto-injector was 22.5 minutes, and the mean time to Tmax with regular intramuscular injection was 45 minutes . Repeated administration of AQST-109 resulted in significantly higher plasma concentrations, a Tmax of 8 minutes after administration, and extensive absorption was observed. The mean Cmax of AQST-109 was 465 pg/mL after one dose and 2958 pg/mL after two doses. In contrast, intramuscular injection of 0.3 mg epinephrine resulted in a Cmax of 489 pg/mL after one dose and 911 pg/mL after two doses. The Cmax after a single dose of the epinephrine auto-injector was 869 pg/mL.
Furthermore, changes in systolic blood pressure and heart rate following single-dose AQST-109 and single-dose epinephrine auto-injectors were similar. After patients received a dose of AQST-109, the greatest mean effect on systolic blood pressure occurred within 5 minutes of administration, compared with 8 minutes for epinephrine auto-injector; the greatest mean effect of AQST-109 on heart rate occurred within 5 minutes of administration. Within 8 minutes after dosing, compared to 5 minutes for epinephrine auto-injector. The safety results of AQST-109 were as expected, with no serious adverse events reported.
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