Sublingual epinephrine film beats syringes, autoinjectors in time to maximum concentration
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Key takeaways:
- The AQST-109 sublingual film provides needle-free delivery of epinephrine.
- AQST-109 achieved faster time to maximum concentration than syringe or autoinjector delivery of epinephrine.
SAN ANTONIO — The pharmacokinetic and pharmacodynamic performance of sublingual epinephrine was comparable to other delivery methods, according to data presented at the American Academy of Allergy, Asthma & Immunology Annual Meeting.
“Epinephrine is the gold standard treatment for anaphylaxis, and prompt administration in a prehospital setting is associated with both lower risk for hospitalizations as well as fatality,” Matthew Greenhawt, MD, MBA, MSc, director of the food challenge and research unit at Children’s Hospital Colorado, said during his presentation.
Epinephrine typically is delivered via injection with a syringe or an autoinjector. However, a PharmFilm technology called DESF delivers the AQST-109 (Aquestive Therapeutics) epinephrine prodrug during anaphylaxis via a sublingual film that dissolves in saliva.
“AQST may actually represent a substantial treatment advancement for patients at risk for anaphylaxis because it can be more readily carried than a device-based epinephrine product,” Greenhawt said.
“This postage stamp-sized product can be carried in a wallet, your pocket or in a small purse — places that are a little bit harder for an autoinjector to fit,” he continued, also emphasizing its needle-free delivery.
The EPIPHASE II phase 1, multi-period, open-label crossover study involved 24 healthy adults (13 women; mean age, 35 years; age range, 24-49 years; 33% white). Each participant received a 12 mg dose of AQST-109, a 0.3 mg dose of epinephrine delivered intramuscularly with a syringe, and a 0.3 mg dose delivered intramuscularly with an autoinjector (EpiPen, Pfizer).
The researchers took pharmacokinetic and pharmacodynamic measurements via plasma samples before each dose and then frequently after each dose for up to 8 hours.
The EpiPen produced a higher maximum concentration (Cmax) of epinephrine (744.2 pg/mL) than AQST-109 (294 pg/mL) and the syringe (411.2 pg/mL). However, AQST-109 had a shorter time to Cmax (Tmax; 12 minutes) than the EpiPen (23 minutes) and the syringe (45 minutes).
“When looking at the area under the curve [AUC] values, the AQST-109 film fell between higher AUC for the EpiPen device and lower AUC for the manual injection when measured over a critical period of up to 30 minutes,” Greenhawt noted.
The researchers also said they observed early and robust increases in systolic and diastolic blood pressure, as well as in pulse, with AQST-109, reflecting faster Tmax compared with the syringe and EpiPen.
Systolic and diastolic blood pressure response, which the researchers called critical to stabilizing patients with anaphylaxis, were strongest with AQST-109 in the first few minutes after administration despite the higher Cmax that EpiPen achieved.
“In terms of safety and tolerability, most adverse events were consistent with the known physiologic effects of epinephrine across the treatments,” Greenhawt said.
No significant treatment-emergent adverse events, categorized as grade 3, were reported. The treatment-emergent adverse events that were reported were mild and categorized as grade 1. They also were transient and resolved with minimal intervention.
“The results here add to the body of evidence indicating that AQST-109 shows promise as a viable, noninvasive and easy-to-carry alternative to device-based epinephrine delivery products for the treatment of anaphylaxis,” Greenhawt said.