LOUISVILLE, Ky. — A sublingual film may be able to deliver epinephrine as effectively as intramuscular injections and provide an alternate pathway for urgent treatment of allergic anaphylaxis, a researcher suggested here.
In testing with healthy volunteers, the sublingual film loaded with AQST-109, which delivers 12 mg of epinephrine, appeared to have similar pharmacokinetics as 0.3 mg epinephrine delivered through injections, reported John Oppenheimer, MD, of the University of Medicine and Dentistry of New Jersey/Rutgers University.
AQST-109 (12 mg) rapidly reached clinically meaningful blood concentrations, he said in his oral presentation at the American College of Allergy, Asthma & Immunology (ACAAI) annual meeting.
Mean maximum observed concentration (Cmax) values was 268 pg/ml with AQST-109 (versus 351 pg/ml with 0.3 mg epinephrine injection) and the time to reach maximum concentration in serum (Tmax) was 22.5 minutes (versus 50 minutes).
The so-called EPIPHAST study was designed to be a randomized, open-label, three-part adaptive design, crossover study in healthy adult subjects. Five oral formulations were determined through phase I testing (16 volunteers in each group).
These oral formulations “can deliver sufficient blood concentrations of epinephrine sooner than that observed with the higher dose of intramuscular epinephrine injection, in line with existing epinephrine autoinjectors,” said Oppenheimer.
“The adverse event profiles and tolerability were similar across all formulations and dosage strengths,” he said. “There have been no concerning safety/tolerability clinical events related to the magnitude of the changes in vital signs.”
He explained that there were increases in systolic blood pressure and heart rate when the sublingual film was administered, but those increases were transient and consistent to what is seen when patients use epinephrine injections.
AQST-109 is being developed because intramuscular injection devices have “certain pitfalls,” Oppenheimer said, including the “lack of auto-injector availability, inadequate education of patients or providers, failure to administer in a timely fashion, and the risk of accidental administration.”
The oral formulation “is easily administered, and the safety and tolerability data demonstrate a favorable safety profile,” he noted.
“Use of a sublingual film could potentially be a game-changer,” session moderator and ACAAI program chair Brian Kelly, MD, of Midwest Allergy and Asthma Center in Omaha, Nebraska, told MedPage Today.
He noted that the research represented early days in the development, but that there was great interest in it. “There are a lot of data out there that look at parental anxiety about giving epinephrine auto-injectors using needles,” he said. “To potentially have a therapy that doesn’t require a needle is very exciting.”
He noted that a nasal epinephrine device is under review at FDA and should be available next year. “A sublingual film would also be very exciting,” he said.
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Disclosures
The study was funded by Aquestive Therapeutics.
Oppenheimer disclosed being on a scientific advisory board for Aquestive Therapeutics.