Sublingual Epinephrine Film Shows Comparable Safety and Efficacy in Pediatric Patients
Key Insights
A phase 1 study of 32 pediatric patients aged 7-17 years demonstrated that Anaphylm sublingual epinephrine film achieved pharmacokinetic and pharmacodynamic profiles comparable to those previously observed in adults.
The sublingual film produced a maximum epinephrine concentration of 568.6 pg/mL in children compared to 470.2 pg/mL in adults, with faster time to peak concentration (10 minutes vs 12 minutes).
Treatment-emergent adverse events occurred in 84.4% of pediatric participants but were predominantly mild and self-resolving, with safety profiles consistent with adult populations.
A phase 1 study has demonstrated that Anaphylm (AQST-109), a sublingual epinephrine film developed by Aquestive Therapeutics, produces pharmacokinetic and safety profiles in pediatric patients that are comparable to those previously observed in adults. The findings, presented at the American College of Allergy, Asthma & Immunology (search) Annual Scientific Meeting in Orlando, support the potential use of this needle-free delivery system as an alternative to traditional epinephrine auto-injectors for children at risk of anaphylaxis (search).
Study Design and Population
The open-label, single-treatment, multi-site phase 1 study enrolled 32 pediatric patients aged 7 to 17 years (median age 13 years; 62.5% boys) with a history of allergic reactions (search) and at high risk for serious allergic reactions. All participants weighed at least 30 kg (median weight 47.15 kg; median BMI 18.7 kg/m²) and received a single 12 mg dose of Anaphylm to assess pharmacokinetics and pharmacodynamics.
"Anaphylaxis (search) is a very prominent problem," said Matthew Greenhawt, MD, MBA, MSc, chief medical officer of the Asthma and Allergy Foundation of America (search), who presented the study results. "Pediatric risk is estimated to be anywhere from one to 761 per 100,000 person-years."
Pharmacokinetic Results
The pediatric population demonstrated rapid systemic epinephrine absorption following Anaphylm administration. The sublingual film produced a geometric mean maximum concentration (Cmax) of 568.6 pg/mL in children, which "slightly exceeded" the Cmax of 470.2 pg/mL found in a separate study of adults. The median time to Cmax was 10 minutes in pediatric patients, shorter than the median time to Cmax of 12 minutes observed in the adult study.
"Both of those are considerably faster than comparative reference drugs," Greenhawt noted. Cross-study statistical analyses using 2-sample t-tests on natural log transformed values revealed no statistical difference between the adult and pediatric populations.
Pharmacodynamic Effects
Treatment with AQST-109 produced expected cardiovascular responses consistent with epinephrine's known pharmacology. Researchers reported transient rises in systolic blood pressure (mean maximum effect 15.4 mm Hg; median time to maximum effect 11 minutes), diastolic blood pressure (mean maximum effect 9.8 mm Hg; median time to maximum effect 8 minutes), and heart rate (mean maximum effect 12.5 bpm; median time to maximum effect 12 minutes).
"This is exactly what you would expect to see when you give epinephrine: rapid response," Greenhawt explained. He noted that unlike intramuscular epinephrine injection, which sometimes causes a small dip in diastolic pressure before recovery, this pattern was not observed with the sublingual formulation.
Safety Profile
Within the pediatric population, 84.4% of participants reported drug-related treatment-emergent adverse events, though most were mild and self-resolving. Patient-reported events occurring in at least 5% of participants included hypoesthesia (12.5%), paresthesia (12.5%), discomfort (12.5%), nausea (12.5%), vomiting (9.4%), and pain (6.3%). Greenhawt characterized these reactions as local and site-specific.
Clinician-observed oral cavity findings during routine examinations included exfoliation (28.1% of participants), erythema (18.8%), pallor (15.6%), and ulceration (9.4%). However, 57% of these clinician-observed events were asymptomatic, and all but one were either asymptomatic or mild in severity. Only one of the three ulcerative events was mildly symptomatic.
"The safety results were consistent with the adult population," Greenhawt added.
Clinical Significance
Study investigator David Golden, MD, clinical associate professor of medicine at Johns Hopkins University School of Medicine, emphasized the distinction between expected pharmacologic effects and true safety concerns. "If nobody had those side effects, the drug probably wouldn't be working," Golden explained. "Epinephrine is not a dangerous drug. It may make your heart race, it may make you shaky. That just shows that it's working."
The sublingual film formulation offers several practical advantages over traditional auto-injectors. Anaphylm is approximately the size of a US postage stamp and comes in packaging that is thinner and smaller than a credit card. The product weighs less than 1 ounce and is amenable to carrying in a pocket, with packaging resistant to weather excursions including exposure to rain or direct sunlight.
Regulatory Status
The FDA accepted Aquestive Therapeutics' new drug application for Anaphylm sublingual epinephrine film for treating anaphylaxis (search) and other type 1 allergic reactions (search) in June. The Prescription Drug User Fee Act target action date is January 31, 2026.
The investigators noted that research continues to develop an appropriate sublingual dose for children weighing less than 30 kilograms, which could further expand access to the orally administered delivery system. "Sublingual film can rapidly achieve therapeutic epinephrine levels without injection, offering a non-invasive pediatric anaphylaxis (search) management option," the study authors concluded.