A dissolving epinephrine film for treating allergic reactions retains most of its potency for long periods in the heat. Research also now finds that the film retains much of its potency after being frozen, submerged in water, and repeatedly folded.
The under-the-tongue epinephrine film, developed by Aquestive Therapeutics, was tested for durability in simulated real-world scenarios. The aim was to mimic conditions the film might be placed in when patients carry it in their wallet, phone case or pocket, says Daniel Barber, Aquestive’s president and CEO.
In an extreme heat test, researchers exposed the film to 158 degree Fahrenheit for a week – similar to conditions in a hot car. The film retained 97 percent of its potency after one week and 92 percent after one year.
“This product is very robust for real-world conditions,” says Daniel Barber, Aquestive’s president and CEO. “Based on the parameters we’ve created, you could put it in the washing machine and dryer.”
Aquestive Applies for FDA Approval
A final pediatric clinical trial of the sublingual film, called Anaphylm, in children ages 7 to 17 will wrap up in the coming weeks, Barber said. Update: That trial did wrap up. Then in late March 2025, Aquestive made its submission to the Food and Drug Administration, seeking approval.
If approved, Anaphylm would become the second needle-free alternative for treating serious allergic reactions. The first was neffy, the nasal epinephrine sprayer approved in 2024.
“We feel very good about the filing,” Barber says. “We don’t see any reason why the FDA would come to a different conclusion than the drug is safe and effective and ready to be used by patients.”
Temperature and Epinephrine Carrying
Physicians recommend patients at risk of anaphylaxis carry two auto-injectors at all times. Yet studies show many adults and parents of children with severe allergies don’t always carry auto-injectors.
One challenge in carrying auto-injectors is that they must be stored roughly at room temperature, between 68 and 77 degrees Fahrenheit. Short periods at higher temperatures of up to 86 degrees is permitted.
Prolonged exposure to high temperatures can degrade epinephrine in auto-injectors and potentially make it less effective.
“Most people don’t live their lives in 68 to 77 degrees, 100 percent of the time,” Barber says.
Neffy’s label also recommends storage at room temperature, but allows temperatures of up to 122 degrees for a few days.
Barber says other benefits of Anaphylm are that it’s about the size of a postage stamp, enclosed in a slim foil wrapper that can be easily slipped into a phone case, pocket or wallet. The film dissolves on contact with the membranes under the tongue. No water or swallowing is needed.
“The easier you make it, the lower the barriers to carrying, and the more likely it is someone will actually carry it,” Barber says.
Under-Tongue Film in High Heat, Cold
Aquestive’s heat tolerance testing found that after one year in 122 degrees F heat, the film retained 97 percent of its potency. After one year at 140 F degrees, Anaphylm retained 95 percent of its potency.
The medication even withstood more extreme temperatures, retaining 97 percent of its potency after one week at 158 degrees and 92 percent after one year.
Researchers also tested Anaphylm’s potency after freezing and thawing, soaking in water, repeated folding, and being taken out of the package but not used right away.
Freezing and thawing had little to no effect on Anaphylm’s potency. Auto-injectors have also been shown to hold up in cold temperatures and after freezing. When thawed, auto-injector devices are also likely to still work, studies show.
When soaked in water, the study showed the foil packet remains watertight. Anaphylm retained potency after one hour in 140-degree water, and one week in 77-degree water.
In other tests, they also folded the film repeatedly over the course of a year and found the package remained intact and there was no impact on potency. This test was meant to simulate what might happen to Anaphylm if kept in a back pocket or tossed around inside a purse.
The film also retained nearly 96 percent of its potency after being removed from its package for 12 hours.
These tests show Anaphylm allows “wiggle room for living your regular life,” Barber says.
Aquestive’s FDA Filing
Aquestive’s FDA application includes its pivotal, Phase 3 clinical trial. It involved 64 adults and showed that the dissolving film’s time to reach peak concentration of epinephrine in the blood averaged 12 minutes. That was faster than the EpiPen at 20 minutes, AUVI-Q auto-injector at 30 minutes, and epinephrine given by syringe at 50 minutes.
For safety and ethical reasons, epinephrine studies aren’t done in patients experiencing anaphylaxis. However, the FDA wanted to ensure that the film worked in patients with mouth swelling, which can occur during anaphylaxis.
So the company conducted a study in patients with oral allergy syndrome. That allergic condition leads to localized itching and swelling in the mouth and throat when eating certain raw fruits or vegetables. Anaphylaxis, by comparison, is a full-body response, which often includes oral symptoms.
The oral allergy syndrome study found patients with mouth swelling saw their symptoms ease in two minutes, and completely resolve in 10 minutes. For all patients in the study, the average time to symptom resolution was about 5 minutes.
Anaphylm reached maximum concentration in the blood in 12 minutes on average in people having OAS symptoms. It took 13 minutes to reach peak concentration for those without OAS, and 50 minutes for epinephrine with a syringe.
What’s Next for Anaphylm?
The FDA has 10 months to review a new drug application. A decision on Anaphylm is expected no later than February 2026. If approved, Aquestive will be ready to launch the epinephrine film shortly thereafter.
Anaphylm, which has a 12-milligram dose of epinephrine, would be for adults and children weighing 66 pounds and more.
“We have had consistent communication with the FDA. We believe we have done everything they have asked,” Barber says, including almost 1,000 administrations of the drug in clinical trials.
Article updated: April 2025.
Related Reading:
Epinephrine Film Offers Oral Allergy Relief in Few Minutes: Study
Neffy Epi Spray Halted Anaphylaxis in Kids
