Sublingual epinephrine film demonstrates potency, durability in real-world conditions
Key takeaways:
- Testing included extreme temperatures, submersion in water, and repeated folding.
- Strips retained potency after exposures to a range of temperatures for varied lengths of time.
SAN DIEGO — Aquestive Therapeutics’ Anaphylm AQST-109 epinephrine sublingual film demonstrated durability despite testing in extreme temperatures and other environmental conditions, according to a pair of posters presented here.
Testing represented what the film may encounter as patients carry it in the real world, Steve Wargacki, PhD, chief science officer, Aquestive Therapeutics, said at the 2025 American Academy of Allergy, Asthma & Immunology/World Allergy Organization Joint Congress.
“Testing under real-world conditions is essential because emergency medications need to work reliably within the complexity of patients’ everyday lives,” Wargacki told Healio. “People with severe allergies do not live their lives in laboratory environments.”
For example, the researchers said, Anaphylm could wind up in the refrigerator or the washing machine, or it could be left in a hot car, exposed to rain, subjected to folding, or prematurely removed from its packaging.
Wargacki also called conventional epinephrine autoinjectors bulky and noted that they must be stored between 68°F and 77°F, creating practical challenges for many patients.
“Research shows many patients at risk of anaphylaxis do not consistently carry their autoinjectors, with size, bulk and temperature sensitivity being among the barriers they face,” he continued.
The company’s testing subjected Anaphylm to scenarios that mirror everyday situations, Wargacki said, including prolonged heat exposure, freezing and thawing, water submersion, folding and extended exposure.
“These tests are not academic exercises,” he said. “These tests were designed to simulate real challenges patients face.”
First, the company froze replicate sample sets of Anaphylm at –20°C for 24 hours and thawed it at 25°C ± 2°C, 40°C ± 2°C, and 60°C ± 2°C, repeating this cycle three times, before storing them at 25°C and 60% relative humidity and testing them at 3, 6, 9 and 12 months.
Compared with samples that were not frozen, these samples retained their potency for up to 12 months, including 98% potency for the 25°C thaw group, 100.7% for the 40°C thaw group and 99% for the 60°C thaw group.
“Potency is the amount of active ingredient that remains in the drug product available for absorption,” Wargacki said. “All pharmaceutical products must ensure potency throughout their shelf life, and this is assessed through a validated assay method — in this case, using high-performance liquid chromatography.”
Next, the researchers put Anaphylm samples in sealed pouches and submerged them in water that was 60°C for 30 and 60 minutes before storing them for 24 hours at 25°C and 60% relative humidity and submerging them in water that was 25°C for 1 day and 7 days, followed by testing.
The researchers reported that the impact of this submersion on dissolution rates was minimal, indicating that Anaphylm was usable under these conditions.
“Dissolution is a characterization of how the drug is released from product matrix — in this case, the film,” Wargacki said. “Even when the film is frozen or at an extremely elevated temperature, if it was used at those conditions, it works the same as when the product is at room temperature.”
Further, the researchers removed Anaphylm strips from their packages and stored them in a 25°C environment with 60% relative humidity, retaining 98.1% potency at 3 hours, 100% potency at 6 hours, 97% potency at 9 hours and 95.6% potency at 12 hours.
Anaphylm also was exposed to 50°C for 28 days, retaining 97.7% potency; 60°C for 21 days, retaining 97.3% potency; and 70°C for 7 days, retaining 96.6%.
After 12 months of storage in a 25°C environment with 60% relative humidity, the 50°C set retained 96.9% potency, the 60°C set retained 95.2% potency and the 70°C set retained 91.7% potency.
Also, the 60°C and 70°C sets released at least 80% of their epinephrine within 10 minutes of administration, and the 50°C set released 80% of its epinephrine within 15 minutes.
Repeated folding at 180° for 12 months did not impact the strips’ physical integrity or potency as well, the researchers added, including strips that were frozen and thawed and strips that were stored up to 28, 21 and 7 days at 50°C, 60°C and 70°C with 60% relative humidity.
“This is a standard 180° fold test,” Wargacki said. “It was done manually but under the same procedure as automated test methods.”
Finally, strips that were subjected to –80°C and –20°C temperatures released at least 80% of their epinephrine within 7 minutes, and strips subjected to 70°C released at least 80% of their epinephrine within 10 minutes.
Noting that Anaphylm is the only epinephrine candidate that has demonstrated that it is effective in subfreezing temperatures, the researchers said these findings indicate Anaphylm’s durability across a range of temperatures and conditions that patients may encounter in real life.
“The testing results demonstrate Anaphylm’s remarkable stability: 92% potency retention after a week at 158°F and a year of long-term storage, consistent performance after water exposure, freezing and repeated folding,” Wargacki said.
“This stability profile has the potential to transform how patients manage their condition by providing a peerless flexibility that matches their lifestyles,” he continued. “For a medication that should be carried at all times and work in an emergency, real-world durability testing is essential.”
Aquestive Therapeutics has begun the filing process with the FDA for Anaphylm’s approval.
“We expect to complete this application process over the next several weeks and expect the next major milestone for this program, the acceptance of the NDA by the FDA, sometime in June,” Wargacki said. “This expected timeline would put us on track to launch Anaphylm on schedule in the first quarter of 2026, if Anaphylm is approved by the FDA.”