Data presented at AAAAI/WAO 2025 verify the potential of the epinephrinesublingual film (ESF) Anaphylm for the treatment of type 1 allergic reactions, including anaphylaxis.

A phase III trial (n=64) compared the pharmacokinetics (PK) and pharmacodynamics of the ESF against epinephrine autoinjectors and manual intramuscular epinephrine injection (IM). [AAAAI/WAO 2025, abstract 312]

After one dose, the median T_max variability was shorter with the ESF (12 min) as opposed to the EpiPen (20 min), Auvi-Q (30 min), and the IM (50 min). These suggest that the ESF has a more rapid and consistent PK profile than its comparators, the researchers said.

There were also clinically meaningful and relevant increases in median systolic and diastolic blood pressure in 5 min (>10 mm Hg for both) and heart rate in 8 min (>10 bpm).

Durable under real-world conditions

Another study looked at the durability of ESF under real-world conditions such as water submersion (eg, accidental washing, rain exposure) and folding. [AAAAI/WAO 2025, abstract 304]

After 12 months, the ESF’s potency was 98, 100.7, and 99 percent after being frozen and thawed at 25°C, 40°C, and 60°C, respectively. According to the researchers, these imply that temperature fluctuations only generated minimal change in the film’s potency.

The integrity of the film’s primary pouch was held even after being submerged in 60°C and 25°C water for 30 or 60 min, while a fold endurance test verified its durability under repeated folding.

Freezing and heating did not appear to influence the film, as drug release remained consistent after being subjected to ?80°C, 70°C, and return to room temperature.

“[These suggest that the] ESF demonstrated durability, stability, and performance within specification after exposure to extreme real-world conditions,” said the researchers. “Performance attributes demonstrated that the ESF is the sole epinephrine rescue candidate proven effective under sub-freezing conditions, when other liquid-based formulations would freeze.”

These findings were further supported by another analysis evaluating the ESF for critical quality attributes post-excursion followed by 12 months at ICH* storage conditions. [AAAAI/WAO 2025, abstract 305]

“The post-excursion 12-month stability data reported for the ESF stored at 25°C/60% RH** and 30°C/65% RH, and 6-month stability data reported for 40°C/75% RH comply with acceptance criteria. The potency prior to any exposure was 102.2% LC**,” the researchers said.

After being subjected to 50°C for 28 days, the potency of the ESF was 97.7% LC and 96.9% LC after 12 months at 25°C/60% RH post-excursion.

These effects were sustained after exposure to 60°C for 21 days (97.3% LC and 95.2% LC after 12 months at 25°C/60% RH post-excursion) and 70°C for 7 days (96.6% LC and 91.7% LC after 12 months at 25°C/60% RH post-excursion).

“[These data show] that the ESF maintains stability across a wide range of extreme temperatures, proving robust resilience to environmental stressors. These findings validate the ESF’s reliability in real-world conditions, ensuring sustained efficacy and potency throughout its shelf-life for patients facing life-threatening allergic reactions,” the researchers said.

A saviour in a small package

Epinephrine is the first line of defence against emergency allergic reactions, including anaphylaxis. The investigators across the studies agreed that rescue epinephrine should be small, portable, and withstand real-world environmental conditions without compromising shelf-life.

Collectively, these data suggest that the ESF ? a sublingual film containing a novel prodrug of epinephrine ? does fit the bill, demonstrating potential as a convenient and reliable needle-free alternative in this setting.

“These latest results reinforce the strength of our clinical data and the potential of our product candidate … as a reliable, portable, and effective treatment for anaphylaxis,” said Aquestive CEO Daniel Barber in a news release. “[ESF] was designed to offer patients a more accessible option for emergency epinephrine administration, without the need for an injection or device, if approved by the FDA.”