Anaphylm sublingual film may resolve symptoms of severe allergic reactions including anaphylaxis: OAS challenge study

According to results from Oral Allergy Syndrome (OAS) challenge study, Anaphylm (epinephrine) sublingual film achieved key primary and secondary endpoints for resolving symptoms of severe allergic reactions, such as anaphylaxis. Further Anaphylm showed rapid symptom resolution in severe allergic reactions, with effects starting in 2 minutes and complete resolution by 12 minutes.

Consquently Aquestive Therapeutics plans to submit an NDA for Anaphylm in Q1 2025 based on results.

The OAS challenge study was designed as a two-part investigation to evaluate the PK and pharmacodynamics (PD) of Anaphylm in adults with allergen-induced oral physiological change. Part 1 of the study enrolled subjects with confirmed OAS into a three-period study with the following arms: (1) Anaphylm with allergen exposure (n=18 single dose; n=18 repeat dose); (2) Anaphylm without allergen exposure (n=15 single dose; n=13 repeat dose); and (3) Adrenalin intramuscular (IM) injection without allergen exposure (n=18 single dose; n=17 repeat dose). Part 2 was an optional follow-on study to Part 1. Six subjects who received single dose in Part 1 received repeat dose; and six subjects who received repeat dose in Part 1 received single dose. Anaphylm was administered with allergen exposure, while IM was administered without allergen exposure. During allergen exposure arms in Parts 1 and 2, subjects were exposed to a fruit they were known to be allergic to, and the resulting symptoms were documented for location, severity, and duration. There were no reports of difficulty administering Anaphylm to subjects in the study.

Following allergen exposure, all subjects reported symptoms consistent with those experienced with their known allergies. Approximately twenty-five percent of subjects reported swelling of their tongues, lips, cheeks, and/or throat. Additional mucosal allergic symptoms included tingling, pain, and nasal congestion. Ninety-four percent of subjects were categorized as having moderate or severe symptoms according to the pre-defined oral severity score.

The median time for complete symptom resolution for subjects in the study following administration of Anaphylm was twelve minutes. This is faster than the median time to complete symptom resolution at screening, which was seventy-four minutes. After Anaphylm administration, symptoms began resolving as early as two minutes in some subjects and fifty percent of all symptoms across all subjects were resolved by five minutes. Importantly, all instances of symptomatic swelling were completely resolved by five minutes after administration of Anaphylm.

Both primary and secondary endpoints of the OAS challenge study were successfully met with no significant differences found between Anaphylm PK results in subjects with and without allergen exposure. Anaphylm PK results in subjects with allergen exposure remained similar to previous profiles from the Company’s pivotal study in healthy subjects. The time to maximum plasma concentration, or Tmax, remained at twelve minutes in subjects with and without allergen exposure following a single dose of Anaphylm. The maximum plasma concentration, or Cmax, was comparable between Anaphylm administered with and without allergen exposure. In addition, Anaphylm was safe and well-tolerated with all adverse events categorized as mild or moderate and resolving without medical intervention.

“Symptom relief is the most real-world scenario whereby subjects know their rescue product is working,” said Jay Lieberman, M.D., Professor at the University of Tennessee Health Science Center, physician at LeBonheur Children’s Hospital, and Chair of the Annual Meeting Program for the American College of Allergy, Asthma, and Immunology (ACAAI). “I am reassured by the speed of symptom relief seen in the OAS Study and by the continued and consistent rapid absorption profile of Anaphylm. These data provide strong evidence that Anaphylm could provide a reliable alternative to the approved epinephrine medical devices currently available to patients.”

"We are extremely pleased with the positive results from our OAS challenge study, which further validate Anaphylm's potential as a game-changing treatment option for severe allergic reactions, including anaphylaxis, if approved by the FDA" said Daniel Barber, President and Chief Executive Officer of Aquestive. "These results demonstrate that Anaphylm maintains its consistent PK and PD profile even when administered during oral allergic conditions, such as swelling. In addition, Anaphylm demonstrated its ability to resolve symptoms following the introduction of an oral allergen. This is a critical finding as we advance towards our NDA submission, as it confirms Anaphylm's potential effectiveness in real-world allergic scenarios."

Aquestive has requested a pre-NDA meeting with the FDA and expects to meet with the FDA in the fourth quarter of 2024. The Company remains on track to commence a pediatric study in subjects weighing 30 kgs and above in the fourth quarter 2024 and to submit a New Drug Application (NDA) to the FDA in the first quarter 2025. If approved by the FDA, Aquestive is poised to initiate a full product launch of Anaphylm in the first quarter of 2026.

About Anaphylm™ (epinephrine) Sublingual Film

Anaphylm™ (epinephrine) Sublingual Film is a polymer matrix-based epinephrine prodrug product candidate. Anaphylm is similar in size to a postage stamp, weighs less than an ounce, and begins to dissolve on contact. No water or swallowing is required for administration. The packaging for Anaphylm is thinner and smaller than an average credit card, can be carried in a pocket, and is designed to withstand weather excursions such as exposure to rain and/or sunlight. The Anaphylm trade name for AQST-109 has been conditionally approved by the FDA. Final approval of the Anaphylm proprietary name is conditioned on FDA approval of the product candidate.