FDA Rejects Aquestive's Oral Anaphylaxis Treatment, Leaving Patients Awaiting Epinephrine Alternative
February 2, 2024 — The U.S. Food and Drug Administration (FDA) has declined to approve Aquestive Therapeutics' experimental oral treatment for severe allergic reactions, dealing a setback to the company's bid to offer an alternative to traditional epinephrine injectors like EpiPens.
The agency issued a Complete Response Letter (CRL) for Aquestive's New Drug Application (NDA) for AQST-109, a sublingual film formulated with epinephrine. The company disclosed the regulatory decision in a statement on Monday but did not specify the FDA's concerns, stating only that it would request a meeting with the agency to discuss the path forward.
AQST-109 was positioned as a potential game-changer for the estimated millions of Americans with life-threatening allergies. The dissolvable film, placed under the tongue, aimed to provide a needle-free, portable, and potentially easier-to-administer option during anaphylactic emergencies. The current standard of care relies on auto-injectors, which some patients and caregivers find intimidating or cumbersome.
"This decision underscores the high regulatory bar for any product intended for use in emergency, life-or-death situations," said Dr. Evelyn Reed, an allergist at Boston Medical Center who was not involved in the trial. "While the need for user-friendly options is clear, the FDA must be unequivocally confident in the drug's rapid and reliable absorption and efficacy under real-world, stressful conditions."
The rejection is a significant blow to Aquestive, which has invested heavily in its PharmFilm® technology platform. The company's stock fell sharply following the announcement. Analysts suggest the FDA's concerns likely revolve around pharmacokinetic data—how quickly and completely the body absorbs the drug compared to an intramuscular injection—or manufacturing controls.
Expert Commentary & Reaction
We asked for reactions from individuals connected to the allergy community:
Michael Torres, Father of a child with peanut allergies (New Jersey): "This is incredibly disappointing. We carry an EpiPen everywhere, and the anxiety of having to use a needle on my panicking child is a constant weight. We were really hoping this oral option would come through. The FDA's caution is understandable, but it feels like the goalposts keep moving for families like mine who just want a reliable, less traumatic choice."
Dr. Sarah Chen, Immunologist and Researcher (Stanford University): "The science behind non-injectable epinephrine is challenging. The mucosal absorption in the mouth must be rapid and consistent enough to match the gold-standard injection, especially when a patient's blood pressure is crashing. The CRL is not the end of the road; it's the FDA asking for more robust data. This is how the process is supposed to work to ensure patient safety."
Linda Briggs, Patient Advocate & Blogger ('Allergy Life'): "Frankly, I'm furious. This feels like bureaucracy over lived experience. Auto-injectors are expensive, bulky, and people freeze when they have to use them. An oral film could save lives by increasing the likelihood that treatment is actually administered. The FDA is prioritizing perfect data over a practical solution that addresses very real human factors in an emergency."
David Park, Pharmaceutical Industry Analyst (Greenleaf Capital): "This was a high-risk, high-reward application for Aquestive. The commercial opportunity in the anaphylaxis market is substantial, but so are the regulatory hurdles. The CRL will require additional investment and time, extending their runway to market and giving competitors with similar oral or intranasal products a chance to catch up."
The path forward for AQST-109 remains uncertain pending discussions with the FDA. The decision also casts a shadow on other companies developing non-injectable epinephrine products, highlighting the stringent efficacy requirements for this critical drug class.