Patients with severe allergies, including those with systemic mastocytosis (SM), will have to wait longer for access to dibutepinephrine (Anaphylm), a needle-free epinephrine treatment, after the U.S. Food and Drug Administration issued a Complete Response Letter requesting changes before approval, according to a press release published recently by the manufacturer, Aquestive Therapeutics.
The FDA’s decision does not challenge whether dibutepinephrine works or is safe but instead highlights concerns about how patients would handle and use the medication during a medical emergency.
Dibutepinephrine is a sublingual film designed to treat life-threatening allergic reactions, including anaphylaxis, in patients weighing 30 kg (about 66 pounds) or more. The film dissolves under the tongue and does not require water, swallowing or an injection. Its small, lightweight packaging is intended to make epinephrine easier to carry, which is especially important for people with SM who face unpredictable and potentially severe anaphylactic episodes related to mast cell activation.
The FDA’s concerns stem from human factors studies that examine real-world use. In these studies, some participants had difficulty opening the pouch or placing the film correctly. In an anaphylactic emergency, even small delays or mistakes could increase risk. Because of planned changes to packaging and instructions, the FDA also requested a single pharmacokinetics study to confirm that these updates do not alter how the drug is absorbed in the body.
“We remain confident in the effectiveness and safety of Anaphylm and its potential as an easy-to-use, easy-to-carry, fast-acting epinephrine treatment,” said Daniel Barber, President and CEO of Aquestive.
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Aquestive Therapeutics said it has already modified the pouch design, instructions for use and labeling to address the FDA’s feedback. The company plans to conduct a new human factors validation study alongside the requested pharmacokinetics study. Importantly for patients, the FDA did not raise concerns about manufacturing quality or the drug’s overall development data.
For patients, this decision means dibutepinephrine will not yet be available in the United States. However, the delay is considered procedural rather than a rejection of the therapy itself. Based on current plans, the company expects to resubmit its application as early as the third quarter of 2026 and will seek a rapid FDA review.
Outside the U.S., progress continues. European regulators have indicated that no additional clinical trials are required before submission, and applications in Europe and Canada are planned for the second half of 2026. If ultimately approved, dibutepinephrine could expand treatment options for patients with SM and others at risk of anaphylaxis by offering a noninvasive alternative that may be easier to carry and use in urgent situations.
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