FDA Issues CRL for Aquestive’s Anaphylm: Resubmission Expected in Q3 2026

Aquestive Therapeutics announced on February 2, 2026, that it received a Complete Response Letter (CRL) from the Food and Drug Administration (FDA) regarding its New Drug Application (NDA) for Anaphylm (dibutepinephrine) Sublingual Film. This therapy is intended for the treatment of type I allergic reactions, including anaphylaxis, in patients weighing at least 30 kg (approximately 66 pounds).

Human Factors at the Core of the Delay

The FDA’s CRL, dated January 30, 2026, does not cite concerns regarding the safety, efficacy, or manufacturing quality of dibutepinephrine. Instead, the agency’s feedback centers on human factors and labeling issues related to how the product is administered. Specifically, the FDA identified difficulties users experienced in studies opening the pouch and correctly placing the sublingual film.

Did You Know? Aquestive initiated regulatory engagements in Canada, Europe, and the United Kingdom in 2025.

Aquestive has already begun addressing these concerns by modifying the pouch opening mechanism, instructions for use, and both pouch and carton labeling. The company plans to conduct a new human factors validation study incorporating these changes and will also evaluate potential tolerability issues. Comparability data previously submitted to the FDA, including bracketing, repeat-dose, and sustainability data, were not questioned in the CRL.

Pharmacokinetics Study Also Requested

In addition to the human factors concerns, the FDA requested a single pharmacokinetics (PK) study to assess the impact of the packaging and labeling changes. The agency indicated that the human factors and PK studies could be conducted concurrently. No further clinical or nonclinical studies were requested.

Expert Insight: The FDA’s focus on usability and patient experience highlights the critical importance of ensuring that life-saving medications can be administered quickly and correctly, particularly during a medical emergency like anaphylaxis.

Aquestive estimates it can resubmit the NDA in the third quarter of 2026, contingent upon the timely completion of the required studies and standard FDA review timelines. The company intends to request a Type A meeting with the FDA to discuss the most efficient path forward and seek rapid review of the resubmission.

Global Outlook Remains Positive

Despite the setback in the US, Aquestive continues to pursue regulatory approval of dibutepinephrine internationally. The company reported receiving positive feedback from the European Medicines Agency (EMA), which indicated that no additional clinical trials would be required prior to submission. Aquestive expects to submit a marketing authorization application in Europe and a New Drug Submission in Canada in the second half of 2026. Feedback from the UK’s Medicines and Healthcare Products Regulatory Agency is anticipated in the first quarter of 2026.

Frequently Asked Questions

What is Anaphylm?

Anaphylm (dibutepinephrine) Sublingual Film is a noninvasive epinephrine therapy being developed for the treatment of type I allergic reactions, including anaphylaxis, in patients weighing at least 30 kg (approximately 66 pounds).

What were the FDA’s specific concerns?

The FDA’s concerns, as outlined in the Complete Response Letter, relate to human factors and labeling issues regarding product administration, specifically difficulties users experienced opening the pouch and correctly placing the sublingual film.

What are Aquestive’s next steps?

Aquestive plans to modify the pouch opening mechanism, instructions for use, and labeling, conduct a new human factors validation study, and complete a single pharmacokinetics study. The company anticipates resubmitting the NDA in the third quarter of 2026.

Given the challenges in administering epinephrine during an allergic reaction, how might improved usability of medication delivery systems impact patient outcomes?