On Monday, Aquestive Therapeutics, Inc. (NASDAQ:AQST) received a Complete Response Letter (CRL) from the U.S. Food and Drug Administration (FDA) for the New Drug Application (NDA) seeking approval of Anaphylm (dibutepinephrine) Sublingual Film for Type I allergic reactions, including anaphylaxis, in patients weighing 30kg or more (approximately 66 pounds).  

In January, the FDA identified deficiencies in Anaphylm's NDA that preclude discussion of labeling and post-marketing commitments at this time.

“While it is unfortunate to have received a CRL…We are encouraged that the issues in the letter are limited to human factors and a supportive PK study, once human factors are addressed, and we noted several labeling comments that will inform the final label for Anaphylm, if approved by the FDA,” said Daniel Barber, President and CEO of Aquestive.

In the CRL, which focuses on administration and labeling guidance, the FDA cited deficiencies in the Anaphylm human factors (HF) validation study.

These included instances of difficulty opening the pouch and incorrect film placement, which, if unaddressed, the FDA believes could cause significant safety issues in the setting of anaphylaxis.

What Next?

To resolve the FDA’s concerns, the company has modified the pouch opening, instructions for use, pouch and carton labeling, and plans to rapidly conduct a new HF validation study with these modifications.

The company also plans to further address potential tolerability issues in its resubmission.

Comparability data submitted as part of the Anaphylm NDA, such as bracketing, repeat dose, and sustainability, were not questioned in the CRL. There were also no CMC issues noted in the CRL.

Due to the requirements related to HF, clinical pharmacology requested a single pharmacokinetics (PK) study to understand the impact of any modifications to packaging and labeling. The FDA indicated that the HF and PK studies can be conducted in parallel. No additional studies were requested in the CRL.

Aquestive Therapeutics estimates resubmission in the early third quarter of 2026, assuming completion of the HF and PK studies and typical response times from the FDA. The company plans to request a rapid review by the FDA.

The company expects to submit its marketing authorization application in Europe as well as its New Drug Submission in Canada in the second half of 2026. The company also expects to receive feedback from the Medicines and Healthcare Products Regulatory Agency in the U.K. in the first quarter of 2026.

Analyst Take

Analyst Lachlan Hanbury-Brown expects Anaphylm’s approval decision in the first half of 2027.

AQST Price Action: Aquestive Therapeutics shares were up 45.25% at $4.28 at the time of publication on Monday, according to Benzinga Pro data.

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