FDA Issues Complete Response Letter for Aquestive's Anaphylm Sublingual Film

Aquestive Therapeutics, Inc. (NASDAQ: AQST) received a Complete Response Letter (CRL) from the U.S. Food and Drug Administration on January 30, 2026 for the New Drug Application seeking approval of Anaphylm (dibutepinephrine) Sublingual Film for the treatment of Type I allergic reactions, including anaphylaxis, in patients weighing 30kg or more (approximately 66 pounds). The deficiencies are limited to packaging and administration.

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. 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.

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 Agency indicated that the HF and PK studies can be conducted in parallel. No additional studies were requested in the CRL. 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.

The Company believes it can rapidly resolve deficiencies and expects to resubmit as early as Q3 2026. The Company plans to request a Type A meeting with the FDA to discuss the most efficient path forward for resubmission. Based on its initial review of the CRL, the Company estimates resubmission in Q3 2026, assuming completion of the HF and PK studies and typical response times from the FDA. The Company plans to request rapid review by the FDA.

Prior to the CRL, the FDA notified Aquestive on January 9, 2026 that it had identified deficiencies in the NDA that preclude discussion of labeling and post-marketing commitments at this time. The FDA stated that the notification does not reflect a final decision on the pending application and the FDA's review remains ongoing. The FDA indicated that the review remains ongoing and further clarified that a Discipline Review Letter will not be issued, while information requests are possible during the remaining review period. The scheduled PDUFA action date was January 31, 2026.

The Anaphylm NDA submission is supported by a comprehensive clinical development program consisting of eleven independent clinical studies with approximately 967 total administrations across 411 subjects, including 840 single-dose and 127 repeat-dose exposures of Anaphylm. As part of the clinical development program, Aquestive conducted a first-of-its-kind oral allergy syndrome (OAS) study, which demonstrated Anaphylm's performance in a real-world, allergen-induced setting. The program demonstrated that Anaphylm delivers a pharmacokinetic (PK) profile comparable to the leading epinephrine auto-injectors. These studies showed that Anaphylm was generally well tolerated and had a safety profile similar to that of epinephrine.

Aquestive continues to advance its global expansion strategy for Anaphylm, having initiated regulatory engagements in Canada, Europe, and the United Kingdom in 2025. The Company received positive feedback from the European Medicines Agency (EMA) that no further clinical trials are needed prior to regulatory approval submission. Aquestive expects to submit its marketing authorization application in Europe as well as its New Drug Submission (NDS) in Canada in the second half of 2026. The Company also expects to receive feedback from the Medicines and Healthcare Products Regulatory Agency (MHRA) in the United Kingdom in the first quarter of 2026.

The Company remains well-capitalized and anticipates ending 2026 with significant cash. Unaudited cash and cash equivalents were approximately $120 million as of December 31, 2025. As previously planned, the Company intends to hire its U.S. sales force following approval, if granted by the FDA, and continues to advance other pre-commercial activities for Anaphylm.

A securities fraud class action lawsuit was filed in the United States District Court for the District of New Jersey on behalf of investors who purchased or acquired the securities of Aquestive between June 16, 2025 and January 8, 2026, inclusive, alleging violations of the Securities Exchange Act of 1934 against the Company and certain of its senior officers. According to the lawsuit, Defendants made misrepresentations concerning Aquestive's New Drug Application for Anaphylm (Dibutepinephrine) sublingual film. The lead plaintiff filing deadline is May 4, 2026.