Aquestive Therapeutics received an FDA Complete Response Letter for Anaphylm, its investigational sublingual epinephrine film for anaphylaxis, citing human factors issues and requesting a supportive PK study ahead of a planned Q3 2026 resubmission.
Written By: Pharmacally Medical News Desk
Aquestive Therapeutics, Inc. has received a Complete Response Letter (CRL) from the U.S. Food and Drug Administration (FDA) regarding its New Drug Application (NDA) for Anaphylm™ (dibutepinephrine) Sublingual Film, an investigational non-invasive epinephrine therapy intended for the treatment of Type I allergic reactions, including anaphylaxis, in patients weighing 30 kg or more.
The CRL was issued on January 30, 2026, and the company stated that the FDA’s concerns were limited primarily to human factors validation and supportive pharmacokinetics requirements, with no manufacturing or chemistry-related issues raised.
FDA Focuses on Human Factors and Labeling Concerns
According to the company, the FDA’s response centered on deficiencies identified in Anaphylm’s human factors (HF) validation study. Reported issues included difficulty opening the product pouch and incorrect placement of the sublingual film. The agency highlighted that these usability challenges could pose significant safety risks in emergency situations such as anaphylaxis.
To address these findings, Aquestive has already implemented modifications to the packaging and instructions, including improved pouch-opening design, updated instructions for use and revised pouch and carton labeling.
The company plans to conduct a new HF validation study incorporating these updates and will also further evaluate potential tolerability considerations in its resubmission.
The FDA did not raise concerns regarding comparability data submitted in the NDA, including repeat-dose and sustainability assessments, and no chemistry, manufacturing, and controls (CMC) deficiencies were identified.
Supportive PK Study Requested Alongside HF Updates
In addition to usability corrections, the FDA requested a single clinical pharmacokinetics (PK) study to understand the impact of packaging and labeling changes on drug performance.
The agency confirmed that the HF and PK studies may be conducted in parallel, and no additional clinical trials were required beyond these measures.
Company Plans Type A Meeting and Q3 2026 Resubmission
Daniel Barber, President and CEO of Aquestive, expressed confidence in the program despite the setback, noting that the issues were specific and addressable.
The company plans to request a Type A meeting with the FDA as an initial step toward a rapid resubmission strategy. Based on its current assessment, Aquestive anticipates resubmitting the NDA in the third quarter of 2026, assuming timely completion of the required studies and standard FDA response timelines.
Jay Lieberman, M.D., Professor at the University of Tennessee Health Science Center, emphasized that the FDA’s feedback was focused on patient experience and device usability rather than drug efficacy.
He highlighted the continued underuse of epinephrine in anaphylaxis and suggested that additional easy-to-use treatment options remain an important need for patients and clinicians.
Global Regulatory Expansion Continues
Beyond the U.S., Aquestive continues to advance Anaphylm’s global development strategy, with regulatory engagement already underway in Canada, Europe and United Kingdom.
The company reported receiving positive feedback from the European Medicines Agency (EMA), indicating that no further clinical trials would be needed before submission. Regulatory filings in Europe and Canada are expected in the second half of 2026, while feedback from the UK MHRA is anticipated in early 2026.
Clinical Program and Product Profile
Anaphylm is a polymer-based epinephrine prodrug sublingual film designed as a potential alternative to injectable auto-injectors. The NDA submission was supported by an extensive clinical development program consisting of 11 independent clinical studies, approximately 967 total administrations, 411 subjects enrolled, comparable PK profile to leading epinephrine auto-injectors. The therapy was generally well tolerated, with a safety profile consistent with epinephrine.
Anaphylm is designed to dissolve rapidly under the tongue without water or swallowing and is packaged in a compact, weather-resistant pouch suitable for pocket carry.
Funding and Next Steps
Aquestive stated it has sufficient financial resources to complete the U.S. approval process and prepare for launch, while also progressing applications internationally.
The company will host a conference call on February 2, 2026, to provide additional regulatory and program updates.
This CRL follows earlier FDA scrutiny raised earlier this month regarding Anaphylm’s regulatory review. You can read our previous report here Click Here
References
Aquestive Therapeutics Announces FDA Issuance of Complete Response Letter for Anaphylm™, 02 Feb 2026, https://investors.aquestive.com/news-releases/news-release-details/aquestive-therapeutics-announces-fda-issuance-complete-response
Aquestive Therapeutics Reports FDA-Identified Deficiencies in Anaphylm NDA, Review Continues, 13 January 2026, https://pharmacally.com/aquestive-therapeutics-reports-fda-identified-deficiencies-in-anaphylm-nda-review-continues/