Aquestive Therapeutics has received a complete response letter (CRL) from the US Food and Drug Administration (FDA) regarding its new drug application (NDA) for Anaphylm, a sublingual film formulation of dibutepinephrine.
The therapy aims to treat Type I allergic reactions, including anaphylaxis, in patients weighing 30kg or more.
The CRL highlights deficiencies in human factors validation for Anaphylm, such as incorrect film placement and difficulty opening the pouch, which the FDA indicated could cause safety risks during anaphylaxis.
Aquestive has modified the packaging and instructions for use and will conduct a new human factors validation study with these updates. The company will also address tolerability concerns in its resubmission.
No concerns were raised about comparability data or chemistry, manufacturing, and controls (CMC) in the CRL.
However, due to changes in human factors requirements, the FDA has requested a single pharmacokinetics (PK) study to assess any packaging or labelling modifications. The agency stated that human factors and PK studies may proceed concurrently.
Aquestive intends to request a Type A meeting with the FDA to review options for resubmission and expects to file its NDA again in the third quarter of 2026, following the completion of required studies.
The company continues regulatory activities for Anaphylm in Europe, the UK, and Canada. Positive feedback from European regulators means no additional clinical trials are currently required before submitting applications.
The original NDA included 11 clinical studies with nearly 967 total administrations across 411 participants.
Aquestive Therapeutics president and CEO Daniel Barber said: “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 labelling comments that will inform the final label for Anaphylm, if approved by the FDA.
“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. We look forward to working with the FDA to achieve approval for Anaphylm.”
In August 2025, Aquestive made a strategic funding agreement worth $75m with RTW Investments to support the potential launch of Anaphylm.
