New Jersey-based Aquestive Therapeutics, Inc. (Nasdaq: AQST) resubmitted its New Drug Application (NDA) to the US FDA for Anaphylm (dibutepinephrine) sublingual film, seeking approval for the treatment of Type I allergic reactions, including anaphylaxis. The resubmission follows an FDA Complete Response Letter (CRL) issued on January 30, 2026, which had identified deficiencies limited to packaging usability and a confirmatory pharmacokinetic (PK) study — leaving the original clinical efficacy and manufacturing data unchallenged.
The original NDA, submitted in March 2025, was supported by eleven independent clinical studies covering approximately 967 administrations across 411 subjects. The CRL did not question comparability data or raise any chemistry, manufacturing, and controls issues. Instead, the FDA cited a human factors validation study in which participants had difficulty opening the product pouch, incorrectly placed the film, and in some cases chewed or removed it — deficiencies the agency considered potentially dangerous in an emergency anaphylaxis setting.
In response, Aquestive redesigned the packaging and conducted two new studies. A human factors validation study using the revised packaging cut median pouch-opening time from 17 seconds to 3 seconds and reduced participants reporting difficulty opening the pouch from 26 of 166 to 1 of 105, with no observed film chewing or premature removal. A confirmatory PK study in healthy volunteers comparing self-administration, clinician administration, and manual intramuscular epinephrine reported no protocol-defined use errors in the self-administration arm, and showed self-administered Anaphylm achieved a geometric mean maximum plasma epinephrine concentration of 391.7 pg/mL versus 334.5 pg/mL for manual intramuscular epinephrine, with median time to maximum concentration of 12 minutes versus 45 minutes. Aquestive had previously aligned with the FDA on the study designs at a Type A meeting.
The FDA will determine the resubmission classification following its initial review, which will establish the applicable review timeline. A Class 1 designation carries a two-month review period; Class 2 carries six months.