Aquestive Reports Improved Human Factors and Comparable PK for Anaphylm Ahead of NDA Resubmission

Aquestive Therapeutics reported topline human factors (HF) validation and pharmacokinetic (PK) results for Anaphylm, an investigational sublingual film containing the epinephrine prodrug dibutepinephrine. The data address deficiencies identified by the U.S. Food and Drug Administration (FDA) in a January 2026 Complete Response Letter (CRL) and support the company’s planned NDA resubmission in the third quarter of 2026.

Revised Packaging Improves Emergency Use

The new HF study evaluated revised pouch packaging, instructions for use, and pouch and carton labeling after the FDA identified problems with opening the pouch, tearing the film, incorrect placement in the mouth, chewing, and premature removal.

The revised packaging reduced the median pouch-opening time from 17 seconds to 3 seconds. Only 1 of 105 participants experienced difficulty opening the pouch, compared with 26 of 166 in the previous study.

Administration accuracy also improved substantially. The number of participants who incorrectly placed the film in the mouth fell from 20 of 166 to 2 of 105, an improvement of more than 80%. No participants chewed the film or prematurely removed it in the new HF study.

Self-Administration Produces Comparable PK

Study AQ109109 evaluated Anaphylm in healthy volunteers, comparing self-administration with clinician-administered Anaphylm and manual intramuscular (IM) epinephrine.

Self-administered Anaphylm produced a geometric mean maximum plasma concentration (Cmax) of 391.7 pg/mL, compared with 357.6 pg/mL following clinician administration. The median time to maximum concentration (Tmax) was 12 minutes for both Anaphylm administration methods.

By comparison, manual IM administration produced a geometric mean Cmax of 334.5 pg/mL and a median Tmax of 45 minutes. No administration errors occurred in the self-administration arm, supporting the feasibility of self-administration in the study setting.

Incorrect Placement Still Demonstrates Pharmacodynamic Activity

At the FDA’s request, a dedicated PK arm examined intentionally incorrect placement of Anaphylm on top of the tongue or the roof of the mouth.

While top-of-tongue administration resulted in lower overall exposure and a longer Tmax compared with correct sublingual administration, the geometric mean Cmax remained above 100 pg/mL, with a median Tmax of 35 minutes.

The company also reported clinically meaningful pharmacodynamic (PD) effects, measured by systolic blood pressure responses, that were comparable to or greater in magnitude than those observed with injectable epinephrine in a cross-study comparison.

Anaphylm Was Well Tolerated in the Reported Studies

No participant in the HF study or subject in the PK study prematurely removed the film. The PK study reported no serious adverse events and no treatment discontinuations due to adverse events.

Matthew Greenhawt, M.D., Aquestive’s chief medical officer, said the findings support the planned NDA resubmission, citing improvements in packaging usability and the PK results.

NDA Resubmission Planned for Q3 2026

Aquestive plans to include the HF validation and clinical PK data in its NDA resubmission and remains on track for submission in the third quarter of 2026, less than eight months after receiving the January CRL.

The company is also advancing regulatory submissions for Anaphylm in Canada, the UK, and the European Union.

If approved, Anaphylm could become a non-invasive, orally delivered epinephrine product for patients at risk of severe allergic reactions. The product remains investigational, and final approval of the Anaphylm proprietary name is contingent on FDA approval.

Reference

Aquestive Therapeutics Announces Positive Topline Human Factors and Pharmacokinetic Study Results for Anaphylm™ (dibutepinephrine) Sublingual Film | Aquestive Therapeutics