Anaphylm sublingual epinephrine film shows improved usability, comparable PK ahead of planned FDA resubmission

Aquestive Therapeutics has reported topline human factors (HF) and pharmacokinetic (PK) results for Anaphylm (dibutepinephrine) sublingual film, data the company says support a planned NDA resubmission to the FDA in the third quarter of 2026.¹ The studies address deficiencies cited in a Complete Response Letter (CRL) the agency issued January 30, 2026, which focused on packaging and administration technique rather than chemistry, manufacturing, or comparability data.²

"The topline results from our human factors and pharmacokinetic studies reinforce our confidence in the revised packaging design and instructions for use as we prepare for our planned NDA resubmission," said Daniel Barber, president and chief executive officer of Aquestive.¹ "If approved, we believe Anaphylm has the potential to be the first and only non-invasive, orally delivered epinephrine product for patients at risk of life-threatening allergic reactions."¹

Human factors and PK study design and findings

The new HF study tested a revised pouch, instructions for use, and labeling intended to correct problems identified in the original human factors study, in which some participants had difficulty opening the pouch, tore the film, misplaced it, chewed it, or removed it after administration.¹ In the revised study, median pouch-opening time fell from 17 seconds to 3 seconds, and the number of participants who had difficulty opening the pouch dropped from 26 of 166 to 1 of 105.¹ Incorrect film placement fell by more than 80%, from 20 of 166 participants to 2 of 105, and no participants chewed or removed the film.¹

A separate PK study in healthy volunteers compared self-administration with clinician-administered dosing and manual IM epinephrine injection. Self-administered Anaphylm produced a geometric mean Cmax of 391.7 pg/mL and median Tmax of 12 minutes, closely matching clinician-administered dosing (Cmax, 357.6 pg/mL; Tmax, 12 minutes) and outperforming manual IM injection on Tmax (45 minutes).¹ No administration errors, serious adverse events, or discontinuations occurred in the self-administration arm.¹

At the FDA's request, an additional PK arm evaluated deliberately misplaced dosing, with the film applied atop the tongue or roof of the mouth rather than sublingually.¹ Absorption was slower and lower under these conditions, as expected, but geometric mean Cmax remained above 100 pg/mL and produced pharmacodynamic changes in systolic blood pressure that the company characterized as comparable to or greater than those seen with injectable epinephrine in prior studies.¹

Clinical context: an underused standard of care

Epinephrine delivered by autoinjector remains first-line treatment for anaphylaxis, but carriage and correct use are inconsistent. Estimates place correct autoinjector technique as low as 16% to 32% in observational and self-report studies, and roughly half of patients do not consistently carry an unexpired device.³ Needle phobia and device complexity are frequently cited barriers, which has driven interest in non-injectable formulations such as sublingual films and nasal sprays.³

Drug background and regulatory history

Anaphylm is a polymer matrix-based epinephrine prodrug delivered as a small sublingual film that dissolves without water; it is one of more than 20 epinephrine prodrugs in Aquestive's AdrenaVerse platform.¹ The FDA's January 2026 CRL did not raise concerns about underlying comparability data but flagged human factors performance and requested an additional PK study, which the company has now completed.² Aquestive plans to request a rapid FDA review of the resubmission and is separately pursuing marketing applications in Canada, the United Kingdom, and the European Union.¹

Limitations and next steps

These are topline, sponsor-reported results that have not been peer reviewed or independently adjudicated by the FDA, and interim findings can shift once complete datasets are analyzed.¹ The misplaced-dosing PK arm used a cross-study comparison to prior autoinjector and manual IM data rather than a randomized head-to-head design, a limitation for interpreting the pharmacodynamic comparisons.¹ Whether the FDA agrees the revised packaging and instructions resolve the CRL's deficiencies will not be known until the agency completes its review of the resubmission.²

References

1. Aquestive Therapeutics, Inc. Aquestive Therapeutics announces positive topline human factors and pharmacokinetic study results for Anaphylm (dibutepinephrine) sublingual film. Published August 10, 2026. Accessed August 10, 2026. https://investors.aquestive.com/news-releases/news-release-details/aquestive-therapeutics-announces-positive-topline-human-factors

2. Aquestive Therapeutics, Inc. Aquestive Therapeutics announces FDA issuance of Complete Response Letter for Anaphylm. Published February 2, 2026. Accessed August 10, 2026. https://investors.aquestive.com/news-releases/news-release-details/aquestive-therapeutics-announces-fda-issuance-complete-response

3. Robinson LB, Camargo CA Jr, et al. Factors contributing to underuse of epinephrine autoinjectors in pediatric patients with food allergy. Ann Allergy Asthma Immunol. Published online 2020. Accessed August 10, 2026. https://pmc.ncbi.nlm.nih.gov/articles/PMC7498408/