FDA sets new PDUFA date for Anaphylm for type I allergic reactions

A needle-free, orally administered epinephrine option for type I allergic reactions moved closer to an FDA decision after the agency accepted the resubmitted New Drug Application (NDA) for dibutepinephrine (Anaphylm; Aquestive Therapeutics) sublingual film and assigned a Prescription Drug User Fee Act (PDUFA) goal date of March 16, 2027.¹

The FDA deemed the resubmission complete and classified it as a class 2 response, the company announced October 15, 2026.¹ Daniel Barber, president and CEO of Aquestive Therapeutics, said the acceptance "gives us a clear path forward for Anaphylm," adding that the company is preparing for a potential commercial launch in parallel with the review.¹

Anaphylm complete response letter and NDA resubmission timeline

Aquestive resubmitted the NDA on September 16, 2026, after the FDA issued a complete response letter (CRL) on January 30, 2026.¹ The original application sought approval for type I allergic reactions, including anaphylaxis, in patients weighing 30 kg or more.³ According to the company, the CRL centered on the human factors validation study, citing difficulty opening the pouch and incorrect film placement that the agency believed could pose significant safety risks during anaphylaxis, and requested a single supportive pharmacokinetic (PK) study. No chemistry, manufacturing, and controls issues were noted.³

Human factors and pharmacokinetic data for sublingual dibutepinephrine

The resubmission includes topline data from a new human factors study of revised packaging and instructions for use.² Among 105 participants, median time to open the pouch fell to 3 seconds, compared with 17 seconds in the earlier 166-participant study; the number of participants with difficulty opening the pouch dropped from 26 to 1, and incorrect placement dropped from 20 to 2.² No participants chewed or removed the film.²

In a PK study in healthy volunteers, geometric mean maximum plasma concentration (Cmax) was 391.7 pg/mL with self-administration, 357.6 pg/mL with clinician administration, and 334.5 pg/mL with manual intramuscular (IM) epinephrine. Median time to Cmax (Tmax) was 12 minutes for both film arms vs 45 minutes for IM injection.² An FDA-requested arm in which the film was deliberately misplaced produced lower exposure with top-of-tongue placement (Cmax >100 pg/mL; median Tmax, 35 minutes), although the company reported systolic blood pressure responses comparable with or greater than those of injectable epinephrine in a cross-study comparison.² No serious adverse events or discontinuations attributed to study drug occurred.²

Needle-free epinephrine and unmet need in pediatric anaphylaxis

When the FDA approved epinephrine nasal spray (neffy; ARS Pharmaceuticals) in August 2024 as the first epinephrine product for anaphylaxis not given by injection, the agency noted that some patients, particularly children, may delay or avoid treatment because of fear of injections.⁴ That approval was also limited to patients weighing at least 30 kg.⁴ If approved, Aquestive says Anaphylm would be the first oral rescue medication for severe allergic reactions.¹ The postage stamp–sized film begins dissolving on contact without water, and its packaging is designed to be carried in a phone case or wallet.¹

Jay Lieberman, MD, interim chief of allergy and immunology in the Department of Pediatrics at the University of Tennessee Health Science Center and a member of Aquestive's scientific advisory board, said, "Increasing options for patients is vital to improving outcomes in the real world."²

Dibutepinephrine prodrug and prior clinical development

Dibutepinephrine is an epinephrine prodrug formulated in a polymer matrix film.¹ The original NDA was supported by 11 clinical studies comprising approximately 967 administrations across 411 participants, including repeat-dose exposures and an allergen-induced oral allergy syndrome study, according to the company.³

References

1. Aquestive Therapeutics announces FDA acceptance of Anaphylm NDA resubmission and PDUFA goal date of March 16, 2027. News release. Aquestive Therapeutics. October 15, 2026. Accessed October 15, 2026. https://investors.aquestive.com/news-releases/news-release-details/aquestive-therapeutics-announces-fda-acceptance-anaphylmtm-nda

2. Aquestive Therapeutics announces positive topline human factors and pharmacokinetic study results for Anaphylm (dibutepinephrine) sublingual film. News release. Aquestive Therapeutics. August 10, 2026. Accessed October 15, 2026. https://investors.aquestive.com/news-releases/news-release-details/aquestive-therapeutics-announces-positive-topline-human-factors

3. Aquestive Therapeutics announces FDA issuance of complete response letter for Anaphylm. News release. Aquestive Therapeutics. February 2, 2026. Accessed October 15, 2026. https://investors.aquestive.com/news-releases/news-release-details/aquestive-therapeutics-announces-fda-issuance-complete-response

4. FDA approves first nasal spray for treatment of anaphylaxis. News release. US Food and Drug Administration. August 9, 2024. Accessed October 15, 2026. https://www.fda.gov/news-events/press-announcements/fda-approves-first-nasal-spray-treatment-anaphylaxis