Anaphylm Resubmission Data Clears Usability Bar But Leaves Clinical Outcome and Pediatric Gaps Open

Aquestive's Anaphylm Studies Bolster NDA Resubmission for Anaphylaxis

Aquestive Therapeutics announced positive topline results from its human factors (HF) validation and pharmacokinetic (PK) studies for Anaphylm™ (dibutepinephrine) sublingual film. These results support the planned resubmission of its New Drug Application (NDA) to the U.S. FDA for treating Type 1 allergic reactions, including anaphylaxis. The revised packaging design significantly reduced the median pouch opening time from 17 to 3 seconds, and incorrect film placement decreased by over 80%. PK data showed self-administered Anaphylm achieved a geometric mean Cmax of 391.7 pg/mL and median Tmax of 12 minutes, comparable to clinician-administered results and faster than manual IM administration (Cmax 334.5 pg/mL, Tmax 45 minutes). Even with incorrect top-of-tongue placement, clinically meaningful pharmacodynamic results were observed. The company plans NDA resubmission in Q3 2026.

• The human factors study demonstrated significant improvements in Anaphylm's usability, addressing previous FDA concerns. The revised packaging design reduced the median time to open the pouch from 17 seconds to just 3 seconds. Additionally, updated instructions for use led to an over 80% reduction in incorrect film placement, enhancing patient safety and ensuring proper administration during critical allergic reactions, which is crucial for an emergency medication.
• The pharmacokinetic study in healthy volunteers revealed a favorable profile for Anaphylm. Self-administered Anaphylm achieved a geometric mean Cmax of 391.7 pg/mL and a median Tmax of 12 minutes. These results were comparable to clinician-administered Anaphylm (Cmax 357.6 pg/mL, Tmax 12 minutes) and significantly faster than manual intramuscular epinephrine administration (Cmax 334.5 pg/mL, Tmax 45 minutes), indicating rapid drug absorption and a quick onset of action.
• A crucial finding highlighted Anaphylm's robustness to administration errors. Even when placed incorrectly on top of the tongue, the film still delivered clinically meaningful pharmacodynamic results. This 'misplaced administration' arm showed a geometric mean Cmax above 100 pg/mL and a median Tmax of 35 minutes, with PD results comparable to or greater in magnitude than injectable epinephrine, providing an important safety margin for real-world use by patients and caregivers.
• These positive study results are pivotal for Aquestive Therapeutics' planned resubmission of the Anaphylm New Drug Application (NDA) to the U.S. FDA in the third quarter of 2026. The data directly addresses deficiencies noted in a previous Complete Response Letter, reinforcing the company's confidence in Anaphylm's potential as the first non-invasive, orally delivered epinephrine product for severe allergic reactions, including anaphylaxis.

Addressing the Critical Gaps in Anaphylaxis Management

Current treatment approaches for Type 1 allergic reactions and anaphylaxis are hampered by a convergence of clinical, psychological, and economic barriers. Despite the availability of established first-line therapies, real-world management frequently falls short of guideline recommendations, leaving patients at continued risk.

• Adrenaline auto-injector (AAI) underutilization: Epinephrine remains the cornerstone of anaphylaxis management, yet its administration is consistently suboptimal in practice. Parents and caregivers demonstrate marked reluctance to use AAIs, driven primarily by fear of the injection itself — a hesitancy that persists even among individuals who have received formal device training and are deemed knowledgeable regarding indications for use.

• Psychological barriers beyond technical training: Eliminating hesitancy around AAI use requires more than device instruction. Fear and anxiety surrounding self- or proxy-administration represent independent obstacles, indicating that effective anaphylaxis preparedness must incorporate psychological support interventions alongside technical coaching to build adequate confidence.

• Allergen immunotherapy safety profile: Subcutaneous immunotherapy carries a measurable risk of systemic reactions, reported at approximately 1 per 1,000 injection visits (0.1%), with life-threatening anaphylactic events estimated at 1 per 160,000 injection visits and documented cases of near-fatal and fatal anaphylaxis. Sublingual immunotherapy presents a high incidence of local application-site reactions, though severe anaphylactic events remain uncommon by comparison.

• Oral immunotherapy limitations: While oral immunotherapy has demonstrated promising efficacy, its broader adoption is constrained by ongoing safety concerns, adherence challenges, and uncertainty regarding the durability of induced tolerance.

• Biologic therapy access and evidence gaps: Biologics targeting type 2 inflammation face barriers related to accessibility, prohibitive cost — particularly for omalizumab — and insufficient long-term safety data, limiting their integration into routine clinical management.

• Conventional pharmacotherapy shortcomings: Antihistamines and corticosteroids are associated with clinically relevant side effects and are frequently perceived by patients as insufficiently effective, further complicating the long-term management of allergic disease.

Anaphylm's Human Factors and PK Data Pave Way for Resubmission

A Phase 3 open-label study evaluating neffy (epinephrine nasal spray) enrolled 15 food allergy patients aged 6 to 17 years undergoing oral food challenge (OFC). Dosing was weight-based: patients weighing 15–<30 kg received neffy 1 mg, while those ≥30 kg received neffy 2 mg. All 15 patients exhibited at least one Grade 2 anaphylaxis symptom following the OFC. The median time to symptom resolution was 16 minutes, and no patients required a second dose of epinephrine for the initial reaction. One patient developed a biphasic reaction 2 hours and 45 minutes post-administration, which was managed with intramuscular epinephrine. No serious adverse events were reported; adverse events not attributable to the OFC included tremor in 3 patients (20.0%) and nasal mucosal erythema in 2 patients (13.3%).

Across the broader neffy development program, multiple clinical trials evaluated pharmacokinetic (PK) and pharmacodynamic (PD) responses under varied conditions — including self-administration scenarios, allergic and infectious rhinitis states, and an animal anaphylaxis model of severe hypotension. neffy is formulated from three FDA-approved components: epinephrine, Intravail A3 (an absorption enhancer), and a Unit Dose Spray (UDS) device. These studies demonstrated a PK profile within the range of approved injectable epinephrine products, with PD responses comparable to or exceeding those of injection formulations. Notably, increases in pulse rate and blood pressure were observed as early as one minute post-administration, confirming activation of both α- and β-adrenergic receptors — the pharmacological basis of epinephrine's therapeutic effect in anaphylaxis. Collectively, these data support neffy as a safe and effective needle-free alternative for the treatment of severe allergic reactions, including anaphylaxis.

Anaphylm's PK/PD Profile: Benchmarking Against Current Epinephrine Options

Investigational therapies for Type 1 allergic reactions and anaphylaxis span multiple mechanistic classes, each benchmarked against intramuscular (IM) epinephrine as the established standard of care. Emerging data highlight both pharmacokinetic advantages of novel epinephrine delivery formats and longer-term disease-modifying potential from immunologic approaches. The table below summarizes the key comparisons across modalities reported in published literature.