First-in-Class Intranasal Epinephrine Spray for Anaphylaxis: Dose Finding Clinical Study

Lapidot, Tair et al. Journal of Allergy and Clinical Immunology: Global, Volume 0, Issue 0, 100487

Abstract

Background

Anaphylaxis is a life-threatening clinical presentation of acute systemic allergic reactions. Timely administration of epinephrine, usually by intramuscular autoinjector, is a robust life-saving treatment. Despite the critical necessity, there are multiple deterrants to patients’ proper use of epinephrine autoinjectors. FMXIN002 is a novel nasal dry powder formulation of epinephrine in a single-use device, offering first-in-class alternative treatment.

Objective

To measure epinephrine pharmacokinetics, pharmacodynamics and safety following a single administration of FMXIN002 at doses of 3.6 and 4.0 mg epinephrine versus IM autoinjector 0.3 mg, in healthy adults.

Methods

An open-label, single-dose, three-treatment, crossover, randomized, comparative bioavailability study with 12 healthy adults, female and male. FMXIN002 stability was also tested.

Results

FMXIN002 4.0 mg was absorbed faster and higher by most of the subjects, compared to IM autoinjector. 91% of subjects achieved the clinical threshold of 100 pg/mL plasma epinephrine at 6 minutes after administration of FMXIN002 4.0mg compared to 55% of subjects treated with IM autoinjector. AUC0-4min was significantly higher for FMXIN002 4.0 mg (geometric mean 7.49 hr*pg/mL vs. 2.06 hr*pg/mL, respectively, p=0.0377). The pharmacodynamic response and safety were comparable among all treatments. No serious adverse events occurred, all events were mild and self-resolved.

FMXIN002 was highly stable at all tested conditions including 5 years at 20ºC±5ºC.

Conclusions

FMXIN002 4.0 mg nasal spray enables faster and higher epinephrine plasma absorbance at the short therapeutic window required for the treatment of anaphylaxis, using a patient-friendly, needle-free, stable and safe device.

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