First-in-class intranasal epinephrine spray for anaphylaxis: Dose finding clinical study

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 deterrents to patients’ proper...

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Main Authors: Tair Lapidot, PhD, Yuval Tal, MD, PhD, Dalia Megiddo, MD, Galia Temtsin Krayz, PhD, Carolina Abrutzky, BSc, Simcha Blotnick, PhD, Oded Shamriz, MD, Alon Hershko, MD, PhD, Yoseph Caraco, MD
Format: Article
Language:English
Published: Elsevier 2025-08-01
Series:Journal of Allergy and Clinical Immunology: Global
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Online Access:http://www.sciencedirect.com/science/article/pii/S2772829325000888
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Summary: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 deterrents 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. Objectives: We sought to measure epinephrine pharmacokinetics, pharmacodynamics, and safety following a single administration of FMXIN002 at doses of 3.6 and 4.0 mg epinephrine versus intramuscular (IM) autoinjector 0.3 mg, in healthy adults. Methods: This was an open-label, single-dose, 3-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 in higher amounts 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 4.0 mg compared to 55% of subjects treated with IM autoinjector. The area under the curve for 0 to 4 minutes’ period was significantly higher for FMXIN002 4.0 mg (geometric mean: 7.49 h ∙ pg/mL vs 2.06 h ∙ pg/mL, respectively; P = .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 20 ± 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.
ISSN:2772-8293