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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Elsevier
2025-08-01
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| 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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| author | 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 |
| author_facet | 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 |
| author_sort | Tair Lapidot, PhD |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-d529867dfa8042309bb0d8f5780ab79f |
| institution | DOAJ |
| issn | 2772-8293 |
| language | English |
| publishDate | 2025-08-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Journal of Allergy and Clinical Immunology: Global |
| spelling | doaj-art-d529867dfa8042309bb0d8f5780ab79f2025-08-20T03:00:25ZengElsevierJournal of Allergy and Clinical Immunology: Global2772-82932025-08-014310048710.1016/j.jacig.2025.100487First-in-class intranasal epinephrine spray for anaphylaxis: Dose finding clinical studyTair Lapidot, PhD0Yuval Tal, MD, PhD1Dalia Megiddo, MD2Galia Temtsin Krayz, PhD3Carolina Abrutzky, BSc4Simcha Blotnick, PhD5Oded Shamriz, MD6Alon Hershko, MD, PhD7Yoseph Caraco, MD8Nasus Pharma Ltd, Tel Aviv, Israel; Corresponding author: Tair Lapidot, PhD, Nasus Pharma Ltd, 65 Yigal Alon St, Tel Aviv, 6744316, Israel.Allergy and Clinical Immunology Unit, Hadassah Medical Center, Faculty of Medicine, Hebrew University of Jerusalem, Jerusalem, IsraelNasus Pharma Ltd, Tel Aviv, IsraelFormulex Pharma Innovation Ltd, Nes Ziona, IsraelNasus Pharma Ltd, Tel Aviv, IsraelClinical Pharmacology Unit, Hadassah Medical Center, Faculty of Medicine, Hebrew University of Jerusalem, Jerusalem, IsraelAllergy and Clinical Immunology Unit, Hadassah Medical Center, Faculty of Medicine, Hebrew University of Jerusalem, Jerusalem, IsraelDepartment of Internal Medicine, Hadassah Medical Center, Faculty of Medicine, Hebrew University of Jerusalem, Jerusalem, IsraelClinical Pharmacology Unit, Hadassah Medical Center, Faculty of Medicine, Hebrew University of Jerusalem, Jerusalem, IsraelBackground: 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.http://www.sciencedirect.com/science/article/pii/S2772829325000888Anaphylaxisallergyintranasalbioavailabilityepinephrinepowder |
| spellingShingle | 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 First-in-class intranasal epinephrine spray for anaphylaxis: Dose finding clinical study Journal of Allergy and Clinical Immunology: Global Anaphylaxis allergy intranasal bioavailability epinephrine powder |
| title | First-in-class intranasal epinephrine spray for anaphylaxis: Dose finding clinical study |
| title_full | First-in-class intranasal epinephrine spray for anaphylaxis: Dose finding clinical study |
| title_fullStr | First-in-class intranasal epinephrine spray for anaphylaxis: Dose finding clinical study |
| title_full_unstemmed | First-in-class intranasal epinephrine spray for anaphylaxis: Dose finding clinical study |
| title_short | First-in-class intranasal epinephrine spray for anaphylaxis: Dose finding clinical study |
| title_sort | first in class intranasal epinephrine spray for anaphylaxis dose finding clinical study |
| topic | Anaphylaxis allergy intranasal bioavailability epinephrine powder |
| url | http://www.sciencedirect.com/science/article/pii/S2772829325000888 |
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