neffy intranasal epinephrine spray provides alternative treatment choice for anaphylaxis
Published: August 19, 2023
Epinephrine auto-injectors (EAIs) are safe and effective for the treatment of severe allergic reactions, including anaphylaxis. However, patients and caregivers are often reluctant to carry and/or use them due to their large size, uncertainty about how to properly administer an injection, and fear of the needle. Delayed administration of epinephrine increases the risk of more serious outcomes, including hospitalization and death, thus there is currently a significant unmet need for alternative, needle-free epinephrine delivery options. neffy is an intranasal epinephrine nasal spray that is being developed to result in 1) plasma epinephrine levels that are within the range of currently approved injection products and 2) therapeutic increases in blood pressure and heart rate that are comparable to or better than the currently approved injection products.
The results of this Phase 1, six-treatment, two-part crossover study in 42 healthy adult subjects were published by Casale et al in The Journal of Allergy and Clinical Immunology (JACI). In Part 1, subjects were randomized to receive a single dose of neffy 2.0 mg, a single dose of EpiPen (0.3 mg epinephrine), and a single dose of epinephrine 0.3 mg delivered via manual intramuscular (IM) injection (Epinephrine IM 0.3 mg). In Part 2 subjects were randomized to receive two doses of neffy 2.0 mg, both in the right nare (neffy R/R), two doses of neffy 2.0 mg, one in the left nare and one in the right nare (neffy L/R), and two doses of EpiPen, one in the left thigh and one in the right thigh. Plasma epinephrine concentrations as well as changes in systolic blood pressure (SBP), diastolic blood pressure (DBP) and heart rate (HR) were assessed at regular post-dose intervals.
A single dose of neffy 2.0 mg resulted in a mean maximum plasma epinephrine level (Cmax) of 481 pg/mL, which was between Epinephrine IM 0.3 mg (339 pg/mL) and EpiPen (753 pg/mL). Two doses of neffy 2.0 mg resulted in a dose-proportional increases in mean Cmax (992 pg/mL following neffy R/R and 1000 pg/mL following neffy L/R). Repeated doses of EpiPen were not dose-proportional (840 pg/mL). Compared to the injection products, neffy elicited more robust and consistent therapeutic increases than injection products in both blood pressure and heart rate likely by avoiding the β2-mediated vasodilation resulting from injection directly into skeletal muscle, thereby minimizing the DBP drop and resulting suppression of SBP increase. There were no unexpected safety issues with neffy.
The results of this study demonstrate that neffy 2.0 mg is likely to be a safe and effective option for the treatment of severe allergic reactions, including anaphylaxis. neffy’s easy-to-use, needle-free design is expected to remove barriers to injectable epinephrine use, particularly for patients and caregivers who are anxious about administering IM injections. The expanded ability to quickly and safety administer epinephrine at the first sign of a severe allergic reaction will have a significant benefit for patients and their families.
The Journal of Allergy and Clinical Immunology (JACI) is an official scientific journal of the AAAAI, and is the most-cited journal in the field of allergy and clinical immunology.
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