Neffy FDA approval

Yes, you are correct. I have listed a recent clinical trial of nasal epinephrine pharmacodynamics and an economic analysis. Please clarify your question if you would like more information. I have not yet seen a patient who has used it during an allergic reaction.

References:
1. Greenhawt M, Lieberman J, Blaiss M, Bernstein DI, Oppenheimer J, DuBuske L, Fleischer D, Dworaczyk DA. Pharmacokinetic and Pharmacodynamic Profile of Epinephrine Nasal Spray Versus Intramuscular Epinephrine Autoinjector in Healthy Adults. J Allergy Clin Immunol Pract. 2024 Dec;12(12):3274-3282.e2. doi: 10.1016/j.jaip.2024.10.006. Epub 2024 Oct 10. PMID: 39395775.

Abstract
Background: Standard of care for anaphylaxis treatment is intramuscular (IM) epinephrine. An epinephrine nasal spray (ENS) is under development as an alternative form of administration.

Objective: To compare the pharmacokinetic and pharmacodynamic (PD) profile of 13.2 mg ENS with 0.3 mg IM epinephrine autoinjector.

Methods: Data from 4 open-label phase 1 crossover studies conducted in healthy adults were pooled to determine the pharmacokinetic and PD profile of a single 13.2 mg ENS dose delivered by 2 consecutive sprays of 6.6 mg each in opposite (n = 224 doses) or the same nostril (n = 75 doses) compared with the 0.3 mg IM autoinjector (n = 215 doses). Each participant served as their own control. Blood samples and vital signs were collected predose and at multiple intervals from 0 to 360 minutes postdose.

Results: ENS rapidly increased the plasma epinephrine concentration, with levels that were overall greater than IM autoinjector. Median (range) time to maximum plasma epinephrine concentration with ENS opposite nostrils, ENS same nostril, and IM autoinjector was 25.1 (1.3-362.1), 20.1 (3.0-120.2), and 20.0 (1.0-121.3) minutes, respectively. The area under the plasma concentration-time curve for 0 to 360 minutes was significantly higher with ENS than with the IM autoinjector (geometric mean ratio [90% CI], 155% [140%-172%] with ENS opposite nostrils, 159% [138%-182%] with ENS same nostril). The PD effects on heart rate and blood pressure were similar in pattern and magnitude among all 3 treatment groups.

Conclusions: ENS rapidly achieved plasma epinephrine levels greater and more sustained than the IM autoinjector and with a similar PD effect.

2. Shaker MS, Oppenheimer J, Rider NL, Golden DB, Anagnostou A, Greenhawt M. A Health Economic Analysis of Non-injectable Epinephrine Compared with Intramuscular Epinephrine. Ann Allergy Asthma Immunol. 2024 Dec 3:S1081-1206(24)01715-0. doi: 10.1016/j.anai.2024.11.025. Epub ahead of print. PMID: 39637974.

Background: Non-injectable epinephrine to treat allergic reactions addresses an unmet need. Intranasal epinephrine is approved and a sublingual form is under development. Inhaled epinephrine is poorly studied for anaphylaxis. These forms have unknown cost-effectiveness.

Objective: The aim of this research was to evaluate cost-effectiveness of commercially available non-injectable epinephrine compared with intramuscular epinephrine for treatment of anaphylaxis.

Methods: Markov cohort analyses evaluated the cost-effectiveness of non-injectable epinephrine forms. The base-case assumed exaggerated anaphylaxis fatality rates (50-fold increase) for using inhaled epinephrine given low certainty evidence in anaphylaxis, and deliberately reduced fatality risk for nasal or sublingual forms (10-fold reduction) theorizing higher adherence and early use during an allergic reaction.

Results: In the base-case scenario, assuming a 10-fold decreased risk in peanut allergy fatality associated with intranasal or sublingual epinephrine treatment for a severe allergic reaction (net monetary benefit [NMB] $2,189,134) vs. intramuscular (IM) epinephrine use (NMB, 2,189,114), intranasal or sublingual epinephrine was the most cost-effective option (incremental cost-effectiveness ratio [ICER] $83,748/QALY), but only at a marginal annual cost of $4. IM epinephrine was cost-effective (ICER, $17,900/QALY) vs. inhaled epinephrine (NMB, $2,183,531), although inhaled epinephrine reached cost-effectiveness (Willingness To Pay [WTP $100,000/QALY]) if associated fatality risk fell below 2.5-fold. Substituting a single non-injectable form of epinephrine for a second injectable device (in patients prescribed two autoinjectors already) would be cost-effective; however, adding a supplemental non-injectable device was not cost-effective, even assuming a 10-fold risk reduction with multiple device carriage (ICER $858,462).

Conclusion: Non-injectable routes of epinephrine can be cost-effective options provided fatality risk is not significantly elevated. Carriage of redundant epinephrine autoinjectors with non-injectable forms is not cost-effective if associated with excess cost of redundant device packs.

Carla M. Davis, MD, FAAAAI