Epinephrine nasal spray potential and additional option for treating type 1 anaphylaxis
Epinephrine is used for treating severe allergic reactions, including anaphylaxis. Several epinephrine injection products are approved, but differences in their pharmacokinetic (PK) and pharmacodynamic (PD) profiles have been reported. Despite this, all approved products are considered efficacious. Epinephrine auto-injectors (EAIs) are safe and effective but inconvenient and cumbersome in a recent study published in The Journal of Allergy and Clinical Immunology. Thomas B. Casale and colleagues have said that neffy's needle-free IN administration is anticipated to offer a safe and effective means of delivering epinephrine, which would benefit patients who are hesitant and delay to take the dosing due to needle phobia.
Neffy 2.0 mg was formulated to have a PK profile within the range of currently approved epinephrine injection products. EpiPen has the fastest and highest Cmax, and manual IM injection has the slowest and lowest Cmax. Both these comparators were included in this study. The study results showed that the PD profile of neffy is comparable to EpiPen and comparable to or better than Epinephrine IM injection, indicating that neffy may be at least as efficacious as these approved products.
Epinephrine is the first-line treatment for managing severe allergic reactions, which is associated with lower hospitalization and death rates. However, current treatment options, such as epinephrine auto-injectors and manual intramuscular injections, are often considered inconvenient and challenging to use, even during severe reactions. To address this issue, an intranasal epinephrine delivery device called neffy has been developed as an alternative option.
This study assessed the comparative PK and PD of neffy 2.0 mg, EpiPen 0.3 mg, and manual intramuscular injection 0.3 mg. This study was a phase 1, randomized, 6-treatment, 6-period, 2-part crossover study conducted in 59 healthy subjects. PK and PD parameters were assessed before dosing and at various postdose intervals.
The mean maximum plasma concentrations with single doses of epinephrine for manual injection, neffy and EpiPen were 339 pg/ml, 481 pg/ml and 753 pg/ml, respectively. When dosed both once and twice, neffy had a more pronounced increase in pharmacodynamic parameters relative to EpiPen or manual injection.
They said that neffy's pharmacokinetic profile was bracketed by approved injection products, with PD responses comparable to or better than approved injection products.
They mentioned, "neffy is expected to be both a safe and effective option for those who are reluctant to carry and use injection devices."
This study was conducted in healthy volunteers, and this was the major limitation of this study. It is essential to evaluate epinephrine efficacy based on the available data with healthy volunteers and subjects with local allergic reactions, as well as with preclinical data and vast clinical experience.
Reference:
Casale, Thomas B., et al. “Pharmacokinetics/Pharmacodynamics of Epinephrine After Single and Repeat Administration of Neffy, EpiPen, and Manual Intramuscular Injection.” Journal of Allergy and Clinical Immunology, Elsevier BV, Aug. 2023. Crossref, https://doi.org/10.1016/j.jaci.2023.08.007.
