Needle-Free Epinephrine Nasal Spray Shows Promise in Pediatric Food Allergy Anaphylaxis

Motohiro Ebisawa, MD, PhD

Photo courtesy of The Asia Pacific Academy of Pediatric
Allergy,Respirology & Immunology

Neffy, a needle-free epinephrine nasal spray, may be a safe and effective option for treating anaphylactic reactions caused by food allergies in children, according to new data published in The Journal of Allergy and Clinical Immunology: In Practice.¹

“The present study is the first prospective study conducted to assess both the efficacy of an epinephrine product during anaphylaxis, as well as to characterize the clinical course of anaphylaxis before and after administration of epinephrine,” investigators, led by Motohiro Ebisawa, MD, PhD, from the clinical research center for allergy and rheumatology at NHO Sagamihara National Hospital in Japan, and colleagues wrote.¹

Despite extensive safety and efficacy data, many people remain hesitant to use epinephrine, the only approved first-line treatment for severe allergic reactions, largely due to fear of injection. The US FDA approved neffy on August 9, 2024, eliminating patients’ top-cited fear^.2

Ebisawa and colleagues conducted a phase 3 clinical trial to evaluate the efficacy and safety of neffy for treating moderate allergic reactions during oral food challenges (OFCs) in pediatric patients with food allergies.¹

The open-label, single-dose study enrolled 15 Japanese children aged 6 to 17 years who experienced Grade 2 symptoms during OFCs. Participants received weight-based dosing of intranasal epinephrine: 1 mg for patients weighing 15–<30 kg and 2 mg for those ≥30 kg. Neffy was administered following the onset of moderate allergic symptoms involving gastrointestinal, respiratory, or cardiovascular systems.¹

All participants exhibited at least one Grade 2 clinical reaction. None required a second epinephrine dose for initial symptom resolution. One participant developed a biphasic reaction approximately 2 hours and 45 minutes after neffy administration and was treated with intramuscular epinephrine. The median time to resolution of Grade 2 symptoms was 16 minutes (range: 1–90 minutes).¹

Pharmacodynamic analyses showed increases in systolic blood pressure and heart rate consistent with epinephrine’s adrenergic activity. Adverse events related to neffy included tremor (20%) and nasal mucosal erythema (13.3%), all of which were mild or moderate. No patients experienced hemorrhage or nasal inflammation.¹

The authors noted that the availability of a needle-free epinephrine option could reduce administration hesitancy among patients and caregivers. However, they acknowledged the study’s small sample size and potential confounding factors, such as adjunctive treatments.¹

The findings support further evaluation of intranasal epinephrine as an alternative to intramuscular injection, particularly in scenarios where needle aversion may delay treatment.¹

“These data provide a bridge between neffy’s extensive PK and PD data which demonstrate activation of adrenergic receptors and the clinically measurable therapeutic effects of neffy,” Ebisawa and colleagues wrote. “In addition, the exploration of the PD response to epinephrine provides insights into the mechanism of action for the treatment of severe allergic reactions.”¹

References:

1. Ebisawa M, Takahashi K, Takahashi K, et al. Epinephrine nasal spray improves allergic symptoms in patients undergoing oral food challenge, phase 3 trial. J Allergy Clin Immunol Pract. Published online July 8, 2025. doi:10.1016/j.jaip.2025.06.038
2. Halsey G. FDA approves first intranasal epinephrine for emergency treatment of allergic reactions. Patient Care Online. August 9, 2024. https://www.patientcareonline.com/view/fda-approves-first-intranasal-epinephrine-for-emergency-treatment-of-allergic-reactions