Neffy Epi Data: Real-World Feedback and Congestion Studies

Nasal congestion from colds or seasonal allergies doesn’t interfere with the absorption of epinephrine from the nasal sprayer neffy, two studies find.

In addition to the new clinical trials, ARS Pharmaceuticals, the makers of the epinephrine nasal sprayer, is starting to collect real-world feedback from many allergists and pediatricians.

So far, 275 doctors who have used neffy to treat over 800 patients having allergic reactions in clinics have responded to a survey about how well it worked. The feedback is so far “very positive,” says Richard Lowenthal, ARS Pharmaceuticals’ president and CEO.

“The vast majority are saying the first dose is really good,” Lowenthal says. “Only about 6 percent have required a second dose.” (Previous research on epinephrine auto-injectors shows about 8 percent of reactions require a second dose.)

“This demonstrates neffy is working as well as injection,” Lowenthal says.

In 2024, the Food and Drug Administration approved neffy as the first needle-free treatment for severe allergic reactions due to food, insect sting or drug allergies. The 2 milligram (mg) sprayer is approved for adults and children weighing at least 66 pounds. On March 5, 2025, the FDA also approved 1 mg version for children 4 years and older, weighing 30 to 66 pounds.

Nasal Congestion Studies

The latest research on neffy, presented at the 2025 AAAAI/World Allergy Joint Congress, finds that nasal congestion doesn’t significantly impact absorption.

One study compared using the 2 mg sprayer against administering epinephrine with a syringe under various nasal conditions. The conditions included either nasal congestion due to colds or other viral infections, allergic rhinitis induced by having purified antigen (allergen) sprayed up the nose, or clear nasal passages. Some patients also received a second dose of neffy or epinephrine from a syringe.

Results showed some differences in peak blood concentrations of epinephrine. Those with viral infections had the highest epinephrine levels, followed by clear noses, and allergic rhinitis in third.

However, these differences were small and are unlikely to impact neffy’s effectiveness during anaphylaxis, says Dr. David Fleischer.

“It was really reassuring to show that neither of those conditions seem to affect the absorption of the drug and shouldn’t affect the efficacy,” says Fleischer, the study’s lead author. Fleischer is director of the Allergy and Immunology Center at Children’s Hospital Colorado.

Additionally, neffy under any nasal condition led to a higher peak epinephrine concentration than the .3 mg epinephrine syringe injection.

Blood concentration levels, along with changes in blood pressure and heart rate, indicate epinephrine absorption. In the U.S., these measures are used in testing of new epinephrine products as opposed to testing in patients experiencing severe allergic reactions.

2nd Study: Effect with Pollen Allergies

A second study included 20 Chinese adults with pollen-induced seasonal allergies. On three separate occasions, patients were exposed to their allergens in an allergen exposure chamber to provoke nasal congestion. On the first day, they used the neffy 2 mg sprayer. Then the subsequent times, they got syringe-injected epinephrine at the .3 mg and then the .5 mg dose.

Blood pressure and heart rate rose more with neffy. Blood levels of epinephrine peaked on average after about 14 minutes with neffy versus 30 minutes for epinephrine via syringe.

The peak blood concentration for neffy fell between the .3 mg and the .5 mg syringe concentrations. Side effects were mild and infrequent at less than 5 percent.

Reasons for Neffy Congestion Studies

The FDA had requested the nasal congestion studies before approval because of concerns that nasal congestion might lead to too much epinephrine absorption, Lowenthal explains. Allergic rhinitis increases the permeability of nasal membranes.

Another question was whether too little absorption could be caused by epinephrine draining out of a runny nose.

These results confirmed that nasal epinephrine remained within safe and effective levels across nasal conditions, Lowenthal says.

“No matter if you have nasal congestion from a cold or allergic rhinitis, you are still going to get to an effective level very, very quickly,” he says.

Clinical Trial Launching

The survey on real-world use, neffyExperience, will eventually include 2,500 allergists and pediatricians who have used neffy to treat allergic reactions in their practices.

“It’s amazing when physicians actually use it and see how fast it works. It changes how they see it and how they express it to patients,” Lowenthal says. “They go from saying, ‘It should work the same’ [as an auto-injector] to ‘I’ve used it and it works fantastic.’”

ARS Pharma is also launching a new trial in May 2025 to compare neffy to injected epinephrine in patients having an allergic reaction to a food challenge or immunotherapy shot. The trial will enroll 600 patients at 15 allergy clinics.

Patients will be randomized to receive either the nasal spray or epinephrine using a syringe. ARS Pharma had agreed with the FDA to do this study post-approval.

A 2024 study in Japan showed neffy reversed anaphylaxis in 15 children experiencing a serious reaction to a food allergen. The children in the study were undergoing oral food challenges at their doctor’s office when they had the reactions.

Insurance Coverage Expanding

Insurance coverage for neffy continues to expand. Neffy is now covered without prior authorization by Express Scripts, Cigna Healthcare, OptumRx, Navitus Health Systems, and Tricare. Prior authorization is needed for coverage other insurers. The nonprofit FAACT has published a chart with current neffy coverage here.

By this summer, Lowenthal expects that 80 percent of patients with commercial insurance will have access to neffy without prior authorization.

Neffy is also available without prior authorization for Medicaid recipients in Texas, Alabama and Montana. Additional states are expected to be added throughout 2025, Lowenthal says.

Updated March 26, 2025.