ARS Pharmaceuticals, Inc. announced the publication of its full pharmacokinetic and pharmacodynamic results from one of its four primary registration studies of neffy (epinephrine nasal spray) in the Journal of Allergy and Clinical Immunology (JACI). JACI is the official scientific publication of the American Academy of Allergy, Asthma and Immunology and the most cited journal in the field of allergy and clinical immunology. The clinical study evaluated single and repeat doses of neffy compared to single and repeat doses of approved injection products in healthy subjects.

The study showed that neffy elicited comparable or greater response compared to approved injection products (intramuscular (IM) injection with needle and syringe, EpiPen), as measured by pharmacodynamic (PD) profile, the surrogate measure for assessing clinical effectiveness in anaphylaxis. These responses in PD were observed even at 1 minute after a single dose of neffy, with mean maximum changes in heart rate (Emax) statistically greater than both IM injection and EpiPen and mean maximum changes in blood pressure (Emax) statistically greater than IM injection and numerically greater than EpiPen. For repeat doses of neffy, mean maximum changes in PD responses for both blood pressure and heart rate were statistically greater than repeat doses of EpiPen.

Although the mean PD response for neffy was higher than EpiPen, the absolute maximum changes in blood pressure and heart rate for neffy (i.e., outliers) were comparable to EpiPen and within the range observed during normal activities such as exercise, ensuring neffy PD does not exceed the range observed with approved injection products for safety. The study also showed that neffy delivered consistent epinephrine levels to attain a pharmacokinetic (PK) profile in the range of approved injection products in healthy adult subjects. In addition, the PK profile for a second dose of neffy was approximately dose-proportional, unlike EpiPen, where the second dose delivered less incremental epinephrine exposure than the first dose.

There was also no difference in PK profile between twice dosing of neffy in the same versus different nostrils. neffy was well-tolerated, and all adverse events were mild. As reported previously, the most common adverse events in the neffy 2 mg registration program are mild nasal discomfort (9.7%) and mild headache (6.0%).

There is no meaningful pain or irritation as assessed by formal scales with mean VAS scores of 5 to 8 on a scale of 100. The article was also highlighted in the ?Latest Research? section of the American Academy of Allergy, Asthma and Immunology (AAAAI) website, which is the organization that develops treatment guidelines in the United States for severe allergies.

In May 2023, an FDA Advisory Committee (the Pulmonary-Allergy Drugs Advisory Committee (PADAC)) concluded a favorable benefit-risk profile of neffy for adults and children (=30 kg) for the treatment of patients with allergic reactions (Type I), including anaphylaxis. Although no member of the Committee requested a repeat dose study with neffy during allergen-induced allergic rhinitis, and ARS Pharma aligned with FDA in August 2023 that such a study could be completed as a post-marketing requirement, FDA is now requiring ARS Pharma to complete this study prior to approval as outlined in the Complete Response Letter for neffy sent on September 19, 2023. FDA stated in its PADAC briefing document that rates of any nasal mucosal symptoms, including rhinitis, range from 2% to 11% in anaphylaxis patients, with an average frequency reported in the literature of 5%.

After a single dose with neffy during allergen-induced allergic rhinitis, the FDA stated that 73% of patients with moderate to severe symptoms had complete resolution of nasal symptoms by 30 minutes after dosing, due to epinephrine?s well-known decongestant effects (Cleveland Clinic 2023, Epinephrine Nasal Spray). ARS Pharma plans to complete a repeat dose study with neffy in allergen-induced allergic rhinitis and file its NDA resubmission to the FDA in the first half of 2024, with an anticipated launch of neffy, if approved, in the second half of 2024. Type I severe allergic reactions are serious and potentially life-threatening events that can occur within minutes of exposure to an allergen and require immediate treatment with epinephrine, the only FDA-approved medication for these reactions.

While epinephrine autoinjectors have been shown to be highly effective, there are well-published limitations that result in many patients and caregivers delaying or not administering treatment in an emergency situation. These limitations include fear of the needle, lack of portability, needle-related safety concerns, lack of reliability, and complexity of the devices. There are approximately 40 million people in the United States who experience Type I severe allergic reactions due to food, venom, or insect stings.

Of those, only 3.3 million currently have an active epinephrine autoinjector prescription, and of those, only half consistently carry their prescribed autoinjector. Even if patients or caregivers carry an autoinjector, more than half either delay or do not administer the device when needed in an emergency.