ARS Pharma Announces Topline Results From Repeat Dosing Study Of neffy Under Nasal Allergen Challenge Conditions, Readies Data For Response To FDA's Complete Response Letter

Author: Benzinga Newsdesk | February 20, 2024 10:03am

Repeat doses of neffy under nasal allergen challenge demonstrate a pharmacokinetic profile greater than or similar to injection, and a pharmacodynamic profile greater than injection

 

Company believes completion of repeat dosing study and nitrosamine assessments address the deficiencies identified in the U.S. Food and Drug Administration (FDA)'s Complete Response Letter (CRL)

NDA on track to respond to CRL early in the second quarter of 2024 followed by an expected six-month review period

SAN DIEGO, Feb. 20, 2024 (GLOBE NEWSWIRE) -- ARS Pharmaceuticals, Inc. (NASDAQ:SPRY), a biopharmaceutical company dedicated to empowering at-risk patients and caregivers to better protect patients from severe allergic reactions that could lead to anaphylaxis, today announced topline results from its clinical study comparing repeat doses of neffy (epinephrine nasal spray) to repeat doses of epinephrine intramuscular (IM) injection, as requested by the FDA with and without nasal allergen challenge (NAC) conditions.

"We are very pleased with the topline results from our repeat dose study of neffy under nasal allergen challenge conditions, which we believe will address FDA's requests in their Complete Response Letter and support the approval of neffy for the treatment of Type I allergies, including anaphylaxis," said Richard Lowenthal, Co-Founder, President and CEO of ARS Pharma. "The study objective was to compare twice dosing with epinephrine injection and twice dosing with neffy under normal conditions and after nasal allergen challenge. The results show that the neffy pharmacokinetic and pharmacodynamic profile is greater than or similar to intramuscular injection, the comparator FDA requested for this study. In particular, repeat dosing in the same nostril was greater in exposure than dosing once in each nostril and greater than injection on both PK exposures and PD response at all time points, which may help inform labeling and instructions for use. With these results, we are completing the necessary work to submit our response to FDA in the next couple of months. We look forward to working with the Agency in our efforts to make neffy available to patients as soon as possible."

Based on the company's analysis of the data, we believe these results should support filing our response to the FDA's CRL. The repeat dose study under NAC conditions was designed with the FDA to address the Agency's outstanding questions regarding neffy as described in the Complete Response Letter (CRL) from September 2023. FDA did not provide guidance on a prespecified set of endpoints, but the data are anticipated to be informative to labeling if a second dose of neffy is needed.

ARS Pharma also completed the nitrosamine testing requested in the CRL per FDA's draft guidance issued in August 2023, with no measurable levels of nitrosamines detected.

Previously reported data with a single dose of neffy under NAC conditions showed accelerated absorption of neffy with exposures higher than IM injection during the early time period when clinical response to epinephrine is expected.

"When a severe, life-threatening allergic reaction occurs, it is necessary to administer epinephrine as soon as possible. Based on the single dose NAC data, my allergy colleagues and myself already believed that neffy would be effective under NAC conditions. FDA asked what would happen if NAC conditions occurred during the 10% of anaphylaxis events that require a repeat dose of epinephrine," says Thomas B. Casale, M.D., Professor of Medicine and Pediatrics and Chief of Translational Research in Allergy/Immunology at the University of South Florida in Tampa. "This study answers this question - exposures with repeat doses of neffy under NAC are at least as good as repeat doses of injection, and dosing in the same nostril is greater than injection. I believe the robust pharmacodynamic effect observed with repeat dosing in the same nostril or opposite nostrils compared to injection during nasal allergen challenge shows that neffy will be at least as effective as injection in reversing anaphylaxis symptoms, even during infrequently observed rhinitis of note. Together with the 100% response rate recently reported for neffy in treating pediatric oral food challenge-induced anaphylaxis, I believe this repeat dose NAC data provides further clinical evidence that neffy is effective under all relevant clinical conditions, and, if approved, supports its potential to provide an effective needle-free option for severe allergy patients and their families."

ARS Pharma intends to submit this repeat dose NAC study data to the FDA as part of its response to the CRL early in the second quarter of 2024.

"The safety and health of severe allergy patients is our shared priority. The neffy repeat dose NAC study should address the theoretical question FDA identified in the small subset of allergy patients who experience rhinitis and may require a second dose of epinephrine," says Sung Poblete, PhD, RN, CEO of FARE. "We are gratified that these data help to provide a complete picture of neffy use in the real world, and hopefully will resolve FDA's stated residual uncertainty. Now, nearly a year after the FDA Advisory Committee voted for its approval without any additional studies, we urge the FDA to move quickly to approve neffy and provide our community with a long-awaited, needle-free epinephrine treatment option. Allergy patients and their families are waiting."

neffy Repeat Dosing Study Design

The randomized, crossover pharmacokinetic (PK) and pharmacodynamic (PD) study enrolled 43 patients with seasonal allergic rhinitis who tested positive with a Total Nasal Symptom Score (TNSS) of ≥5 out of 12 and a congestion score of ≥2 out of 3 during the screening NAC. NAC involves spraying purified antigen directly onto the nasal mucosa – a ‘worst-case' experimental condition in contrast to real-world nasal conditions such as upper respiratory tract infections or acute allergic rhinitis from natural causes. All patients were dosed with epinephrine within 15 minutes of induction of the NAC during the peak effect, without allowing time for nasal symptoms to subside. A second dose of epinephrine was given to patients 10 minutes after the first dose per FDA labeling of epinephrine products.

FDA explicitly requested that ARS Pharma include intramuscular (IM) epinephrine given via manual syringe as the comparator in this study, as IM is the reference-listed drug and historical basis for efficacy of all other epinephrine products. Meta-analyses (Patel et al, JACI 2021) analyzing over 30,000 anaphylaxis events demonstrate that about 90% of events respond to a single dose of epinephrine injection irrespective of the delivery device, despite significant differences in PK.

Posted In: SPRY