Biopharmaceutical company ARS Pharmaceuticals has been given a Complete Response Letter (CRL) from the US Food and Drug Administration (FDA) for epinephrine nasal spray (neffy) treatment for Type 1 allergic reactions including anaphylaxis, in a move that may be surprising to those anticipating approval this week.¹

Once approved, neffy would have represented the first needle-free nasal spray epinephrine alternative for those with severe allergic reactions, potentially allowing for ease of use as well as administration.

Notably, the FDA’s new CRL was also shown to have requested a new pharmacokinetic/pharmacodynamic study in which repeat doses of neffy would be compared to an injection product under allergen-induced allergic rhinitis conditions.

This request for further study is also a unique development given the fact that the FDA’s Pulmonary-Allergy Drug Advisory Committee (PADAC) had voted favorably for neffy in May 2023 to approve the product without further efficacy or safety research.²

While the PADAC recommendations are known to be non-binding, the FDA typically includes the committee’s vote in its overall assessment and review of pending New Drug Applications. The President, co-founder, and CEO of ARS Pharma, Richard Lowenthal, responded to the FDA decision.

“We are very surprised by this action and the late requirement at this time to change the repeat-dose study from a post-marketing requirement, which we had previously aligned on with FDA, to a pre-approval requirement, particularly given the positive Advisory Committee vote,” Lowenthal said in a statement. “In fact, multiple Committee members highlighted the favorable profile of neffy in our completed single-dose nasal allergy challenge study and that any decline in exposure 20 minutes after dosing, after the expected response period, is of no concern.”

The PADAC’s May 2023 meeting had led to significant support for neffy, with strong benefit-risk profiles observed for both adults and children ≥30 kg. Notably, there were no concerns raised with the committee regarding the finished single-dose nasal allergy challenge study.

The company reportedly plans to appeal the new decision through the use of a Formal Dispute Resolution Request (FDRR). Additionally, the company plans to resubmit neffy to the FDA by the first half of 2024, seeking an action date by the organization in the second half of the same year.

The FDA’s CRL also requested testing for nitrosamine impurities that were based upon new draft guidance issued post-neffy NDA submission, and those at ARS Pharma believe this will not substantially delay the product’s resubmission.

Type 1 reactions in patients with allergies are recognized as serious and even potentially life-threatening, necessitating prompt treatment following exposure. Epinephrine currently stands as the only FDA-approved medication designed for management of these reactions.

An estimated 25 to 40 million individuals in the US fall into the Type 1 allergic reaction category, according to ARS Pharma officials, and the company has noted that only 3.3 million of them are known to have prescriptions for active epinephrine autoinjectors.

“We stand by the totality of the neffy data package generated in a comprehensive registration program that was aligned upon with FDA and believe strongly in the value neffy can provide for patients, families and caregivers living daily with severe allergic reactions,” Lowenthal noted in his statement.

References

1. ^{FDA Issues Complete Response Letter for neffy® (epinephrine nasal spray) New Drug Application with Request for Additional Study. GlobeNewswire. September 20, 2023. https://www.globenewswire.com/news-release/2023/09/20/2746095/0/en/FDA-Issues-Complete-Response-Letter-for-neffy-epinephrine-nasal-spray-New-Drug-Application-with-Request-for-Additional-Study.html. Date accessed: September 20, 2023.}
2. ^{ARS Pharmaceuticals. FDA Advisory Committee Votes in Support of Favorable Benefit-Risk Profile for neffy® (Intranasal (IN) Epinephrine) for the Treatment of Allergic Reactions (Type 1), Including Anaphylaxis [press release]. Published May 11, 2023. Accessed May 11, 2023. https://ir.ars-pharma.com/news-releases/news-release-details/fda-advisory-committee-votes-support-favorable-benefit-risk}
3. ^{Grossi G. David Dworaczyk, PhD: FDA Review is Anticipated for an Epinephrine Nasal Spray. HCPLive. May 9, 2023. https://www.hcplive.com/view/david-dworaczyk-phd-fda-review-is-anticipated-for-an-epinephrine-nasal-spray.}