In a surprising twist, the FDA dealt a setback to ARS Pharmaceuticals on Tuesday by rejecting its application for the groundbreaking epinephrine nasal spray known as Neffy. This innovative nasal spray was poised to become the first needle-free treatment for severe allergic reactions in the United States, targeting both adults and children weighing at least 30 kg.
The FDA’s decision, outlined in a Complete Response Letter (CRL), demands an additional study examining the pharmacokinetics and pharmacodynamics of repeated Neffy doses compared to repeated administrations of traditional epinephrine injections in individuals with allergen-induced allergic rhinitis.
What makes this rejection even more perplexing is that the FDA’s request appears to contradict their previous stance. Just last August, the FDA and ARS were in alignment regarding the need for this study, albeit as a post-marketing requirement. They had even finalized the physician’s labeling for the product.
Adding to the intrigue, the FDA’s Pulmonary-Allergy Drugs Advisory Committee (PADAC) had voted overwhelmingly in favor of Neffy’s risk-benefit profile in May 2023. The panel of external experts voted 16-6 in favor of Neffy’s use in adults and 17-5 in favor of its use in children aged 18 years and younger.
While the FDA isn’t bound by the recommendations of its advisory committees, ARS CEO Richard Lowenthal expressed deep surprise at the regulator’s decision, especially the last-minute shift from a post-marketing requirement to a pre-approval necessity.
Undeterred, ARS plans to file a Formal Dispute Resolution Request to appeal the FDA’s CRL. Moreover, because the company had previously committed to conducting a post-marketing repeat-dose study, they anticipate resubmitting Neffy’s drug application in the first half of 2024, with an expected FDA verdict in the latter half of the same year.
Alongside the repeat-dose study, the CRL issued on Tuesday also calls for additional data on nitrosamine impurities, aligning with draft testing guidelines. ARS, however, doesn’t foresee this new requirement as a major obstacle to their resubmission efforts.
ARS had presented a compelling case for Neffy’s regulatory approval, backed by data from four primary registrational studies. These studies demonstrated that a 2-mg Neffy dose had a pharmacokinetic profile well within the range of approved injectable epinephrine formulations.
The journey to approval for Neffy had already faced some delays. The FDA had accepted the New Drug Application in October 2022 but extended the review period by three months in June 2023. Surprisingly, at that point, the agency had not requested additional pre-marketing studies.
During the May 2023 PADAC meeting, FDA reviewers had raised concerns about the lack of clinical data supporting Neffy’s efficacy and safety. They pointed out the scarcity of pharmacokinetic and pharmacodynamic data for injected epinephrine products, creating uncertainties in comparisons. The distinct routes of administration further complicated the assessment.
If ultimately approved, Neffy would revolutionize the landscape as the first needle-free epinephrine treatment for severe allergic reactions in the U.S. ARS remains steadfast in their belief in the value Neffy can bring to patients, families, and caregivers grappling with the challenges of severe allergic reactions.