The Food and Drug Administration’s (FDA) Pulmonary-Allergy Drug Advisory Committee voted 16:6 in favor for adults, and 17:5 in favor for children (<18 years of age and ≥30kg), that available data support a favorable benefit-risk assessment for neffy® in the treatment of severe allergic reaction (Type 1), including anaphylaxis, for adults and children who weigh more than 30kg.
Neffy is an intranasal formulation of epinephrine. The application was supported by pharmacokinetic (PK)/pharmacodynamic (PD) data comparing the nasal spray formulation to epinephrine injection. Findings showed comparable epinephrine levels in the blood between the nasal and intramuscular formulations, including within the first 10 to 20 minutes after administration.
However, the panel noted that without a clinical efficacy trial, there were uncertainties with relying on PK/PD data given the severity of the indication. They specifically pointed to findings from a nasal allergen challenge study, which was designed to mimic nasal mucosa changes during anaphylaxis (eg, severe congestion, edema). Results showed a rapid increase in epinephrine PK with nasal administration compared with IM administration, followed by a rapid decline in epinephrine concentration 10 to 20 minutes postdose.
In the briefing document, the panel wrote that “the lack of epinephrine PK/PD sustainability under nasal allergen challenge conditions raises concerns for durability of effect, and the need for a repeat dose, in patients with anaphylaxis who experience nasal edema. Since repeat dose studies have not been performed under nasal allergen challenge conditions, and proposed labeling includes repeating a dose if symptoms persist, there is residual uncertainty in the PK/PD response following a repeat dose.”
While not bound to the committee’s recommendations, the FDA does take them into consideration when making final decisions on approval. If approved, neffy would be the first needle-free epinephrine product to treat severe allergic reaction. A decision is expected by mid-2023.
Commenting on the vote, Richard Lowenthal, Co-founder, President and CEO, ARS Pharmaceuticals, said, “We believe our clinical data from more than 600 individuals demonstrate neffy’s absorption-enhancing nasal spray technology is comparable to injectable products in delivering potentially lifesaving epinephrine, but with unique advantages of being small, needle-free and conveniently sized. We are committed to making it easier for patients and caregivers to carry and administer epinephrine without the anxiety and hesitation associated with using a needle-based device.”
- 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. News release. May 11, 2023. Accessed May 12, 2023. https://www.globenewswire.com/news-release/2023/05/11/2667468/0/en/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.html.
- FDA briefing document. Pulmonary-Allergy Drug Advisory Committee Meeting. FDA. May 11, 2023. Accessed May 12, 2023. https://www.fda.gov/media/167986/download.