Hr Pharmaceuticals, Inc – FDA CRL

The U.S. Food and Drug Administration (FDA) issued a Complete Response Letter to ARS Pharmaceuticals, Inc. regarding its New Drug Application (NDA 214697) for Neffy (epinephrine nasal spray). The application, submitted under section 505(b)(2) of the Federal Food, Drug, and Cosmetic Act on August 19, 2022, and amended in May and June 2023, sought approval for treating allergic reactions, including anaphylaxis, in adults and pediatric patients weighing 30 kg or more. The FDA determined it could not approve the NDA in its current form due to two main areas of concern. First, in Clinical/Clinical Pharmacology, the agency found insufficient evidence of effectiveness under real-world conditions. While initial blood pressure remained comparable, epinephrine plasma concentration and pulse rate from Neffy dropped below the comparator after 20 minutes in subjects with allergen-induced acute rhinitis. The FDA requires additional pharmacokinetic/pharmacodynamic (PK/PD) data from repeat-dose trials in subjects with allergen-induced acute rhinitis, comparing Neffy to epinephrine injections, and assessing administration in both nostrils to demonstrate durability and effectiveness for patients needing a second dose. Second, regarding Product Quality, the application lacked necessary information concerning Nitrosamine Drug Substance-Related Impurities (NDSRIs), specifically N-nitroso-epinephrine. ARS Pharmaceuticals must conduct a risk assessment and, if necessary, provide confirmatory testing data from multiple batches to ensure NDSRI levels are below acceptable intake limits throughout the product's shelf-life. If levels exceed limits, the company must investigate the root cause and implement manufacturing changes, or provide a justified alternative acceptable intake limit. The FDA reserves comments on proposed labeling until these deficiencies are resolved.