The FDA issued the Complete Response Letter (CRL) based on the request for a completed pharmacokinetic/pharmacodynamic study to assess how repeat doses of the epinephrine nasal spray compare to repeat doses of an epinephrine injection product. ARS Pharma is set to file a Formal Dispute Resolution Request to appeal the CRL.
On Tuesday, September 19, 2023, the FDA issued a Complete Response Letter (CRL) to ARS Pharmaceuticals, Inc. regarding its New Drug Application (NDA) for neffy, a needle-free epinephrine option to treat type 1 allergic reactions, including anaphylaxis for adults and children weighing more than 66 lbs (30 kg).1
If approved, neffy would have been the first-ever needle-free nasal spray epinephrine to treat people with severe allergic reactions. According to a press release from ARS Pharma, the FDA requested the completion of a pharmacokinetic/pharmacodynamic study to assess repeat doses of neffy compared to repeat doses of an epinephrine injector.1
ARS Pharma intends to submit a Formal Dispute Resolution Request (FDRR) to appeal the CRL. The manufacturer stated it “previously agreed with the FDA to conduct a repeat-dose study under allergen-induced allergic rhinitis conditions as a post-marketing commitment,” and that the company and the FDA previously aligned on final physician’s labeling and to complete this study as part of a post-marketing requirement. The manufacturer plans a resubmission to the FDA in the first half of 2024, in anticipation for a new FDA action date in the second half of 2024.1
"Clearly this is disappointing news for those at risk for life-threatening allergic reactions and their caregivers," said Theresa Bingemann, MD, associate professor of pediatrics and medicine, program director, Allergy and Immunology Fellowship, University of Rochester School of Medicine and Dentistry. "However, second doses are needed in a third of anaphylaxis cases, and allergic reactions can be life-threatening. Confidence in the data for scenarios in which a second dose is needed is critically important."
The issuance of a CRL comes after the FDA’s Pulmonary-Allergy Drug Advisory Committee (PADAC) voted in support of a favorable benefit-risk profile for neffy in May 2023. The PADAC voted 16 to 6 in favor for adults and 17 to 5 in favor for children under 18 years weighing over 66 lbs.2
“We are very surprised by this action,” said Richard Lowenthal, co-founder, president, and CEO, ARS Pharma. “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.”1
The company previously announced neffy demonstrated comparable epinephrine levels in the blood compared to injection in clinical trials, including the first 10 to 20 minutes. At 1 minute after dosing, neffy demonstrated comparable or greater pharmacodynamic response compared to intramuscular injection, and comparable safety to injection, without needle-related risks. Adverse events reported in clinical trials were “generally mild in nature without any meaningful nasal irritation or pain, without needle-related risks.”2