The FDA declined to approve an epinephrine nasal spray (ARS-1, also known as neffy), requesting that an additional premarketing study be conducted, maker ARS Pharmaceuticals announced.
The company is seeking an indication for epinephrine nasal spray as the first non-injectable treatment for type 1 allergic reactions, such as anaphylaxis.
However, in a complete response letter, the FDA said a pharmacokinetic/pharmacodynamic study, assessing repeat doses of the nasal spray compared with repeat doses of an epinephrine injection product under allergen-induced allergic rhinitis conditions, will be needed to support approval -- not as a postmarketing commitment, as previously suggested by the agency.
The FDA's decision goes against the recommendations of its Pulmonary-Allergy Drugs Advisory Committee, which had voted earlier this year in favor of the nasal spray treatment for both adults and children weighing 30 kg (~66 lb) or more, by a 16-6 and 17-5 vote, respectively.
Committee members who voted in favor of the product's approval cited their hope that the approved nasal spray would provide patients and their caregivers more options for allergic reaction treatment, particularly for those who have difficulty administering traditional epinephrine or who have a fear of needles, which can delay crucial care.
The main concern expressed at the time by FDA staff was the lack of clinical efficacy data for ARS-1, as there is no precedent for an epinephrine product that does not require an injection.
"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," said Richard Lowenthal, president and CEO of ARS Pharmaceuticals, 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," he continued.
The manufacturer said it plans to submit a formal dispute resolution request to appeal the FDA's decision. It intends to resubmit the application to the agency, anticipating doing so in the first half of the new year.
"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 said.
In a statement, the Asthma and Allergy Foundation of America (AAFA) said they were "disappointed" by the FDA's move, saying that patients need options.
"In an AAFA study on food allergies in 2019, nearly three out of four people reported not using or receiving a dose of epinephrine during a recent severe allergic reaction," the patient advocacy group noted. "Fear of epinephrine and needle phobia are significant reasons why people are hesitant or delay treatment for a condition that requires immediate action."