The offering covers the emergency treatment of severe type I allergic reactions in children and adults weighing 30 kg (66 pounds) or more. The company initially set an anticipated target action date of mid-2023 for its PDUFA (Prescription Drug User Fee Act).
ARS Pharmaceutical developed neffy with the Neurelis Intravail transmucosal absorption enhancement technology. Intravail enhances drug absorption through the nasal mucosa. This enables the noninvasive delivery of protein, peptide and small-molecule drugs.
The FDA in December 2022 accepted a new drug application (NDA) for neffy. However, its CRL requested the completion of a pharmacokinetic/pharmacodynamic study assessing repeat doses. The agency wants to compare neffy to repeat doses of an epinephrine injection product under allergen-induced allergic rhinitis conditions.
ARS Pharmaceuticals said the FDA requires the additional testing to support approval. However, in May, an FDA Advisory Committee recommended neffy’s approval without the need for additional studies. The panel voted 16:6 on a favorable benefit-risk profile for neffy for adults, plus 17:5 in favor of use for children. ARS says no members of the committee raised specific concerns about the result of a completed study in people with allergen-induced acute rhinitis with single-dose neffy.
The company also said it aligned with the FDA last month on final physicians’ labeling and a post-market requirement to conduct the study as informative for labeling.
The company plans to submit a formal dispute resolution request to appeal the CRL.
ARS Pharmaceuticals CEO caught off-guard by FDA’s decision
Richard Lowenthal, ARS Pharmaceuticals co-founder, president and CEO,
“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. 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,” said Lowenthal. “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 explained that, if approved, neffy would represent the first-ever needle-free nasal spray epinephrine treatment for people with severe allergic reactions. Features include easy carrying and administration, “without anxiety or hesitation.” That proves critical in stopping disease progression, Lowenthal says.
He cited “tremendous” support from patient, advocacy and physician communities in favor of the needle-free treatment. Lowenthal expressed disappointment at the delay in bringing neffy to people at risk of allergic reactions.
“Patients and caregivers are waiting for neffy, and we aim to complete the newly requested trial as quickly as possible to meet the needs of patients.”
The next steps for neffy
ARS Pharma already agreed to conduct a repeat-dose study under the FDA’s terms in a post-market setting. It plans to resubmit in the first half of 2024 and anticipates an FDA action in the second half of the year.
The company says it expects to have cash on-hand of approximately $195 million at the time of an anticipated launch.
FDA’s CRL requested additional information on nitrosamine impurities, asking for testing based on new draft guidance. It issued that guidance after the neffy NDA submission. ARS said it doubts the additional testing would limit its resubmission to the agency.
The company also has neffy under review by regulatory authorities in Europe for human use. It expects an opinion by the end of 2023, followed by additional submissions in other geographies in 2024.
