The Food and Drug Administration on Tuesday declined to approve Neffy, an epinephrine nasal spray from drugmaker ARS Pharmaceuticals, keeping the first needle-free option for Americans to treat serious allergic reactions off the market while it waits for more data. ‘tests.
The ARS expected the FDA to approve Neffy for use in adults and children weighing more than 30 kilograms, or about 66 pounds. The spray would have required a prescription, like EpiPens and other epinephrine injections currently used to treat anaphylaxis.
Epinephrine is crucial in emergencies to treat life-threatening allergic reactions. The new spray, if ultimately approved, would be a welcome alternative for many families of children with severe allergies who prefer to avoid needles.
According to ARS, FDA regulators decided Tuesday that more data is needed to evaluate the safety of repeated doses of the nasal spray before it can be approved. FDA advisers had suggested in previous guidance issued in May that the additional data could be collected in a trial after the drug hits the market. The drugmaker therefore expressed its disappointment with Tuesday’s decision.
“We are very surprised by this action and by the late requirement to change the repeated dose study from a post-marketing requirement, on which we had previously aligned with the FDA, to a pre-approval requirement, in especially given the positive review. committee vote,” ARS Pharma co-founder, president and CEO Richard Lowenthal said in a statement Tuesday evening. “We are deeply disappointed that this action will further delay the availability of neffy for the millions of people who are at risk of developing a serious, life-threatening allergic reaction. Patients and caregivers wait neffyand we aim to complete the newly requested trial as quickly as possible to meet patient needs.
“Major barriers limit the rapid use of epinephrine in a community setting. Many patients fear needles and many are uncomfortable with self-injection. There is also the inability to transport the devices currently available,” Lowenthal told a panel of external FDA advisors. at a meeting in May to weigh the product.
Lowenthal told the committee the company plans to provide the product in a “fine neffy carrying case” each containing two sprays.
Up to 85% of patients with severe allergies would be willing to carry epinephrine with them daily if Neffy were an option, Lowenthal said, according to their surveys, compared to about 55% with current options.
“If they don’t have it with them, it’s moot. They don’t give birth, they don’t have medicine, they go to the hospital,” Lowenthal said in May.
The drugmaker says Neffy nasal spray works by delivering a dose of epinephrine to patients experiencing allergy attacks using two other technologies already used in other FDA-approved products. One is the substance dodecylmaltoside, licensed by drugmaker Neurelis, which it says “enhances drug absorption” through the mucous membranes, which are cells that line the airways from the nose to the lungs. Neurelis used this ingredient, under the brand Intravail, in its own spray to treat epilepsy.
The other is a sprayer sold by Aptar Pharma and already used in many products. This is the same type of sprayer used by Narcan brand naloxone nasal sprays, which are used to treat drug overdoses and recently received the green light from the FDA for over-the-counter sales.
Despite the availability of some generic alternatives, some Americans continue to face high prices for annual purchases of currently available epinephrine injection devices. The brand name EpiPen and its generic alternatives can cost some families more than $200 a year, leading some states to consider capping epinephrine prices.
Other epinephrine nasal sprays are also in the works. Drugmaker Bryn Pharma has touted promising results from its experimental epinephrine nasal spray Utuly, which it says could outperform current injectors.
Is it as effective as an injection?
The FDA’s rejection of Neffy pending more trial data is just the latest delay in the ARS’ attempt to bring the drug to market.
The company previously said the FDA could decide whether to approve Neffy by mid-2023. But ARS revealed in June that the FDA had told the company it would need by September to decide on approval. The additional time was needed to complete “discussions on labeling and post-marketing commitments” raised after the FDA advisory committee meeting on Neffy, the company said.
A majority of members of the FDA’s Pulmonary Allergy Drug Advisory Committee ended up voting in May to support that neffy’s benefits outweighed its risks, after wrestling with a number of questions about whether the spray may be less effective than current injections.
“Following the strong approval of our clinical data on Neffy at the PADAC meeting in May, we had limited time to answer final questions and complete the labeling,” Lowenthal said in a statement.
Although epinephrine is widely recognized by experts as effective in treating severe allergic reactions, the use of this chemical – purified adrenaline which dates back to the early 20th century – predates the existence of the FDA . This means that the initial use of epinephrine to treat anaphylaxis occurred without clinical trials to directly prove its effectiveness, as well as to better understand what measurements of the drug in the body are necessary for it to be effective.
The original EpiPen was approved in 1987 without clinical trials or detailed data on how the drug is absorbed or its effects on the body, the FDA says.
Clinical trials to prove that administering epinephrine as a spray works as well as an injection would be difficult to conduct ethically, FDA officials acknowledged.
Instead, ARS Pharmaceuticals conducted various studies to generate so-called “surrogate” data aimed at determining whether its spray could be as effective as the injections.
These included dosing subjects exposed to seasonal allergens, as well as measuring concentrations of the drug in their bodies, which generated conflicting data. Comparisons with measurements of epinephrine injections also led to varied results.
“I really want this product to work. I mean, we definitely benefit from a needle-free means of cob delivery. And I think the sponsor has done a good job trying to find that balance. That said, I think we use low surrogate data to make sure of that,” FDA committee member Lewis Nelson said at the May meeting.
Nelson echoed other committee members in praising the company and FDA’s approach to resolving some of the substantial variabilities seen with other epinephrine injections. But he also said he believed more data would be needed to approve the drug.
“I would really hate to learn, without better clinical data, that we are recommending approval of a product based on surrogate data that is inconsistent and somewhat confusing and, ultimately, because of that, patients are being harmed,” he said at the meeting.