FDA declines to approve Neffy epinephrine nasal spray for severe allergic reactions

The Food and Drug Administration on Tuesday did not approve Neffy, an epinephrine nasal spray from drugmaker ARS Pharmaceuticals, keeping the first needle-free option for Americans to treat severe allergic reactions off the market pending more trial data.

ARS had expected the FDA to approve Neffy for use in adults and children weighing more than 30 kg, or about 66 pounds. The spray would have required a prescription, similar to EpiPens and others epinephrine injections which is currently used to treat anaphylaxis.

Adrenaline is essential in an emergency to treat potentially life-threatening conditions allergic reactions. The new spray, if eventually approved, would be a welcome alternative for many families with children with severe allergies who would rather avoid needles.

According to ARS, FDA regulators decided Tuesday that more data were needed to assess the safety of repeated doses of the nasal spray before it could be approved. Some FDA advisers had suggested at an earlier meeting in May that additional data should not be collected in a trial after the drug was brought to market, so the drugmaker expressed disappointment with Tuesday’s decision.

“We are very surprised by this action and the late request at this time to change the repeated-dose study from a post-marketing requirement, which we had previously accommodated to the FDA, to a pre-approval requirement, especially given the positive advice Committee vote,” ARS Pharma co-founder, president and CEO Richard Lowenthal said in a statement late Tuesday. “We are deeply disappointed that this action further delays the availability of neffy for the millions of people at risk of a potentially life-threatening severe allergic reaction. Patients and relatives are waiting neffyand we aim to complete the newly requested trial as soon as possible to meet patients’ needs.”

“Major barriers limit the rapid use of epinephrine in a community. Many patients fear needles and many are not comfortable with self-injection. There is also the impracticality of carrying the currently available devices,” Lowenthal told a panel of FDA external advisers at the meeting in May to weigh the product.

Lowenthal told the committee that the company planned to ship the product in a “slim Neffy carrying case” that carries two syringes each.

As many as 85% of patients facing severe allergies would be willing to carry epinephrine with them daily if Neffy were an option, Lowenthal said, their studies suggested, up from about 55% with current options.

“If they don’t have it with them, it’s a moot point. They don’t deliver, they don’t have medicine, they take to the hospital,” Lowenthal said in May.

The drug manufacturer say Neffy Nasal Spray works by delivering a dose of adrenaline to patients facing allergy attacks using two other technologies already used in other FDA-approved products. One is the drug dodecylmaltoside, licensed from drugmaker Neurelis, which it says “enhances drug absorption” through mucous membranes, which are cells that line the airways from the nose to the lungs. Neurelis has used this ingredient, labeled as Intravailin their own spray to treat epilepsy.

The other is one syringe device sold by Aptar Pharma, which is already used in a number of products. It is the same type of syringe used by Narcan-brand naloxone nasal spraywhich is used to treat drug overdoses and var recently given the green light by the FDA for over-the-counter sales.

Despite the availability of some generic alternatives, some Americans continue to experience high price tags for annual purchases of the currently available adrenaline injection devices. The brand name EpiPen and its generic alternatives can cost some families more than $200 a yearwhich has led some states to explore caps on epinephrine prices.

More adrenaline nasal sprays are also on the way. Drug manufacturer Bryn Pharma has announced promising results from its experimental epinephrine nasal spray Utuly, which it says could outperform current injectors.

Questions of efficiency

The FDA’s request for more data was just the latest delay for ARS’ bid to bring the drug to market.

The company had previously said that the FDA could decide on approval of Neffy in mid-2023. But ARS revealed in June that the FDA had told the company it would need until September to decide on the approval. The extra time was needed to complete “labeling and post-marketing commitment discussions” raised after the FDA advisory committee meeting on Neffy, the company said.

ONE majority of the FDA’s Pulmonary Allergy Medicines Advisory Committee ended up voting in May to support the product’s benefits outweighing its risks, after grappling with a number of questions about whether the spray may be less effective than current injections.

“After the strong approval of our clinical data for neffy at the PADAC meeting in May, there was limited time to address any final issues and complete labeling,” Lowenthal said in a release.

While adrenaline is widely accepted by experts as effective in treating severe allergic reactions, use of the chemical – purified adrenaline that dating back to the beginning of the 20th century — predates the FDA’s existence. This means that epinephrine’s original use to treat anaphylaxis occurred without clinical trials to directly prove that it works, as well as to better understand what measurements of the drug in the body are required 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, FDA say.

Clinical trials to prove that delivering adrenaline as a spray works as well as an injection would be difficult to conduct ethically, FDA officials acknowledged.

Instead, ARS Pharmaceuticals operated a various studies to generate so-called “surrogate” data aimed at finding out whether its spray was likely to be as effective as injections.

These included dosing people exposed to seasonal allergens as well as measuring concentrations of the drug in their bodies, which generated some conflicting data. Comparisons with measurements from epinephrine injections also led to different results.

“I really want this product to work. I mean, we definitely benefit from a needle-free means of delivering epi. And I think the sponsor has done a good job of trying to strike that balance. When it That said, I think we’re using weak surrogate data to protect ourselves,” Lewis Nelson, a member of the FDA committee, said at the May meeting.

Nelson echoed other committee members in praising the company and the FDA approach to solution some of the significant variations 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 some 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 harmed,” he said at the meeting .

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