FDA refuses to okay first nasal spray for allergic reactions, firm says

Federal regulators refused to approve an epinephrine nasal spray that would have been the first needle-free treatment for serious allergic reactions triggered by certain foods, insect stings and medications, the manufacturer said late Tuesday.

San Diego-based ARS Pharmaceuticals said in a news release that it had received “a complete response” letter from the Food and Drug Administration asking the company to conduct an additional study to support approval of the two-milligram nasal spray, named Neffy. The spray is designed to block allergic reactions — including a life-threatening condition called anaphylaxis, which causes a constriction of the airways, plummeting blood pressure and a racing pulse.

The company expressed disappointment about the FDA’s action and said it would file an appeal with the agency over the decision.

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“We are very surprised by this action and the late requirement” for additional research before approval, said Richard Lowenthal, president and chief executive of ARS Pharmaceuticals.

The company also said it would conduct the requested study and resubmit its application to the FDA in the first half of next year in hopes of securing an approval in the second half of 2024.

The FDA does not publicly release complete response letters, which explain to companies why their applications were not approved and often contain proprietary information. Such rejections don’t rule out future approvals, once the agency’s outstanding questions are resolved.

But the decision on Neffy represents at least a temporary setback for ARS.

ARS shares plunged by 56 percent Wednesday to $2.92, less than half what they were worth when the company went public through a merger in November.

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Currently, epinephrine is administered only by needle — either as part of an auto-injector device, such as EpiPen, or a syringe. ARS had pitched Neffy as a superior alternative to the EpiPen, citing research that many people with severe allergies don’t carry their injector devices or delay using them because of fear of needles.

“This reluctance to use needle-based injection devices in a timely manner is often driven by fear,” Lowenthal said in a July 2022 call when the company went public, according to a transcript compiled by S&P Global Market Intelligence. “Neffy is needle-free,” he said. “It’s small and easy to use.”

Tim Lugo, an analyst at financial firm William Blair, called the FDA’s decision surprising.

“It does raise questions of whether the agency really wants to approve the therapy,” he wrote in a research note Wednesday, adding that “regulators look to be holding neffy to a much higher standard than comparable products.” Earlier, he had predicted Neffy was likely to be approved and become “a major player in the U.S. epinephrine market,” with peak sales of $750 million.

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An ARS board member bought company shares in late August for about $23 million, signaling confidence that the stock price would increase.

In May, the agency’s outside experts, the Pulmonary-Allergy Drugs Advisory Committee, voted in favor of Neffy, concluding that data presented by ARS showed the benefits of the product outweighed the risks. The vote was 16-6 in favor of approving the drug for adults and 17-5 for children 66 pounds and over. The FDA usually follows the advice of its outside advisers but is not required to do so.

But the advisory committee also acknowledged uncertainty surrounding the product because of a lack of clinical data. Epinephrine has been used for more than a century, before the FDA existed, and has never undergone the agency’s rigorous process to prove safety and effectiveness.

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Rather, extensive use of epinephrine over decades has shown it is effective in treating allergic reactions. Doctors and ethicists say it would be unethical to provoke a potentially dangerous anaphylactic reaction to test a new product. Severe allergic reactions can be triggered by foods such as peanuts, bee stings and some medications.

ARS has said it submitted information to the FDA showing that Neffy delivered a level of epinephrine consistent with the auto-injector devices and that the way the drug acted in the body was similar to or better than what is seen with those devices.

The company said in its statement Tuesday that the FDA has asked for more research assessing repeat doses of Neffy compared with repeat doses of an injection product. Lowenthal said the FDA previously had indicated that such a study could be conducted after approval.

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In late June, the FDA postponed its decision deadline for Neffy by three months to Sept. 19, telling the company that it needed more time to complete its review. At the time, the company said the agency was “working on labeling and post-marketing commitments as the final steps in the review process.”

Eric Karas, ARS Pharmaceuticals’ chief commercial officer, predicted last year that Neffy would “make the current needle injectors as dated a technology as the flip phone is today.”

In June, Viatris, the company that makes EpiPen, disagreed, filing a citizen petition asking the FDA to require ARS Pharmaceuticals to conduct more studies. Viatris was formed in 2020 by the merger of Mylan and Upjohn.

“We have followed Neffy or this intranasal product very closely from the science perspective and actually have some concerns,” Rajiv Malik, president of Viatris, said in an August earnings call. “We have raised our voice to highlight those concerns to FDA.”

ARS Pharmaceuticals, which created Neffy, brought together many veterans who developed Narcan, the nasal spray used to revive people from opioid overdoses.

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