EpiPen Alternative: FDA May Approve First Nasal Spray for Anaphylaxis

Anaphylaxis — a potentially life-threatening allergic reaction — is common in the US. It's estimated that up to 5% of people have experienced anaphylaxis.

It is vital to treat severe allergic reactions as quickly as possible and the current treatment involves using a needle-based device like an EpiPen to get an injection of epinephrine.

However, a potential new nasal spray device, known as "Neffy," could soon be used to deliver epinephrine.

An external advisory committee to the Food and Drug Administration (FDA) recently voted in support of the product.

In a statement, ARS Pharmaceuticals, the makers of Neffy, said a final FDA decision is expected by mid-2023.

Study data provided by ARS Pharmaceuticals showed that epinephrine delivered via the nose had a similar influence on heart rate and blood pressure as an injection.

This is crucial, as "during anaphylaxis, heart rate slows down and blood pressure drops, making it difficult to get blood pushed throughout the body to major organs," explained Dr. Manan Shah, co-founder and chief medical officer at Wyndly.

The nasal device proposed for use in delivering epinephrine isn't new to the medical field.

"The Unit Dose Sprayer device utilized to deliver Neffy is the same technology used for medications like Narcan (naloxone)," explained Dr. Jessica Van Acker, a faculty instructor in the Department of Pharmacy Practice at Albany College of Pharmacy and Health Sciences. It's also known as adrenaline.

In addition to tackling reactions in vital organs such as the heart and lungs, "epinephrine also prevents the release of histamine and other chemicals that are responsible for out-spiraling of an allergic reaction," said Dr. Shuba Iyengar, MPH, co-founder and chief medical officer at Allermi.

"It is an invaluable medical treatment for people who have a history of anaphylaxis," she shared with Healthline.

The nasal spray "delivers a fine mist of epinephrine solution into the nasal cavity," explained Iyengar. "The medication [is then] rapidly absorbed through the moist lining of the nasal passages that is lined with blood vessels."

From there, epinephrine enters the bloodstream, where "it binds to specific cell receptors to improve blood flow and reverse the symptoms of a severe allergic reaction," she said.

The good news is that epinephrine gets to work fast. O’Shea said that symptoms start easing within 5-10 minutes after injection into the muscle.

Around 20% of patients require a second dose of epinephrine, and delivery "may be repeated at 5-15 minute intervals if there is no response or inadequate response, or even sooner if symptoms are significantly worsening acutely," O’Shea said.

If you have an allergic reaction that requires epinephrine, you should still go to a hospital for follow-up care even if the initial anaphylaxis symptoms have eased.

The FDA committee reviewed various data relating to the efficacy of the Neffy device and any potential drawbacks.

Several studies, comprising over 600 individuals, were conducted by ARS Pharmaceuticals to compare the effects of epinephrine when delivered via Neffy and EpiPen.

In blood measurements taken 10-20 minutes after administration, epinephrine levels in the body were similar between the two devices. The effects on anaphylactic symptoms were also comparable.

When a second dose of epinephrine was given 10 minutes after the first, Neffy and EpiPen's effects on anaphylaxis were again similar. Some results even showed that the nasal device had a significantly greater influence on blood pressure.

Additionally, none of the studies reported any serious adverse effects following the use of the nasal device.

It was noted, however, that levels of epinephrine in the body declined faster when delivered by nasal spray rather than injection and the committee acknowledged that durability might be a point for future discussion.

There was also some concern over the impact of nasal congestion on epinephrine intake.

While the nasal spray did positively affect anaphylactic symptoms in those with a runny or blocked nose, the FDA report stated that "The Applicant agreed that a second dose is likely needed under nasal edema condition during anaphylaxis."‘

Ultimately, the committee voted in favor of the nasal device product, with 16:6 supporting its use by adults and 17:5 supporting its use by children (weighing over 30 kg).

While the FDA does not have to follow the recommendations or guidance of their committees, it previously stated that this expert advice helps them "make sound decisions based on the available science."

"Many individuals are worried about giving an injection — possibly due to pain or fear of administering incorrectly," shared Dr. Tiffany Owens, an allergist/immunologist at The Ohio State University Wexner Medical Center.

However, "the nasal spray device will be a needleless system, and it will be smaller than auto-injector devices," she told Healthline.

"This may result in more patients carrying their epinephrine devices with them," Owens shared, "and will, hopefully, decrease hesitancy to administer epinephrine."

Previous research shows that 52% of people who qualify for an EpiPen don't use it.

While the nasal spray device offers a promising alternative, Van Acker said it does not eliminate the risk of improper or incorrect use.

"Proper training and counseling should be provided to patients on whatever epinephrine rescue medication they have on hand," she asserted.

This summer experts at the FDA will review the clinical data supplied and determine whether or not to approve the product for public use.

Van Acker believed the outlook was promising. "Based on what we know about epinephrine and data presented to the FDA, I do believe Neffy could be approved for use/sale."

She continued: "Neffy's fast onset of action, side effect profile, and analysis of BMI and drug exposure are compelling pieces of data in support of its approval."

Essentially, it's up to the FDA to determine whether more data is required. Before release for public use, its safety and efficacy needs to be well established.

"I think [the data] is promising, but it hasn't given us quite enough information just yet to draw concrete conclusions," Shah concluded.

"First and foremost, anaphylaxis should be promptly treated with epinephrine," said Dr. Kelly O’Shea, assistant professor in the Department of Internal Medicine at the University of Michigan's Mary H. Weiser Food Allergy Center.

While epinephrine is highly effective in treating severe allergic reactions, what is it, and how does it work?

"Epinephrine is a hormone and neurotransmitter," explained san Van Acker. It's also known as adrenaline.

"[It] works by stimulating alpha-, beta1-, and beta2-adrenergic receptors, which are found throughout the body," she told Healthline.

Stimulating these receptors allows the symptoms of anaphylaxis to be counteracted.

Anaphylaxis is the most severe type of allergic reaction

"[It] typically occurs within seconds or minutes of exposure to an allergen," said Dr. Ruchi Gupta, MPH, professor of pediatrics & medicine at Northwestern University Feinberg School of Medicine and clinical attending at Ann & Robert H. Lurie Children's Hospital of Chicago.

Signs can be mild to begin before quickly developing into more severe symptoms.

"The reaction typically includes more than one body system," Gupta told Healthline. As such, numerous symptoms can occur, ranging from itching and red skin to throat, lips, and tongue swelling, to stomach pain, nausea, and diarrhea.

While nut allergies are commonly associated with anaphylaxis, this isn't the only potential cause.

"You can develop a food allergy to virtually any food," said Gupta. "The most common in the US include peanuts, milk, shellfish, tree nuts, egg, fin fish, wheat, soy, and sesame."

Allergic reactions can also occur after taking medicine, she noted — such as some antibiotics and non-steroidal anti-inflammatory drugs (NSAIDs) like aspirin.

Furthermore, insect stings can also lead to severe reactions, "particularly wasp and bee stings," Gupta shared.

If you think you’re experiencing an anaphylactic reaction, call 911 immediately and — if available — use an epinephrine auto-injector (such as an EpiPen).

"The person experiencing anaphylaxis should lie down on their back," said Van Acker, "and if they are vomiting, they should be turned on their side to prevent choking."

Even if you’re feeling better, you should still go to the emergency room to be properly checked out and monitored.

It's also important to watch for recurring symptoms for a few days after, shared Gupta.

"Symptoms may recur 1 to 72 hours (most within 8 hours) after apparent resolution of the initial phase," she revealed.