A needle-less alternative to EpiPen has FDA approval. Will doctors prescribe it?

A potentially ground-breaking nose-spray version of the drug epinephrine will soon hit the market — an alternative to auto-injectors like EpiPen for people having serious allergic reactions. The drug was approved this month by the FDA for use in adults and older children.

But some allergists say they’re not in a hurry to prescribe it.

Although the new needle-less option, called neffy, has the potential to provide a cheaper, less painful, and more convenient option than the EpiPen, experts say, studies have not yet been done on people who are in the throes of life-threatening allergic reactions, known as anaphylaxis. That raises concerns about whether the drug is effective enough to trust for people with serious allergies.

“We’re very excited about this development but we do have serious concerns,” says Dr. Robert Wood, director of Johns Hopkins Children’s Center’s Division of Allergy, Immunology and Rheumatology, and a Johns Hopkins professor of pediatrics.

Anaphylaxis, also known as anaphylactic shock, is a severe, sometimes life-threatening allergic reaction that comes on quickly with symptoms such as shortness of breath, hives, a drop in blood pressure and a loss of consciousness in response to triggers such as foods, insect bites or medicines that a person is allergic to.

Epinephrine is the only life-saving treatment for anaphylaxis and has previously only been available to patients as an injection. Use of epinephrine for the treatment of severe allergic reactions has been in needle-based form since the FDA approved it in 1939. EpiPen, which is the most well-known brand of auto-injector that a person can use on their own, has been around since the 1970s. A generic version became available in 2018.

Needle substitute

Neffy is the first alternative to injectable epinephrine. In clinical trials, drugmaker ARS Pharmaceuticals found the nasal spray is safe and delivers the same amount of epinephrine to the bloodstream as an auto-injector. The FDA approved the spray on Aug. 9 for the emergency treatment of allergic reactions including anaphylaxis in adults and kids who weigh more than 66 pounds.

There are reasons to be excited about an epinephrine nasal spray, says Dr. J. Andrew Bird, a pediatric allergist at UT Southwestern and director of the Food Allergy Center at Children’s Medical Center in Dallas.

It may be easier to tolerate for adult patients who are hesitant to self-inject and for parents who are squeamish about injecting their kids.

Neffy — which is about the size of half an iPhone and fits easily in a pants pocket — is also handier to carry than an EpiPen, says Bird. That alone could increase compliance and adherence to epinephrine use among people with dangerous allergies.

As it stands, only about 40% of the highest-risk patients actually carry their auto-injectors, according to a 2023 study, which surveyed adults and kids with severe allergic reactions and their caregivers. Participants listed inconvenience and forgetfulness as the top reasons they didn’t carry their EpiPens, along with a belief that they could successfully avoid the things they’re allergic to.

Dr. Karen Kaufman, a doctor of osteopathic medicine in private practice in Vienna, Va., and a fellow of the American Academy of Allergy, Asthma and Immunology, says she thinks neffy will soon replace auto-injectors in public spaces like schools and airplanes because the product is smaller and easier to store.

Among its other potential benefits — Neffy lasts longer than autoinjectors, with a shelf life of two years instead of 12 to 18 months for the EpiPen, according to San-Diego based ARS, which developed neffy over the last eight years. The company also says neffy can be left in the heat and the cold for months at a stretch, while EpiPens must be kept at room temperature or they degrade. And neffy is easy to use without any training required.

Neffy might be easier to administer correctly, adds Richard Lowenthal, co-founder, president and CEO of ARS. Operator errors can happen with auto injectors, according to Mylan, the company that makes the EpiPen. One dangerous mistake is injecting epinephrine into a blood vessel instead of into muscle. This can cause a stroke, heart arrhythmia, or heart attack. By contrast, there’s no danger if there are operator errors with neffy, Lowenthal says, adding that ARS found no harm to the eyes if the user accidentally squirts the medicine into them.

Untested concerns

But neffy also raises concerns among prescribing physicians. One worry, Wood says, is that it hasn’t been tested in people actually undergoing anaphylactic reactions because researchers can’t ethically trigger a potentially deadly allergic reaction and then give a patient a placebo. When someone is having a severe allergic reaction, he says, the nasal cavity can become blocked. That might stop absorption of the drug and let a serious allergic reaction continue unabated, Wood says.

ARS pharmaceuticals did do a small open label study in Japan. They used food to trigger allergic reactions in 15 people with specific food allergies. All had allergic reactions, three of which were serious, and everyone got the drug. The company says neffy brought relief to each participant within five minutes, which is similar to what an epinephrine autoinjector does.

Insurance coverage is another unknown. Lowenthal says ARS is working with the big insurance companies to get neffy on their lists of approved drugs, which could take about six months. He says the company plans to make a two-pack of the spray available for prices that will vary depending on a person’s means but are generally comparable to the cost of auto-injectors.

The price of the EpiPen has been controversial since Mylan acquired the rights to produce it in the U.S. in 2007 and increased the price by 600%. On average retail prices for EpiPen range from $650 to $750, without insurance according to GoodRx. A generic version costs between $150 and $200.

Other alternatives to epinephrine auto injectors are also in the works. Nasus Pharma of Tel Aviv-Yafo, Israel, is working on an epinephrine powder that goes in the nose, and New Jersey-based Aquestive Therapeutics has an epinephrine-laced film that goes under the tongue and is in late-stage trials. ARS says it is developing a nasal spray for smaller children.

For now, doctors say they may avoid prescribing the new spray just after it hits the market, in part because they would need to devote employee hours to getting on the phone to press insurance companies to cover it just like with any new medication, says Kaufman.

Once neffy becomes available — likely in late September, according to Lowenthal — Wood says he is willing to prescribe it to patients who ask for it, but he’ll suggest they also keep an auto-injector handy just in case.

Then, he says, he’ll wait for reports to come in about how neffy performs. If the spray does as well as auto injectors to stop dangerous allergic reactions to food, drugs or insect bites, then yes, Wood says it actually could become a game changer. “I would have confidence in it then,” he says.