September 20, 2023
The U.S. Food and Drug Administration (FDA) has delayed approval of a new epinephrine nasal spray called neffy®. The device was developed by ARS Pharmaceuticals. Here is a statement released by Allergy & Asthma Network:
Allergy & Asthma Network is very disappointed that the U.S. Food and Drug Administration (FDA) has delayed approval of a new epinephrine nasal spray, the product developed by ARS Pharmaceuticals. The epinephrine nasal spray, branded as neffy®, would be a new treatment option for people with severe or life-threatening allergies who prefer a needle-free way to treat anaphylaxis. Unfortunately, FDA’s decision could delay this product from reaching the public for at least a year, if not longer. ARS Pharma is now required to conduct additional research into the product, even though the FDA’s Pulmonary-Allergy Drugs Advisory Committee already voted 16-6 in favor of its use in adults and 17-5 in favor of its use in children.
As a patient advocacy organization, Allergy & Asthma Network will seek to better understand the reasons for the agency’s decision to delay approval. While epinephrine auto-injectors remain a reliable treatment for many people with severe or life-threatening allergies, we have heard from many patients and families who feel hesitant about injecting themselves with needle-based epinephrine. Seconds count when someone is experiencing anaphylaxis and any delay in treatment could have life-threatening consequences. A needle-free epinephrine option will address an unmet need – and it’s needed sooner rather than later.
Allergy & Asthma Network will continue to advocate for an epinephrine nasal spray treatment with FDA and keep our community informed about this important issue. We support ARS Pharma’s commitment to bring this new treatment option to millions who will benefit from it.
On Sept. 19, 2023, FDA sent ARS Pharma a Complete Response Letter (CRL) delaying approval of neffy. In the letter, FDA requested completion of an additional study. The study is intended to evaluate repeat doses of the epinephrine nasal spray compared to repeat doses of an epinephrine auto-injector.
ARS Pharma plans to submit a Formal Dispute Resolution Request to appeal the CRL.
What is the new timeline for a possible neffy approval? ARS Pharma expects to resubmit its application to FDA in the first half of 2024. This would position the epinephrine nasal spray for FDA approval in the second half of 2024.
For now, the first line of treatment for anaphylaxis remains using an epinephrine auto-injector. These needle-based devices were first approved by FDA in 1987. Since then, epinephrine auto-injectors have become the standard treatment for anaphylaxis.
An epinephrine nasal spray would offer a new treatment option for people who prefer a needle-free way to treat anaphylaxis.
FDA Advisory Panel Recommended neffy for Approval
The FDA decision to delay approval of the epinephrine nasal spray comes after its advisory committee recommended the device for approval. At a public meeting on May 11, 2023, the FDA’s Pulmonary-Allergy Drugs Advisory Committee voted 16-6 in favor of the epinephrine nasal spray for use in adults. The committee also voted 17-5 in favor of its use in children.
As part of its initial New Drug Application to FDA, ARS Pharma submitted four clinical trials. Its research involved 600+ adults and children who weighed 66 pounds or more. Data has shown similar epinephrine levels in the body from both the nasal spray and the auto-injector, including during self-administration and in children. Overall, the nasal spray was shown to be well tolerated. Side effects were mild and did not include nasal problems.
Some members of the FDA advisory panel expressed concern with data comparing the effects of the epinephrine nasal spray with the auto-injector. The data showed a lower amount of epinephrine in the body for the first 10 minutes after using nasal epinephrine compared to the injection. This delay of full effect could be critical for someone experiencing a life-threatening allergic reaction.
Other members had concerns whether the presence of nasal congestion could reduce the effects of the epinephrine nasal spray. A second dose of epinephrine may be needed in this case.
Epinephrine nasal sprays are expected to be easier to carry and use than auto-injectors. Many people with anaphylaxis and caregivers tend to hesitate when using auto-injectors, in part because of worries about injecting a needle. Studies show any hesitation or delay in administering epinephrine puts patients at risk for worse outcomes, and even death.
“Additional safe and effective treatment options like neffy will offer patients new choices that are currently not available,” says Allergy & Asthma Network Director of Advocacy Charmayne Anderson. “We want to see more safe and effective epinephrine options for people at risk for anaphylaxis so they will be able to get the treatment they need when they need it.”
Anderson was among patient advocates who offered testimony at the FDA advisory panel public meeting on May 11, 2023. Read her full comments below.
More Epinephrine Treatments On the Horizon
Neffy is not the only epinephrine nasal spray in development.
Bryn Pharma is also developing an epinephrine nasal spray – brand name is UTULY™. The company reported positive data of UTULY in a poster presented at the 2023 American Academy of Allergy, Asthma & Immunology (AAAAI) meeting in San Antonio.
Bryn Pharma clinical trials also compared UTULY’s effectiveness to an auto-injector. The studies found the epinephrine nasal spray reached similar levels of epinephrine absorption in the body as the auto-injector. Researchers also reported the nasal spray was safe and well tolerated, and side effects were mild.
It’s clear that patients and families want an efficient epinephrine delivery device that does not involve needles. In 2018, Allergy & Asthma Network recruited patients and caregivers for a study sponsored by StellaPharma (now StellaPharm). The study examined preferences for nasal spray epinephrine. Researchers surveyed 372 patients and caregivers overall.
- 91% of study participants would consider using an epinephrine nasal spray instead of an auto-injector;
- nearly 72% would prefer using an epinephrine nasal spray instead of an auto-injector;
- 82% would prefer needle-free epinephrine instead of an injection;
- 80% would be more likely to carry a smaller and easier to conceal epinephrine product.
- 43% disliked the idea of injecting a needle to administer epinephrine.
In addition to an epinephrine nasal spray, an under-the-tongue (sublingual) strip containing epinephrine is in development. The strip, called Anaphylm™, was developed by Aquestive Therapeutics. It is currently undergoing clinical trials.
The strip is similar in size to a postage stamp. It dissolves under the tongue on contact. It can be carried safely in your pocket.
Remarks from Director of Advocacy Charmayne Anderson at FDA Hearing
Pulmonary-Allergy Drugs Advisory Committee Meeting
U.S. Food and Drug Administration
Docket number is FDA-2023-N-0984
May 11, 2023
Allergy & Asthma Network, the leading national nonprofit dedicated to improving the health of people with allergies, asthma and related conditions, is pleased to provide comments on neffy®, the new epinephrine nasal spray under review by the U.S. Food and Drug Administration (FDA). We are encouraged by this new treatment option, as epinephrine is the primary therapy to treating anaphylaxis, a life-threatening allergic reaction.
Approximately 20 million Americans, including 4 million children, live with food allergies. Up to 50 million people in the United States have experienced anaphylaxis to food, insect venom, medication and latex.
Anaphylaxis is estimated to cause 500 to 1,000 deaths annually. Epinephrine is the first-line treatment when a person is experiencing a life-threatening allergic reaction.
Prevalence and burden of severe allergies is growing for millions of Americans. Anaphylaxis is a distressing and potentially fatal event. Avoidance alone is simply not enough. One systematic review showed 12.28 cases of accidental peanut exposure per 100 person-years of children/adults with peanut allergy. They live in constant fear of an accidental exposure, impacting their quality of life. These are not nameless, faceless statistics. These are real people with families, hopes, dreams and fears.
A tragic example of this is the death of 3-year-old Elijah-Alavi Silvera. His father Thomas, from New York City, suffered every parent’s nightmare in 2017 when Elijah died from a severe allergic reaction while at preschool. Even though Thomas and his wife took great strides in making sure his childcare providers were aware of Elijah’s food allergy and prepared to administer epinephrine, an accidental exposure occurred and there was a delay in using Elijah’s auto-injector. Within minutes, Thomas’s world was turned upside down. His family will never be the same.
Access to epinephrine is critical, yet innovation has been lacking. The first epinephrine auto-injector came on the market in 1987. Vial and syringe or auto-injectors are still the only option for treating anaphylaxis.
Data further shows that death from anaphylaxis occurs more often when there is either a delay in administering epinephrine or it is not given at all. Studies have shown that auto-injectors are often not carried or not used promptly. The causes of the delay vary, from needle phobia to hesitation using the auto-injector to reluctance to carry due to the size of the auto-injector devices.
Allergy & Asthma Network advocates for innovative therapies to address specific medical needs and improve patients’ lives. We believe individuals and caregivers should have access to safe and effective epinephrine products that encourage individuals to carry it with them and not hesitate to use it promptly in an allergic emergency.
We are optimistic about the continued advancements in scientific research and development of treatments for anaphylaxis, which include needle-free nasal sprays like neffy® and sublingual (under the tongue) administration that give people additional treatment options. These are smaller-size alternatives for those who are reluctant to use or carry an auto-injector.
The need and patient preference for new anaphylaxis treatment options are further underscored in the Voice of the Patient Report that followed the 2021 externally-led Patient-Focused Drug Development Meeting (PFDD). This meeting was organized by the Food Allergy Collaborative, a coalition of eight food allergy organizations, people living with food allergies, industry partners and FDA. The Report highlights patients and caregivers who want less-invasive options in epinephrine treatment.
People with severe allergies are relying on the FDA to ensure innovative products that are safe and effective to reach the community they can help the most. Innovation without access only breeds frustration. Quality of life considerations and patient preferences should play a key role in driving treatment decisions for people, especially those with food allergy.
Additional safe and effective treatment options like neffy® will offer patients new choices that are currently not available. We want to see more safe and effective epinephrine options for people at risk for anaphylaxis so they will be able to get the treatment they need when they need it.
Thank you for your consideration of our comments and the integral role you serve today to end the needless death and suffering due to severe, life-threatening allergies.
Purvi Parikh, MD, FACAAI is an adult and pediatric allergist and immunologist at Allergy and Asthma Associates of Murray Hill in New York City. She is on faculty as Clinical Assistant Professor in both departments of Medicine and Pediatrics at New York University School of Medicine.