2024’s critical needle-free approvals for pediatric anaphylaxis, influenza | Image Credit: © Aquir - © Aquir - stock.adobe.com.

In the pediatric population, it is no secret that needle phobia can have an impact on the administration of routine vaccines, injections to prevent allergic reactions, and intravenous uses for blood work.

According to the American Academy of Pediatrics, at least two-thirds of children have a fear of needles, which isn’t just a pediatric fear, as nearly a fourth of adults also have the phobia.¹

While there have been long-standing practices to help children get through the challenges of a needle, vaccine, or injection—such as acknowledging their very real concern while decreasing shame, or substituting words such as “shot,” with “pinch” or “poke” to help limit fear—needle-free options for children with this phobia can eliminate the needle while delivering the medical care the child needs.²

In some cases of needle phobia, the fear is so great that it could prevent receipt of potentially life-saving care through vaccination or injection, according to the Centers for Disease Control and Prevention (CDC).²

"We know that a lot of patients are reluctant to either inject themselves or inject their children with epinephrine because of needle phobia," said Thomas Casale, MD, professor of medicine and chief of Clinical and Translational Research, Allergy and Immunology at the University of South Florida, in a previous interview with our sister publication Contemporary Pediatrics. "Having alternatives is very important.”³

Neffy to treat type 1 allergic reactions, including anaphylaxis

It has been a good year of progress for needle-free options among the pediatric population, specifically with the FDA approvals of epinephrine nasal spray (neffy; ARS Pharmaceuticals) to treat type 1 allergic reactions, including anaphylaxis, and Influenza Vaccine Live (FluMist; AstraZeneca) to prevent influenza disease for self- or caregiver-administration.

On August 9, 2024, epinephrine nasal spray was approved by the FDA for adult and pediatric patients who weigh at least 66 lbs (30 kg). The approval followed a Complete Response Letter issued nearly a year prior on September 20, 2023, because of an FDA request to complete a pharmacokinetic/pharmacodynamic study to assess repeat doses of epinephrine nasal spray compared to repeat doses of an epinephrine injector.^3,4

Once approved, epinephrine nasal spray became the first nasal spray to treat anaphylaxis, an exciting statement for those who encounter life-threatening allergic reactions and are also afraid of injection treatments.³

Epinephrine nasal spray is a single-dose nasal spray administered into 1 nostril. A second dose can be given if there is no improvement in symptoms or if symptoms worsen. The secondary dose is used with a new nasal spray to administer in the same nostril, stated the FDA when epinephrine nasal spray was approved.⁵

Russell Libby, MD, founder and president of the Virginia Pediatric Group and an assistant clinical professor of Pediatrics at the George Washington University School of Medicine and Health Sciences, stated and reinforced the benefits and importance of this FDA approval.

“I think this [treatment] will just float way to the top as soon as it becomes an option and people are aware of it, and there are a number of reasons why,” noted Libby, who also serves as a board member for the Physicians Foundation and an editorial advisory board member of Contemporary Pediatrics. “The first one, to me, is that it is needle-free and it is a stable solution. When you look at EpiPens, you have a real narrow window of temperatures where it stays stable. Sometimes it can become impotent, but more often, the potency just diminishes.”

Libby added this increased flexibility for use life and storage benefits are notable positives that can make treating with epinephrine nasal spray effective, offering peace of mind for parents. According to ARS Pharmaceuticals, epinephrine nasal spray should be stored at room temperature between 68°F to 77°F (20°C to 25°C), but storage at high temperatures up to 122°F (50°C), is “allowed for a few days,” per the nasal spray’s prescribing information.⁶

“That’s an amazing scope of stability,” said Libby. “On top of that, it lasts 30 months on the shelf without decreased potency, and when we think about shelf life and expiration dates, we think about potency, not necessarily its inability to do the intended treatment. So, it is quite an alternative; needle-free, stable in extreme temperatures, and a longer shelf life. It is amazing.”

Approval was based on comparable epinephrine blood concentration data following administration of epinephrine nasal spray or approved epinephrine injection products demonstrated in 4 studies comprising 175 healthy adults without anaphylaxis. Similar increases in blood pressure and heart rate, a pair of critical epinephrine effects when treating anaphylaxis, were demonstrated relative to injection products.³

Click here to view additional data points that led to the FDA approval of neffy including highlights of the nasal spray’s pharmacokinetic profile compared to injection, as well as additional video commentary from Thomas Casale, MD.

FluMist for self- or caregiver-administration

This updated indication of Influenza Vaccine Live, which was originally approved in 2003 for individuals aged 5 to 49 years, saw the age expand down to 2 years, as well as the ability for self- or caregiver-administration.⁷

The updated indication was approved by the FDA on September 20, 2024, and still requires a prescription. Influenza Vaccine Live contains a weakened form of live influenza virus strains sprayed in the nose. With the updated indication, the vaccine may be administered by a health care provider in a health care setting (including a pharmacy) or by the vaccine recipient or a caregiver who is 18 years of age or older, according to previous coverage by Contemporary Pediatrics.⁷

The CDC recommends everyone aged 6 months and older should receive a flu vaccine every year with rare exceptions. In seasons when flu vaccine viruses are similar to circulating flu viruses, influenza vaccination has demonstrated a risk reduction of having to visit a doctor by 40% to 60%.⁸

For infants and young children, who are among individuals with the greatest risk of flu complications, vaccination is critical. Per the CDC, flu vaccination prevents “millions of illnesses and flu-related visits to the doctor each year.”9 More specifically, in the 2019-2020 influenza season, the CDC stated that vaccination prevented approximately 7 million influenza illnesses, 3 million associated medical visits, 100,000 hospitalizations, and 7,000 associated deaths in the United States.⁸

With numbers such as these, a strong track record of effectiveness, and with your recommendations for seasonal and routine vaccines, it is clear influenza vaccination is critical in protecting the entire population, including children. For those children with needle phobia, who are likely already afraid of a doctor’s office, the at-home administration option among those aged 2 years and up is a welcomed addition and should help increase vaccination rates overall.

"This intranasal live attenuated vaccine has been around for years as an option for influenza vaccination, but utilization of the vaccine has been less than expected,” said Contemporary Pediatrics Editor-in-Chief Tina Tan, MD, professor of pediatrics at the Northwestern University Feinberg School of Medicine and the pediatric infectious diseases attending, Ann & Robert H. Lurie Children's Hospital of Chicago.⁷

"It can only be given to healthy individuals 2 to 49 years of age with no underlying conditions, including asthma. Making it available for in home use should increase the use of this vaccine and influenza vaccine, however, it will be important that the selling of this vaccine be monitored as you do not want the wrong individuals receiving the vaccine," said Tan.⁷

Tan noted that attention to detail should be taken for those administering the intranasal vaccine, but this option should help those afraid of poking and prodding.⁷

"There will need to be clear instructions as to what should be done if the person does not receive the entire dose given that this is a nasal spray, but there is some volume to it, so parts of the dose could drip out of the nose," Tan added.⁷ "In-home vaccine is not available this influenza season but is expected to be available next influenza season. It's definitely an option for needle phobic individuals."

A potential new needle-free treatment for severe allergic reactions

In an October 24, 2024, announcement from Aquestive Therapeutics, positive topline results were demonstrated in the Oral Allergy Syndrome (OAS) challenge study for epinephrine sublingual film (Anaphylm), a polymer matrix-based epinephrine prodrug product candidate.⁹

According to the announcement, the data presented from OAS marked the completion of the final supportive adult study in the development program before Aquestive meets with the FDA.⁹

In addition to seeking approval for the adult population, the company is on track to commence a pediatric study among individuals who weigh 30 kg or more in the fourth quarter of 2024. Further, Aquestive plans to submit a New Drug Application to the FDA in the first quarter of 2025.⁹

References:

1. Taking fear and pain out of needles–for your child and you. HealthyChildren.org. Updated August 3, 2022. Accessed December 6, 2024. https://www.healthychildren.org/English/safety-prevention/immunizations/Pages/managing-your-childs-pain-while-getting-a-shot.aspx
2. Healthcare providers: Understanding needle fears and phobia. Centers for Disease Control and Prevention. Updated March 17, 2022. Accessed December 6, 2024. https://www.cdc.gov/ncbddd/humandevelopment/covid-19/needle-phobia/healthcare-providers.html
3. Fitch, J. FDA approves neffy as first nasal spray to treat anaphylaxis. Contemporary Pediatrics. August 9, 2024. Accessed December 9, 2024. https://www.contemporarypediatrics.com/view/fda-approves-neffy-as-first-nasal-spray-to-treat-anaphylaxis
4. Fitch, J. FDA issues CRL for neffy nasal spray to treat allergic reactions, requests more research. Contemporary Pediatrics. September 20, 2023. Accessed December 6, 2024. https://www.contemporarypediatrics.com/view/fda-rejects-approval-of-neffy-nasal-spray-for-allergic-reactions-requests-more-research
5. FDA approves first nasal spray for treatment of anaphylaxis. FDA. Press release. August 9, 2024. December 6, 2024. https://www.fda.gov/news-events/press-announcements/fda-approves-first-nasal-spray-treatment-anaphylaxis
6. Highlights of prescribing information. ARS Pharmaceuticals. Pdf. Accessed December 6, 2024. https://www.ars-pharma.com/wp-content/uploads/pdf/Prescribing_Information.pdf
7. Fitch, J. FDA approves FluMist for self- or caregiver-administration. Contemporary Pediatrics. September 20, 2024. Accessed December 6, 2024. https://www.contemporarypediatrics.com/view/fda-approves-flumist-for-sefl--or-caregiver-administration
8. Seasonal flu vaccine basics. Centers for Disease Control and Prevention. September 17, 2024. Accessed December 6, 2024. https://www.cdc.gov/flu/vaccines/index.html
9. Aquestive Therapeutics announces positive topline results from Oral Allergy Syndrome (OAS) Challenge study for Anaphylm (epinephrine) sublingual film. Aquestive Therapeutics. Press release. October 24, 2024. Accessed December 6, 2024. https://investors.aquestive.com/news-releases/news-release-details/aquestive-therapeutics-announces-positive-topline-results-oral