Epinephrine nasal spray outcomes comparable with injections among pediatric patients
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Key takeaways:
- Fears associated with needles may cause patients and caregivers to delay their use of epinephrine autoinjectors.
- Most adverse events associated with nasal spray were mild, and none were serious.
WASHINGTON — An epinephrine nasal spray resulted in outcomes that were comparable with injections in pediatric patients, according to a poster presented at the American Academy of Allergy, Asthma & Immunology Annual Meeting.
These findings indicate the spray’s potential as an effective alternative for treating severe allergic reactions in children, Sarina Tanimoto, MD, MBA, chief medical officer, ARS Pharma, and colleagues wrote.
Challenges and fears
Noting challenges and fears associated with epinephrine autoinjectors, the researchers said ARS Pharma’s neffy epinephrine nasal spray is designed to provide needle-free treatment of type I allergic reactions including anaphylaxis.
“The literature indicates that parents are fearful and anxious to inject their own children with an epinephrine autoinjector, which causes them to hesitate and potentially allow an allergic reaction to progress to a more serious and potentially life-threatening event,” Tanimoto told Healio.
Parents also worry that caretakers, guardians or teachers may not be willing or know how to use autoinjectors, given their complexity and risk for injury due to the needle, she continued.
“There are more than 3,500 accidental self-injections in the U.S. annually with epinephrine autoinjectors, according to National Poison Center data,” Tanimoto said.
Additionally, she continued, pediatric patients are especially afraid of being injected or self-injecting. Pediatric patients routinely resist injection as well, she added, with twisting and jerking that can lead to lacerations and injuries due to the needle.
Tanimoto further noted the large and bulky design of autoinjectors, which makes it less likely for children to carry them, as well as the social stigma that goes along with carrying them, particularly among adolescents.
As an alternative to injection, Tanimoto said that neffy addresses these concerns among pediatric patients by removing the fear and anxiety associated with the needle, since neither children nor adults can harm themselves or the child with it.
Also, Tanimoto said, neffy is much smaller than autoinjectors and can fit in a pocket or in a carrying case, so it is easy to carry. It is easy to use as well, she continued, with 100% of children able to use it with training and 100% of adults able to use it without training.
Study design, results
The randomized, single-dose, phase 1 study comprised 42 children with histories of significant, systemic allergies to food, insects, venom or drugs that required prescriptions for epinephrine products.
The 21 children (age range, 4-11 years; 13 boys; mean weight, 25 kg) who weighed between 15 kg and 30 kg received a 1 mg dose of neffy, and the 21 children (age range, 8-17 years; 12 boys; mean weight, 54 kg) who weighed 30 kg or more received a 2 mg dose.
Mean maximum epinephrine concentrations (Cmax) included 651 pg/mL in the 15 kg to 30 kg group and 690 pg/mL in the 30 kg or more group. Median times to reach Cmax (Tmax) included 20 minutes for the 15 kg to 30 kg group and 29.5 minutes for the 30 kg or more group.
Additionally, mean total exposure values included 35,100 min*pg/mL (mean percentage coefficient of variation, 57.3%) for the 15 kg to 30 kg group and 40,200 min*pg/mL (mean percentage coefficient of variation, 92.8%) for the 30 kg or more group.
Mean maximum effects (Emax) on systolic blood pressure included 13.4 mmHg for the 15 kg to 30 kg group and 12.2 mmHg for the 30 kg or more group. Also, median time to reach Emax (TEmax) included 20 minutes for the 15 kg to 30 kg group and 25 minutes for the 30 kg or more group.
In diastolic blood pressure, mean Emax included 7 mmHG for the 15 kg to 30 kg group and 8.67 mmHg for the 30 kg or more group. Median TEmax included 15 minutes for the 15 kg to 30 kg group and 25 minutes for the 30 kg or more group.
Mean Emax for pulse rate included 18.5 bpm for the 15 kg to 30 kg group and 16.39 bpm for the 30 kg or more group, with median TEmax results including 25 minutes for the 15 kg to 30 kg group and 44 minutes for the 30 kg or more group.
Overall, the researchers said that these pharmacokinetic and pharmacodynamic profiles were within the ranges of those achieved with approved injection products.
The researchers also characterized most of the adverse events that occurred as mild, adding that none of them were serious, nor did any of them result in participants dropping out of the study. Its use was considered safe and well tolerated, Tanimoto said.
“The most common treatment-related adverse events were mild to moderate nasal discomfort or mild nasal congestion (11.9%),” she said. “This is consistent with the neffy safety data in adults, where the most common treatment-related adverse event was mild nasal discomfort (9.7%).”
Only two (4.8%) of the children in this study experienced moderate adverse events, including nasal discomfort and sneezing, or nasal discomfort, post-nasal drip and throat irritation, Tanimoto said.
Conclusions, next steps
These findings indicate that neffy can achieve pharmacokinetic exposures in a range comparable to or slightly greater than approved injection products, Tanimoto said.
“The pharmacodynamic responses on surrogate markers of efficacy in pediatric patients such as change in systolic blood pressure show that the receptors involved in reversing anaphylaxis symptoms are fully activated,” she said. “Therefore, neffy should be efficacious.”
In another study presented at the AAAAI Annual Meeting, 100% of pediatric patients with anaphylaxis induced by oral food challenges responded to a single dose of neffy, indicating that the pharmacokinetic profile described in this poster translates into real-world efficacy, Tanimoto continued.
“We have also shown in formal human factors studies that 100% of children can successfully dose neffy after training, whereas the literature reports that many pediatric patients do not correctly use their EpiPen [Mylan/Viatris] and other autoinjector devices,” she added.
Based on these findings, the researchers said they expected neffy to be a safe and effective treatment option for children who are experiencing anaphylaxis and other severe allergic reactions.
ARS Pharma is now seeking approval for 2 mg doses of neffy to treat type I allergic reactions in children who weigh 30 kg or more. The company expects to resubmit its new drug application to the FDA in the middle of the first half of 2024, with FDA approval 6 months later.
After that, Tanimoto said, the company will request FDA approval for 1 mg doses to treat children who weigh 15 kg to 30 kg in a supplemental new drug application, with approval expected in early 2025.
“We also plan to develop a lower dose for children less than 15 kg in weight as part of a commitment to the European regulatory authorities,” Tanimoto said.