Neffy pharmacokinetic profiles compared to epinephrine injections

Sarina Tanimoto, MD, MBA, chief medical officer, ARS Pharma | Image Credit: ARS Pharma

Neffy (epinephrine nasal spray; ARS Pharma) is a potential needle-free option to treat type 1 allergic reactions, including anaphylaxis in adults and children weighing more than 66 lbs.¹

ARS Pharmaceuticals recently announced topline data for repeat doses of neffy, compared to repeat doses of epinephrine intramuscular (IM) injections with and without nasal allergen challenge (NAC) conditions in response to the FDA's request of a pharmacokinetic (PK) and pharmacodynamic (PD) study issued in a September 2023 Complete Response Letter (CRL).¹

Sarina Tanimoto, MD, MBA, chief medical officer, ARS Pharma, explains data from the study "Pediatric doses of neffy (intranasal nasal spray) demonstrate pharmacokinetic profiles that are equivalent to epinephrine injections products," in the Q+A interview below.

Data will be presented at the 2024 American Academy of Allergy, Asthma, & Immunology Annual Meeting (AAAAI) in Washington DC from February 23 to February 26, 2024.

Contemporary Pediatrics:

Can you explain how this study was organized, and what methods were used to compare pharmacokinetic profiles between neffy and epinephrine injection products?

Sarina Tanimoto, MD, MBA:

This study was organized as a single-arm, open-label [Pharmacokinetic-Pharmacodynamic] (PK/PD) study dosing neffy 0.65 mg, 1 mg or 2 mg (depending on subject weight) with PK/PD modeling to bridge to the data collected with injection in adults. A total of 80 total [individuals] were enrolled during the pediatric development of neffy. The 42 [individuals] presented in this AAAAI 2024 poster represents the data for the 2 doses (1 mg and 2 mg) dosed in the intended population for approval – 1 mg for 15-30 kg [individuals], and 2 mg for 30 kg + [individuals].

[The] age of [participants] ranged from 4 years to 17 years old. Blood samples were collected over 120 minutes to determine how much epinephrine was absorbed after administration of neffy and PD measures included blood pressure and heart rate which are directly impacted by epinephrine exposure.

The reason for the single-arm, open-label design was that FDA agreed it was not practical to conduct a randomized, crossover PK/PD study in children that included injection as a comparator due to a variety of factors including the intense study conduct with respect to blood draws and duration, and general difficulty enrolling children wiling to be injected with epinephrine. FDA requested 10 [individuals] per dose group, but Europe requested 20 [individuals] per dose group, which is why this study has 21 [individuals] per dose group (for each 1 mg and 2 mg).

Separately from this EPI-10 study, to compare these data to injection, integrated PK analyses, including pharmacological base absorption model (PBAM) and a population pharmacokinetics assessments (POP PK) model were also used to extrapolate results from 0.3 mg IM injection and 0.3 mg EpiPen in our adult studies to pediatric subjects. These analyses demonstrated that neffy achieved exposures in pediatrics that are comparable to or slightly greater than that observed with injection in adults.

Contemporary Pediatrics:

Can you explain the make-up of the study?

Tanimoto:

EPI 10 included a total of 80 doses of neffy. Twelve [individuals] with body weight 15-30 kg received 0.65 mg neffy and 21 [individuals] with body weight 15-30 kg received 1 mg neffy. In the higher weight group of 30 kg or greater, 26 subjects received a 1 mg dose of neffy and 21 subjects received a 2 mg dose of neffy.

The data presented in this poster from the study included a total of 42 pediatric [individuals] that received the commercial doses of neffy which will be 1 mg for children 15 to <30 kg and 2 mg for children 30 kg or greater.

Half the [individuals] (n = 21) were 15-30 kg in weight, while the other half (n = 21) were 30kg+ in weight. Age range of subjects in the study is 4 to 17 years.

Contemporary Pediatrics:

Can you highlight the benefits of neffy compared to epinephrine injections, of course acknowledging there is no needle. What other benefits are there for neffy regarding the pediatric indication?

Tanimoto:

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.

Parents also worry whether caretakers, guardians or teachers will be willing or know how to use the autoinjector device when the parent is not present given their complexity and risk of injury due to the needle. There are more than 3,500 accidental self-injections in the [United States] annually with epinephrine autoinjectors according to National Poison Center data.

Furthermore, pediatric patients are particularly fearful of being injected or self-injecting. There are very routine reports of pediatric patients resisting injection, and twisting and jerking, which led to lacerations and injuries due to the needle.

Neffy, as an alternative to injection, addresses all these concerns in pediatric patients by removing the fear and anxiety associated with the needle as neither children nor untrained adults can harm the child or themselves with neffy.

Autoinjectors are also large and bulky, which makes it less likely for children to carry the device; there is some social stigma that has been reported with carrying the device around, especially among adolescents. Literature indicates that only 45% of pediatric subjects carry one epinephrine autoinjector with them, and only 22% of pediatric subjects carry 2 devices, as recommended by treatment guidelines.²

Neffy is easy for children to carry as it is much smaller than autoinjectors, fitting in a pocket in a convenient carrying case that can fit 2 devices as guidelines recommend (since a second dose is required in ~10% of events) just like a wireless earbuds case.

Many pediatric patients and their caregivers do not correctly use their EpiPen and other autoinjector devices. In one published study, only 32% of pediatric subjects correctly demonstrated use of the epinephrine autoinjector.³ In another randomized controlled study, only 43% of mothers were able to use an epinephrine autoinjector after training.⁴

Neffy is also easier to use than an autoinjector as 100% of children were able to use neffy in formal human factors studies after training, and even 100% of adult lay people (e.g. third-party caregivers) who have no knowledge of anaphylaxis were able to use neffy without any training. Therefore, both children and their caregivers may more easily be able to use neffy confidently at the first sign of an allergic reaction without anxiety of fear, or risk of injury from the needle.

References:

1. Fitch, J. Neffy epinephrine nasal spray demonstrates positive data in repeat dosing study. Contemporary Pediatrics. February 21, 2024. Accessed February 23, 2024. https://www.contemporarypediatrics.com/view/neffy-epinephrine-nasal-spray-demonstrates-positive-data-repeat-dosing-study

2. Warren CM, Zaslavsky JM, Kan K, Spergel JM, Gupta RS. Epinephrine auto-injector carriage and use practices among US children, adolescents, and adults. Ann Allergy Asthma Immunol. 2018;121(4):479-489.e2. doi:10.1016/j.anai.2018.06.010

3. Sicherer SH, Forman JA, Noone SA. Use assessment of self-administered epinephrine among food-allergic children and pediatricians. Pediatrics. 2000;105(2):359-362. doi:10.1542/peds.105.2.359

4.Umasunthar T, Procktor A, Hodes M, Smith JG, Gore C, Cox HE, Marrs T,  Hanna H, Phillips K , Pinto C, Turner PJ, Warner JO, Boyle RJ. Patients' ability to treat anaphylaxis using adrenaline autoinjectors: a randomized controlled trial. Allergy 2015; 70: 855–863.