Q&A: Nasal spray effectively fills need for needleless epinephrine delivery

Key takeaways:

• Fears about using needles cause many patients to delay autoinjector use.
• The neffy nasal spray eliminates those fears without compromise in performance.
• The FDA has requested additional research.

The neffy epinephrine nasal spray from ARS Pharma produced pharmacokinetic and pharmacodynamic responses that were comparable with injected delivery, according to a study published in The Journal of Allergy and Clinical Immunology.

An FDA committee recommended approving the spray for treating anaphylaxis and other type I allergic reactions in May but, last month, the FDA asked ARS Pharma to conduct an additional study involving repeat doses under allergen-induced allergic rhinitis conditions. The FDA also has scheduled a Type A meeting to discuss its review further.

Healio spoke with Thomas B. Casale, MD, lead author of the study and chief of clinical and translational research in the division of allergy and immunology at University of South Florida Morsani College of Medicine, to find out more.

Healio: What are the drawbacks of using autoinjectors for treating anaphylaxis?

Casale: For decades, the only way to administer epinephrine has been through needle-based products — an often painful and anxiety-inducing needle injection of epinephrine, which, in some cases, results in delay or failure to administer the lifesaving treatment at the onset of symptoms and therefore increases the risk for a severe reaction or negative outcomes requiring additional emergency medical treatment.

Reducing time to administration is key to achieving better clinical outcomes and improvements in quality of life for patients and their caregivers, and we know that for many, the needle is a barrier that causes dangerous hesitation.

Also, autoinjector devices carry risks for accidental injury to both the patient and caregiver, have the potential to inject into a blood vessel, are heat-sensitive and inconvenient to carry, and can be difficult or anxiety-provoking to use.

An estimated 45% of patients with severe allergy do not fill their epinephrine prescriptions, and among the 3.3 million people who do obtain an injection device, more than 50% do not carry their autoinjector devices with them and up to 83% of patients/caregivers fail to administer or delay using epinephrine autoinjectors even when they know a severe allergic reaction is occurring.

Healio: How does neffy improve upon these drawbacks?

Casale: Epinephrine treatment is only effective if available, readily usable and administered appropriately. As previously stated, it is well known that a number of patients and caregivers either do not acquire an epinephrine product, do not carry it with them, refuse to use it when necessary, or hesitate to administer it due to needle-related fears.

Regrettably, stalling or failing to promptly administer treatment when symptoms appear greatly increases the chance of hospitalization and has been associated with fatalities. This underscores the importance of eliminating the obstacle posed by needle injections.

Providing patients and caregivers with a needle-free option such as neffy allows for improved preparedness and response to give epinephrine quickly, confidently and without hesitation that is caused by fear of needles.

The neffy epinephrine nasal spray is a drug product being developed to deliver systemic epinephrine levels in the range of approved injection products through a proven nasal spray device using a needle-free, absorption-enhancing technology without pain or irritation to patients.

In fact, neffy utilizes the same device as Narcan (naloxone hydrochloride, Emergent BioSolutions) nasal spray, an FDA-approved nasal delivery system that has been saving lives in cases of opioid overdoses for more than 5 years, and Imitrex (sumatriptan, GSK) nasal spray, which has been approved to treat migraines for more than 20 years.

Healio: Were there any particularly significant or surprising results in this study you would like to spotlight?

Casale: There were several important results in this study indicating that neffy, if approved, could be a safe and effective option for first-line treatment for severe allergic reactions. Key study results demonstrate neffy’s pharmacokinetic profile was bracketed by approved injection products, with pharmacodynamic responses that were comparable with or better than approved injection products.

Also, neffy resulted in robust responses on pharmacodynamic (PD) surrogates of efficacy observed even at 1 minute after dosing that were comparable with, or greater in magnitude than, EpiPen (Viatris/Myan Specialty). Seeing systolic blood pressure and heart rate increases almost immediately with neffy are highly reassuring, as these signs indicate activation of adrenergic receptors that reverse the anaphylaxis symptoms.

Repeat doses of neffy resulted in statistically greater mean maximum responses on PD surrogates for efficacy compared with EpiPen, which could be clinically important in severe cases of anaphylaxis that often need a repeat dose of epinephrine, where patients may experience hypotensive crisis.

With repeat doses of 2 mg of neffy, a pharmacokinetic profile greater than EpiPen is warranted given the more serious nature of the disease, including hypotension. Also, 2 mg of neffy is dose proportional with repeat dosing and between doses, whereas injection products have been proven not to be dose proportional. This results in a more consistent and numerically better epinephrine exposure as well as statistically better PD response with neffy 2 mg vs. twice dosing of EpiPen.

Healio: What makes these results surprising or significant?

Casale: These results show that neffy treatment is comparable with currently approved epinephrine injection products in terms of increasing systolic blood pressure and heart rate within minutes to reverse the anaphylaxis symptoms, which is highly reassuring from a clinical perspective.

When a severe life-threatening allergic reaction occurs, it is necessary to administer epinephrine as soon as possible. With its needle-free intranasal administration, neffy may provide a safe and effective epinephrine delivery option, particularly for patients who delay or avoid dosing due to needle-phobia, which may save lives from anaphylactic shock.

These results are particularly important for patients and caregivers who are reluctant to carry and use injection devices. Epinephrine is a lifesaving medication but, for decades, the only way to administer it has been through needle-based products. These devices carry risks for accidental injury to both the patient and caregiver, have the potential to inject into a blood vessel, are heat-sensitive and inconvenient to carry, and can be difficult to use. Auto-injectors can be anxiety-provoking for people with life-threatening allergies, as well as their caregivers, such as parents or teachers.

For all these reasons, many patients and caregivers do not obtain an epinephrine product at all, do not carry it, refuse to use it when needed, or hesitate to administer epinephrine due to the fear of needles.

Yet we know that delay or failure to administer the lifesaving treatment at the onset of symptoms increases the risk for a severe reaction or negative outcomes, which is why providing patients and their caregivers with a needle-free option such as neffy could increase the likelihood that a patient or their caregiver will administer epinephrine as soon as symptoms arise.

Healio: What is the next step in this research?

Casale: The FDA recently requested ARS Pharma to conduct one more study with twice dosing in patients having an allergic rhinitis episode following a nasal-allergen challenge. ARS Pharma already performed this study with a single dose of neffy and, in fact, showed more rapid absorption compared with normal conditions. ARS Pharma will conduct this additional study and anticipates a resubmission to the FDA in the first half of 2024.

References:

• ARS Pharmaceuticals announces scheduling of a Type A meeting with the US FDA for neffy (epinephrine nasal spray). https://ir.ars-pharma.com/news-releases/news-release-details/ars-pharmaceuticals-announces-scheduling-type-meeting-us-fda. Posted Oct. 6, 2023. Accessed Oct. 18, 2023.
• Casale TB, et al. J Allergy Clin Immunol. 2023;doi:10.1016/j.jaci.2023.08.007.

For more information:

Thomas B. Casale, MD, can be reached at tbcasale@usf.edu.