Nasal Powder Epinephrine Formulation Comparable to EpiPens for Anaphylaxis

New nasal powder formulations of epinephrine may allow for greater stability and plasma exposure for patients with anaphylaxis similar to epinephrine auto-injectors (EpiPens), according to recent findings.¹

This new research was presented at the 2024 American Academy of Allergy, Asthma & Immunology (AAAAI) Annual Meeting in Washington, DC, and may lead to an expansion of the currently limited options for patients with severe allergic reactions who seek a needle-free option for treatment.

“After more than 100 years of clinical use, a needle-free option for epinephrine finally seems to be within reach, thanks to new delivery technologies combined with efforts from regulatory agencies to find a scientifically sound development path,” lead author, Martin Jönsson, MSc Pharm, said in a statement. “The nasal amorphous powder technology we have developed provides both effective absorption and excellent stability that may benefit patients, ensuring that the drug is not degraded when carried and is still effective when needed”

Jönsson and colleagues used a cross-over study involving an assessment of 40 healthy participants who had volunteered for the study, comparing the bioavailability and hemodynamic response of a 0.3 mg EpiPen compared to four 1 mg formulations of nasal powder treatments. These proprietary powder formulations had been created via spray-drying and were subjected to accelerated stability testing and comparisons to epinephrine auto-injectors.

Overall, the investigators reported that stability had continued, even under accelerated conditions, with the preservative-free powder formulations. These formulations were shown to have less than 1% total degradation over the course of a year versus the 32% degradation rate of epinephrine auto-injectors.

The research team noted the swift absorption observed in their epinephrine powder formulations. They added that plasma levels which were comparable to auto-injectors had been observed within 5-10 minutes of use among the participants assessed in the study.

In their comparisons to auto-injectors, the investigators also found that peak and early baseline adjusted levels of exposure among those given the powder formulations also had comparable results to those of the auto-injectors, with a range from about 83% - 120%. They also noted that total exposure had been 30% - 60% higher for those treated with nasal powders.

Another aspect shown to have similar results to those of auto-injectors were hemodynamic effects, such as heart rate and blood pressure. The team did add, however, that there was slightly elevated blood pressure among powder users.

Jönsson and colleagues concluded with the notion that the nasal powder formulations of epinephrine had shown superior stabilities and had comparable plasma exposure to epinephrine auto-injectors. This may, they added, allow for an alternative treatment option for those experiencing anaphylaxis.

Should such a treatment option become available, it could face competition with such competitors as the intranasal epinephrine treatment known as ‘neffy,’ widely-anticipated in 2023 as the first non-injection alternative to EpiPens.²

Neffy faced a major hurdle in the form of a Complete Response Letter (CRL) from the US Food and Drug Administration (FDA), and the response by the FDA proved to be surprising for some in the field of allergy and immunology. The new nasal powder formulations evaluated by Jönsson and his team may end up becoming the next possible alternative should they be approved by the FDA in the near future.

The investigators assessing the powder formulations noted that the current needle-based autoinjectors used for Type 1 allergic reaction treatment have shortcomings that could potentially be addressed by powder formulations.¹

References

1. ^{Study Shows Nasal Powder Epinephrine Provides Superior Stability to EpiPens. American Academy of Allergy, Asthma & Immunology. February 5, 2024. https://www.aaaai.org/about/news/news/2024/epinephrine. Date accessed: February 23, 2024.}
2. ^{Smith T. Edwin H. Kim, MD: Responding to FDA Decision Not to Approve ‘Neffy’ Treatment. HCPLive. September 26, 2023. https://www.hcplive.com/view/edwin-h-kim-md-responding-to-fda-decision-not-to-approve-neffy-treatment. Date accessed: February 26, 2024.}