Needle-free epinephrine an alternative for anaphylaxis?

In a study presented at AAAAI 2024, epinephrine in preservative-free, nasal powder formulations demonstrated superior stability and comparable plasma exposure to the EpiPen^® autoinjector, thus providing a less-invasive treatment option for severe allergic reactions including anaphylaxis.

“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,” shared lead study author Martin Jönsson from Orexo AB, Uppsala, Sweden, in a press release. [https://www.aaaai.org/about/news/news/2024/epinephrine]

“The nasal amorphous powder technology that 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 continued.

Forty healthy individuals participated in this five-period, crossover study that assessed the bioavailability and haemodynamic response of four 1-mg powder formulations and compared it with an approved autoinjector that contained 0.3-mg doses of epinephrine. Proprietary amorphous powder formulations were developed using spray-drying and their stability was assessed under accelerated conditions (40°C, 75-percent relative humidity). [AAAAI 2024, abstract L22]

The nasal powder formulation demonstrated stability under accelerated conditions, showing ≤0.65-percent degradation for over 12 months. With the autoinjector, the corresponding degradation rate was 31.5 percent within the same timeframe.

The epinephrine from the nasal powder was also rapidly absorbed, with plasma levels comparable to the levels observed via autoinjector delivery within approximately 5–10 minutes.

Peak and early exposure were also comparable between the nasal powder formulation and the autoinjector (C_max and AUC_0-20min estimated to 83–120 percent of the autoinjector for the different formulations). Total exposure was about 30–60 percent higher with the powder form.

“The onset of haemodynamic effects (blood pressure [BP] and heart rate) were comparable [between the nasal powder and the] autoinjector, with a somewhat higher increase in BP,” noted Jönsson. With epinephrine powder, the mean peak increase in BP was 18–21/11–14 mm Hg. With the autoinjector, the corresponding increase was 11/6 mm Hg.

Addresses the limits of autoinjectors

Treatment options for anaphylaxis are currently limited to parenteral autoinjectors, with limitations such as intimidating needle-based administration that may deter timely use, and poor stability requiring storage conditions that are incompatible with many activities, Jönsson noted. Patients may also consider the bulkiness of autoinjectors as an inconvenience.

“Many patients fear the needle,” Jönsson noted in a separate report. Moreover, patients may not bring autoinjectors with them regularly even if they are aware of the need in the event of an allergy attack. And even if they do, they may only find it handy when the reaction has gone severe, he pointed out.

Given the superiority of nasal powder formulations to the autoinjector in terms of stability, as well as their comparability in terms of plasma exposure, the results of this study underpin the ability of nasal epinephrine powder to address the limits of autoinjectors.

Although the powder formulations are still under development, once approved, these may provide a needle-free, convenient, more stable, and fast-acting alternative for the management of anaphylaxis.