Dry powder epinephrine nasal spray outcomes meet, surpass autoinjector delivery
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Key takeaways:
- Fear of needles leads to delayed deployment of autoinjector epinephrine, impacting outcomes.
- Dry powder epinephrine administered via nasal spray led to higher mean concentrations in a canine model.
A dry powder epinephrine delivered via a nasal spray yielded drug exposures that were equal to or higher than those achieved through autoinjector in a canine model, according to the results of a study performed by Belhaven Biopharma.
“Alternatives to epinephrine intramuscular injections are needed for many reasons,” Scott Lyman, MS, MBA, CEO and cofounder of Belhaven Biopharma, told Healio. “The most obvious is widespread needle phobia, which results in dose hesitancy, leading to poor outcomes.”
Lyman also said autoinjectors are too big for some patients to carry all the time and that accurate administration requires training. Plus, he said, they include liquid epinephrine, which is susceptible to heat degradation, resulting in short shelf life.
“Most intramuscular injections reach maximum epinephrine levels in 20 minutes or more,” he added. “Our dry powder nasal device delivers maximum epinephrine levels in about 5 minutes. This is key for an emergency-use product like epinephrine.”
Conducted in collaboration with Lovelace Biomedical, the crossover study involved four female beagles. Each dog received 60 mg intranasal doses of Belhaven’s 10% BBP01 (Nasdepi) intranasal epinephrine (or 6 mg of epinephrine), 30 mg of Belhaven’s 20% BBP01 intranasal epinephrine (or 6 mg of epinephrine), and a 0.3 mg dose of epinephrine delivered via an EpiPen (Mylan/Viatris) autoinjector, with a washout period of 2 days between doses.
Researchers collected blood samples before dosing and at 10 and 20 minutes after anesthesia. Samples also were collected at 2 or 3, 5, 7, 10, 15, 20, 30, 60, 90 and 120 minutes after dosing.
“The significant result of this canine study was the speed in which maximum epinephrine concentrations were achieved and the efficiency in which the absorption occurred via the nasal route of administration,” Lyman said.
Group mean concentrations of epinephrine were significantly higher with intranasal administration compared with autoinjector. The intranasal groups had partial areas under the curve (AUCs) that were two to four times higher than the autoinjector groups, mostly due to the higher exposures in the first 30 minutes after the dose, the researchers said.
Specific AUCs for the autoinjector group (n = 4) included 7,388 min*pg/mL (67.4%) at 10 minutes, 22,480 min*pg/mL (34.5%) at 30 minutes and 54,490 min*pg/mL (41.7%) at 60 minutes.
AUCs after the 60 mg doses of 10% BBP01 (n = 3) included 30,830 min*pg/mL (54.4%), 74,270 min*pg/mL (66.5%) and 115,500 min*pg/mL (52.4%). In the group of 30 mg doses of 20% BBP01 (n = 4), AUCs included 43,750 min*pg/mL (14.3%), 90,590 min*pg/mL (22%) and 133,500 min*pg/mL (20.2%).
The intranasal administration also led to higher and faster peak epinephrine concentrations than autoinjector administration. Specifically, autoinjector administration had a mean maximum concentration (Cmax) of 1,706 pg/mL (44.9%) and a mean time to maximum concentration (Tmax) of 61 minutes (78.6%).
The 60 mg doses of 10% BBP01 had a mean Cmax of 4,170 pg/mL (48.7%) and a mean Tmax of 3.7 minutes (31.5%). The 30 mg doses of 20% BBP01 had a mean Cmax of 6,675 pg/mL (37.1%) and a mean Tmax of 4 minutes (35.4%).
In fact, the researchers noted that all the dogs had a Tmax of 5 minutes or less with intranasal administration, but only one dog had a Tmax of 5 minutes of less with autoinjector administration.
Overall, the researchers said that epinephrine treatments need to be accessible and efficacious, with straightforward administration, and that BBP01 meets these criteria.
BBP01’s dry powder provides a stable formulation that can be easily transported, the researchers said. And unlike autoinjectors, BBP01 only requires users to place the nozzle into the nose and depress the actuator, the researchers continued.
“This study confirmed our hypothesis that dry powder nasal epinephrine was the ideal way to deliver this key medicine during a severe allergy event,” Lyman said.
This study indicates the drug’s efficacy as well, the researchers concluded, with exposures that not only were equivalent to those provided by autoinjectors but also faster with longer sustainability, which may inhibit the anaphylactic cascade and help with breakthrough events.
“Results from this canine study led to our first clinical trial, which was completed in December 2023. The results from this pilot human study will be presented at a future scientific meeting at the end of the year,” Lyman said. “We are planning to run a dose confirmation study by the end of the year to help choose the bioequivalent dose for our pivotal bioequivalency study vs. the EpiPen.”