Dry powder epinephrine nasal spray outcomes comparable with intramuscular injection
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Key takeaways:
- Subjects had two doses each of Belhaven Biopharma’s BBP01 and intramuscular epinephrine.
- Subjects had faster and greater increases in heart rate and blood pressure with BBP01.
BOSTON — An intranasal epinephrine powder produced responses that were comparable with intramuscular administration, according to a poster presented at the American College of Allergy, Asthma & Immunology Annual Scientific Meeting.
All the treatment-emergent adverse events were mild or moderate as well, Scott Lyman, MS, MBA, CEO and cofounder of Belhaven Biopharma, which produces the BBP01 (Nasdepi) dry powder spray, and colleagues wrote.
There are several reasons why patients would prefer alternatives to autoinjectors for epinephrine delivery, Lyman told Healio.
“The reasons we hear about the most are the high cost,” he said, adding that “it’s a relatively large device to carry.”
Patients also are afraid of needles, Lyman continued.
“Autoinjectors go bad in the heat and have a relatively short shelf life,” he further noted, adding that they also have complications in correct administration and are unable to be recycled.
The phase 1, open-label, single-sequence, treatment-crossover, dose-finding study enrolled 12 subjects (mean age, 41.4 years; males, n = 9; white, n = 12). The mean weight of the subjects was 78.5 kg, and the mean BMI was 26.23 kg/m2.
Each subject received a 3.5 mg dose of BBP01, a 0.3 mg dose of epinephrine delivered via intramuscular (IM) injection, a 0.5 mg IM epinephrine dose, and a 5.5 mg dose of BBP01, in that order, with a washout period of 72 hours or more between each dose.
Before and periodically after each dose, physicians conducted nasal, vital sign and physical examinations of each subject, who returned for a safety follow-up visit between 3 and 5 days following the last dose. Subjects completed a questionnaire about nasal irritation as well.
Nine of the subjects finished the study. One discontinued participation due to an adverse event after receiving the 3.5 mg dose of BBP01. Two subjects withdrew voluntarily.
All the subjects experienced at least one mild or moderate treatment-emergent adverse event and at least one treatment-emergent adverse event related to a drug. None of the treatment-emergent adverse events were severe or life-threatening. Also, there were no deaths or other serious adverse events.
The most common treatment-emergent adverse events included nasal discomfort (66.7%), headache (50%), increased lacrimation (41.7%), epistaxis (33.3%) and palpitations (33.3%). All the treatment-emergent adverse events resolved before the study was over.
Specifically, treatment-emergent adverse events were experienced by 11 of 12 subjects after the 3.5 mg dose of BBP01, one of nine subjects after the 0.3 mg IM dose, seven of 11 subjects after the 0.5 mg IM dose and seven of nine subjects after the 5.5 mm dose of BBP01.
“The speed of epinephrine absorption into the systemic bloodstream was very fast, and the drug levels were sustained for the first 60 minutes after dosing,” Lyman said.
Median maximum concentrations of plasma epinephrine included 323 pg/mL with the 3.5 mg dose of BBP01, 413 pg/mL with the 5.5 mg dose, 167 pg/mL with the 0.3 mg IM dose and 360 pg/mL with the 0.5 mg IM dose. The researchers called these increases dose dependent.
Similarly, median times to maximum concentration included 28 minutes with the 3.5 mg BBP01 dose, 18 minutes with the 5.5 mg BBP01 dose, and 48 minutes for both the 0.3 mg and 0.5 mg IM doses. Compared with the IM doses, BBP01 achieved a faster 100 pg/mL increase as well.
Median areas under the curve through 360 minutes after dosing included 22,400 min*pg/mL for the 3.5 mg BBP01 dose, 48,050 min*pg/mL for the 5.5 BBP01 dose, 18,200 min*pg/mL for the 0.3 mg IM dose and 34,300 min*pg/mL for the 0.5 mg IM dose.
Compared with the 0.3 mg IM dose, which the researchers called the FDA-approved dose, the relative bioavailability based on maximum concentration for BBP01 was 13.5% higher with the 3.5 mg dose and 21.3% higher with the 5.5 mg dose.
Based on the area under the curve through 360 minutes, relative bioavailability was 11.9% better with the 3.5 mg dose of BBP01 and 18.8% with the 5.5 mg dose compared with the 0.3 mg IM dose.
The researchers further said that heart rate, systolic blood pressure and mean arterial pressure increased after all the doses, which had minimal effects on diastolic blood pressure as well. Also, the researchers noted that the increases in heart rate and blood pressure were faster and greater with BBP01.
Lyman also cited the powder’s robust stability and resistance to extreme environmental conditions. Findings pertaining to this stability will be presented at the Drug Delivery to the Lungs 2024 conference in Edinburgh, Scotland, in December.
Based on these findings, the researchers said that BBP01 has potential as an effective, noninvasive and alternative delivery method for epinephrine that achieves fast and systemic absorption.
Next, the researchers said their work will continue with an open-label, single-sequence pharmacokinetics study comparing BBP01 with epinephrine autoinjectors among subjects who have and who do not have induced rhinitis.
“We plan to complete another clinical trial by the end of the year to confirm the commercial dose and test Nasdepi after inducing rhinitis (runny nose) in healthy volunteers,” Lyman said. “Rhinitis is a common result of a severe allergy reaction, and we want to ensure we deliver an equivalent dose in those patients.”