Intranasal epinephrine spray outcomes comparable with autoinjectors

SAN ANTONIO — An epinephrine nasal spray achieved pharmacokinetic and pharmacodynamic outcomes comparable with manual administration, according to data presented at the American Academy of Allergy, Asthma & Immunology Annual Meeting.

The 13.2 mg intranasal epinephrine spray (Utuly, Bryn Pharma) also appeared safe and well-tolerated, results showed.

Patient needs

The patient community has been vocal about the need for needle-free and convenient alternatives to intramuscular autoinjectors, which are the standard of care for anaphylaxis in outpatient settings, David Dworaczyk, PhD, CEO of Bryn Pharma, told Healio.

“Fear and anxiety surrounding needles lead to a lack of compliance for people with severe allergies at surprisingly high rates. This is compounded by user error due to lack of training and injection site injuries,” Dworaczyk said.

Even when people have autoinjectors and there is a clear and present need to use them, he continued, many people hesitate because of the drama of the anaphylactic event and the act of injection.

“It makes a frightening event even worse,” Dworaczyk said.

People who should carry epinephrine all the time often do not because of the inconvenient and bulky form factors that many autoinjectors have, Dworaczyk said.

“There’s been no innovation in this space since autoinjectors came on the market in 1987. It’s not an understatement to say that this population has been neglected until recently. This glaring unmet need gets to the heart of why innovation in this space is so necessary,” he said.

When people do not carry or use their autoinjectors appropriately, Dworaczyk explained, their symptoms can become more severe and lead to a need for a second dose of epinephrine. Rates of hospitalizations and critical outcomes also may increase, he added.

“Bringing a safe, effective, quick-onset, innovative, needle-free, easy-to-carry and easy-to-use device to the market is central to our mission,” Dworaczyk said.

Study design, results

Dworaczyk and Allen Hunt, MD, a research physician at Celerion, included 100 healthy volunteers in their open-label, three-period crossover study. Participants received a single 13.2 mg intranasal dose of epinephrine comprising two consecutive 6.6 mg sprays via opposite-nostril (n = 50; cohort 1) or single-nostril (n = 50; cohort 2) dosing.

All participants then received 0.3 mg intramuscular doses of epinephrine via autoinjector and 0.5 mg doses of epinephrine with a manual syringe, the order of which was determined in a randomized fashion, with a span of at least 24 hours between each dosing method.

Researchers assessed the proportion of participants achieving unadjusted and baseline-adjusted epinephrine concentrations of 50 pg/mL, 100 pg/mL and 200 pg/mL at 10, 20, 30 and 60 minutes after each dose, finding that the nasal spray showed as good or better results as the 0.3 mg intramuscular dose.

Maximum concentrations of epinephrine included 429.4 pg/mL with the nasal spray and 328.6 pg/mL with the autoinjector. Also, the nasal spray achieved 39,060 g*min/mL of systemic exposure over 6 hours, whereas the autoinjector achieved 17,440 g*min/mL.

The differences in maximum concentrations and systemic exposure between the nasal spray and the syringe were similar, the researchers reported.

Researchers reported differences in times to maximum concentration, which included 14.9 minutes for the autoinjector, 20 minutes for the opposite and same nostril nasal spray doses and 45 minutes for the manual syringe.

“When we initiated the study, we estimated that the 13.2 mg intranasal dose would be roughly equivalent to or slightly better than the 0.3 mg intramuscular autoinjector from a pharmacokinetic standpoint,” Dworaczyk said. “What we saw was a highly favorable pharmacokinetic profile with a rate of absorption as good as an EpiPen (Viatris/Mylan Inc.), but with a higher and more prolonged therapeutic plasma level compared to the EpiPen.”

Intranasal and autoinjector administration achieved similar effects on blood pressure and heart rate, the researchers continued.

Also, there were no serious or unexpected adverse events with the nasal spray, which the researchers called safe and well-tolerated. The researchers reported 219 events experienced by 74% of the participants in cohort 1, with 181 considered mild, and 105 events in cohort 2 experienced by 66% of the participants, with 103 considered mild.

Twenty (30%) of the participants in cohort 1 reported headache. Also, eight (16%) of the participants in cohort 2 reported mild vomiting 1 to 4 hours after receiving the single-nostril dose, which the researchers attributed to potential swallowing of nonabsorbed epinephrine.

Conclusions, next steps

Based on these findings, the researchers said the spray addresses the unmet need for needle-free, convenient and effective self-administration of epinephrine in acute anaphylaxis management.

“Well over 700 participants to date have been dosed without any serious or unexpected adverse events,” Dworaczyk said.

Bryn Pharma is now working on the new drug approval application for the epinephrine nasal spray that it will submit to the FDA.

“We are working against a full development plan for Utuly over the next several years including pursuing a pediatric indication, product enhancements and international regulatory filings,” Dworaczyk said.

“The need for this innovative product is great, and we’re optimistic that we will be able to deliver on our promise to patients in the near future,” he said.

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