ARS Pharmaceuticals is developing an intranasal spray that will deliver epinephrine, promising an “easy-to-use, needle-free, convenient and more reliable treatment for severe allergic reactions to food, medications and insect bites that could lead to life-threatening anaphylaxis.”
There are a number of questions surrounding the nasal spray formally known as ARS-1, now named Neffy™. Is the epinephrine absorbed as completely via Neffy as it is via traditional injection into the thigh muscle? Is it absorbed as quickly? What if the patient has a stuffy nose from the allergic reaction or a cold?
In a study that would have been presented at the AAAAI 2020 Meeting this week before the conference was canceled, epinephrine plasma levels were measured before and after nasal congestion was induced by a pollen challenge and the pharmacokinetics of epinephrine administered via nasal spray were compared to intramuscular and subcutaneous injection.
36 adult subjects with history of allergic rhinitis (hay fever) randomly received 1mg of epinephrine intranasally or 0.3mg via intramuscular and subcutaneous injection in a cross-over study design.
After the induction of allergic rhinitis by introducing pollen, all challenge-positive subjects received 1mg epinephrine via nasal spray and a subset of 23 subjects received 0.5mg epinephrine via intramuscular injection. Safety assessments included vital signs, adverse events, nasal irritation, and pain.
Under normal nasal conditions, the intranasal administration of epinephrine resulted in plasma levels that were the bioequivalent of a 0.3mg injection but were absorbed more rapidly, reaching a baseline of 100pg/mL in 9 minutes vs 20 minutes.
The absorption of intranasal epinephrine in patients experiencing rhinitis symptoms proved even faster than under normal nasal conditions and increased the total absorption to the bioequivalent of a 0.5mg injection.
The intranasal spray was well-tolerated and any resulting pain/irritation was mild.
The researchers concluded:
Edema [swelling] and congestion does not interfere with the absorption in IN [Intranasal] epinephrine (1mg ARS-1). In fact, rhinitis symptoms appears to enhance IN absorption resulting in Epi Cmaxsimilar to 0.5mg IM. ARS-1 under normal nasal conditions was bioequivalent to 0.3mg IM with more rapid absorption and significantly better hemodynamic responses.