Research presented at the AAAAI annual meeting demonstrated the efficacy, safety and stability of several epinephrine nasal sprays and a new sublingual film.
Needle-phobic people with life-threatening allergies can look forward to alternative epinephrine delivery methods that have shown equivalence with autoinjectors.
Several studies presented at the American Academy of Allergy, Asthma and Immunology (AAAAI) 2024 annual meeting presented by companies that manufacture non-injectable modes of administration have confirmed the pharmacokinetic and pharmacodynamic equivalence of nasal epinephrine sprays with standard of care autoinjector pens in healthy adults and in children.
While autoinjectors are extremely effective when used correctly and in a timely manner, avoidance due to pain and patients’ fear of needles are significant obstacles. It can mean people delay using them until an anaphylactic reaction becomes severe.
A survey of over 300 allergists, paediatricians and primary care providers determined clinicians were well aware of these issues and regarded the possibility of a needle-free alternative as a Very Good Thing.
More than three-quarters of those surveyed agreed that patients would prefer a needle-free formulation and would be more likely to carry it, use it and use it faster.
This survey was conducted and presented by ARS Pharmaceuticals, the maker of neffy nasal epinephrine spray, so perhaps we shouldn’t be too surprised by the positive findings.
There were several other presentations on neffy at the conference, including a Japanese study on children experiencing anaphylaxis following oral food challenge.
Fifteen children aged six to 17 years were given neffy doses appropriate to their weight with complete resolution of anaphylaxis symptoms in a median 16 minutes (range 1–90 minutes) and no more than a single dose required.
One patient had a biphasic reaction almost three hours after initial dosing and required additional treatment. Seven of the patients experienced mild to moderate adverse events which resolved quickly.
Apart from pain, the stability of the autoinjector products is another sticking point. People are required to carry them at all times, which means potentially exposing them to temperature extremes, such as accidentally being left in a car on a hot day.
In a late breaking abstract, researchers representing ARS Pharmaceuticals presented data on the potency of three epinephrine products – neffy epinephrine nasal spray; and EpiPen and Symjepi brand autoinjectors – after being subjected to extreme temperatures.
Stability was assessed at 50°C (car temperature) for three months and 40°C for six months, with 25°C the reference temperature.
The potency of the two injectors deteriorated by more than 40% in the 50°C conditions, compared with less than 10% for neffy. Change in assay results over six months at 40°C/75% relative humidity was -27.5% (EpiPen), -17.2% (Symjepi) and -13.9% (neffy).
“Neffy (epinephrine nasal spray) was more stable than injection products and remained within shelf-life specifications for potency even after 3 months under extreme temperature conditions (50°C),” wrote the authors, led by Dr Richard Lowenthal of ARS Pharmaceuticals.
“EpiPen and Symjepi showed rapid and extensive degradation and were subpotent at these extreme temperature conditions after a short period of time,” they added.
The authors pointed out that the shelf-life of injector products is 18 months, whereas the expected expiration period for neffy is likely to be 24 months.
Moving beyond neffy, in another late breaking abstract, Orexo AB presented data showing that the Swedish pharma’s powder form of epinephrine, OX640, had clinical equivalence to and superior stability over autoinjector epinephrine.
The stability of the two formulations was tested at 40°C, 75% relative humidity over 12 months, with the powder formulation suffering less than 1% degradation compared with around 30% for the injector formulation.
They also compared epinephrine absorption from the two formulations in 40 healthy volunteers and reported that the bioavailability (peak, early and total plasma exposure) and haemodynamic response (blood pressure and heart rate) was comparable.
“The nasal amorphous powder technology 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,” said clinical pharmacologist Martin Jönsson of Orexo in a statement.
Bryn Pharma, a US company whose sole mission is to provide “an affordable, needle-free epinephrine spray” also presented data demonstrating that the pharmacokinetics and pharmacodynamics of its NDS1C product were comparable and non-inferior to an autoinjector.
Finally, we come to a different needle-free form of epinephrine.
A sublingual dissolvable film containing a novel prodrug of epinephrine is under development by Aquestive Therapeutics. Anaphylm is the size and weight of a postage stamp and when placed under the tongue can provide rapid delivery of epinephrine, the company says on its website.
Pharmacokinetic and pharmacodynamic data demonstrated delivery within the range of two different autoinjectors and a manual epinephrine injection, with the authors concluding it shows promise as a viable needle-free alternative for treatment of Type I allergic reactions.
Of all the needle-free products in development, neffy appears to be the closest to FDA approval. ARS Pharmaceuticals submitted an application last year, but the FDA has requested a repeat-dose study comparing it with epinephrine injection under allergen-induced allergic rhinitis conditions. The company has stated that it expects approval by the end of this year.
All in all, an injection-free future looks promising.
“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,” said Mr Jönsson.
