番茄社区

WASHINGTON -- Although FDA approval has eluded the intranasal epinephrine spray ARS-1 (also known as neffy), it continued to build its case with findings of resolved allergic symptoms in children and teenagers undergoing an oral food challenge, and with a separate study showing that it maintained its potency under extreme temperatures.

In a small observational study, one intranasal epinephrine dose administered immediately after the observation of a grade 2 allergic reaction resulted in all 15 pediatric patients being able to skip a second dose of epinephrine within 15 minutes.

It took a median of 16 minutes for grade 2 reactions to fully resolve to grade 0. Gastrointestinal, respiratory, and skin and mucosal symptoms all began to decrease within the first 5 minutes following the intranasal administration, reaching full resolution in a median of 15, 15.5, and 35 minutes, respectively, reported Motohiro Ebisawa, MD, PhD, of the Clinical Research Center for Allergy and Rheumatology at NHO Sagamihara National Hospital in Kanagawa, Japan.

Importantly, one patient did develop a biphasic allergic reaction approximately 2 hours and 45 minutes following administration -- they were subsequently treated with epinephrine, Ebisawa said at the American Academy of Allergy, Asthma & Immunology (AAAAI) annual meeting.

The study marks another step in the epinephrine nasal spray's quest to win FDA approval.

Ebisawa told 番茄社区 that the various symptom improvements following administration were "quite similar to that of intramuscular" treatments such as the epinephrine injector pen (EpiPen) or prefilled syringe (Symjepi). "We are quite sure that this really works well for anaphylactic patients."

A total of 15 pediatric patients were included in the study, all experiencing grade 2 or higher allergic symptoms induced by an oral food challenge, leading to 18 observed reactions. Patients ranged in age from 6 to 17 years. Participants received a 2.0-mg dose of the intranasal product if they weighed less than 30 kg (n=6), otherwise a 2.0-mg dose (n=9).

The one patient with grade 2 cardiovascular symptoms resolved to grade 0 at 32 minutes after intranasal administration (no grade 1 exists for these symptoms).

As for safety, 10 patients had a treatment-emergent adverse event: six deemed nasal spray-related and four judged to be a result of the oral food challenge and unrelated to treatment.

Developer ARS Pharmaceuticals had tried and failed last year to get FDA to approve the product as the first non-injectable treatment for type 1 allergic reactions such as anaphylaxis. Despite a favorable endorsement from the FDA's Pulmonary-Allergy Drugs Advisory Committee for use in adult and pediatric patients, the agency ultimately requested that an additional premarket study -- on repeat doses under allergen-induced allergic rhinitis conditions -- be performed before approval may be considered again.

ARS Pharmaceuticals stated that it would submit a formal dispute resolution request to appeal the agency's decision, as well as resubmit the application to the agency likely some time in the first half of this year.

If the intranasal product is approved on the company's second try, it would be the first needle-free form of epinephrine.

While allergen avoidance is often used to prevent type I allergic reactions, epinephrine remains the first-line emergency treatment in the event of a reaction. Barriers to use include, however, a fear of needles or issues surrounding correct administration that can delay or prevent crucial treatment.

ARS has studied other factors that might deter patients from using epinephrine, and at AAAAI presented other research demonstrating that its nasal spray maintains its potency following prolonged exposure to different temperatures.

Under extreme temperature conditions, for example, the intranasal product maintained its potency numerically better than the autoinjector and prefilled syringe formulations:

• 6 months at 40° C (104° F): -13.9%, -27.5%, and -17.2%, respectively
• 3 months at 50° C (122° F): -8.6%, -41.6%, and -56.6%

"The reason we did this study is parents kept saying that 'We left the EpiPen in the car, [so] we threw it away, we were scared if it got hot.' So we said OK, well let's look at the car temperature," Richard Lowenthal, president and CEO of ARS Pharmaceuticals, told 番茄社区. "How hot does a car get in the summer? It's about 122° [F], about 50° C. So we said, 'let's store it for 3 months at 50° C.' At 3 months at 50°, neffy passes spec."

Under room temperature conditions for 6 months, the intranasal product dropped 7.7% in potency, while the autoinjector's potency dropped 4.9% and the prefilled syringe formulation dropped 10%, the study showed.

Current regulatory specifications for an epinephrine product's shelf life allow for a 20% reduction in potency.

Lowenthal noted that while allowing the intranasal product to freeze isn't ideal, as it will not be available for immediate use, it can still be thawed for use later on.