A Primer on neffy for Primary Care: Q&A with Leading US Allergist Thomas Casale, MD

Patient Care: Would you talk about the key factors that have driven the research behind neffy, from the clinical and the scientific perspective?

Thomas Casale, MD. The key driver of this whole program and other alternative non injectable means for administering epinephrine has been patients. Patients have been clamoring for a means to deliver epinephrine rapidly, effectively, but without using a needle. So, in this particular program, the FDA asked for a bracketed approach for PK (pharmacokinetic) and PD (pharmacodynamic) data. So, what they had to do is to show that the epinephrine concentration as well as changes in blood pressure and pulse were in between that which you get from an epinephrine auto injector like EpiPen and manual injection of epinephrine with a needle and syringe intramuscularly.

PC. How significant an issue is the reluctance to use an auto injector or a needle and syringe for treatment of a severe allergic reaction—for patients and for caregivers as well.

Casale. I'm glad you brought up caregivers, because you could imagine, as a parent, if you have a very young child, you're already anxious because the child's having an acute allergic reaction, but to try and inject that child with the needle, and we see in many kids they are clearly afraid of needles, and possibly trying to restrain them, is a real problem. And adults also are reluctant to use it on themselves because they're afraid of a needle. There are other problems as well, in that the devices are rather big, so they're cumbersome to carry. And there have even been a number of cases where the person is in a panic, and with an EpiPen, for example, they hold it backwards and inject their own thumbs. And that's a real problem as well. So, there's lots of different reasons why people don't use epinephrine appropriately, but I think needle phobia is clearly one of the biggest.

PC. What are the risks of not using epinephrine quickly during a type 1 allergic reaction?

Casale. We always say, “epi first and epi fast.” So, what we've learned is that if you have an acute anaphylactic reaction, the quicker you treat, the less likely you are to have a worse outcome. So, consequences of delayed treatment include an increased risk of needing a second injection, hospitalization, or so-called biphasic anaphylaxis, which means the reaction is over and then several hours later it recurs without any other exposure to the allergen. And then finally, fatalities are a potential consequence although it doesn’t happen often, but the delay in epinephrine use clearly poses a risk for that.

PC. Neffy has both portability and durability advantages over injectable epinephrine that may be beneficial for patients and for clinicians.

Casale. I agree, because the container is smaller, the product is less sensitive to sunlight and heat, and it's got a longer shelf life. So, I think all 3 of those things will make it much easier for patients to carry as well as use.

PC. What do you anticipate the uptake of neffy will be by clinicians and the acceptance by patients and caregivers as well?

Casale. I want to stress that epinephrine autoinjectors, or any other device that delivers epinephrine, is still very effective. And if a patient is happy using the autoinjector, that's fine. We know it's going to work. But there are a lot of people with severe allergy that don't want to carry it and don't want to use it. So shared clinical decision making, I think, is going to be very important, informing patients about this option and giving them the choice of whether they want to use this or not.

PC. Epinephrine has been available as an injection for the life of the product. Do you foresee some educational challenges, but also opportunities with clinicians and with patients as neffy is rolled out?

Casale. I think both challenges and opportunities. I think there is a perception among a lot of people that if you inject the medicine, it's going to be more effective. And I think educating them that this should be as effective as injectable epinephrine is going to be important. And if they're not as concerned about using a needle and self-injecting or injecting a child, we hope that with education, they'll be more likely to use the nasal spray and use it more rapidly, so hopefully that will prevent untold problems with an acute allergic reaction.

PC. Are there any nasal conditions that clinicians should be aware of before recommending neffy?

Casale. The FDA actually requested a couple of very interesting studies. In one, neffy was used under conditions of an upper respiratory tract infection, because there was some concern about whether it would still be effective. And it was. The the PK and PD data, both for single and dual doses, looked good. In the second one the question was what if someone has allergic rhinitis or a fever and is very congested? Well, that too was looked at in nasal allergen challenge models. And again, the PK and PD data for single and double doses were very good, so I don't think it's going to be an issue. Remember that this is the same devices used for intranasal administration of a number of medications, including Narcan.

PC. Is there anything you’d like to add about neffy and its use for treatment of type 1 allergic reactions?

Casale. I would like to point out that there are patients who delay using epinephrine because we always used to say, “If you ever have to use your epinephrine, you have to call 911,” and we now know that that's probably not needed. And in fact, the new guidelines suggest that that is not necessary. If you effectively treat the acute reaction and you have good recovery and support at home in case there is recurrence or difficulty, you don't necessarily have to call EMS. So, between having an option that you could use very easily without a needle, and not having to call 911 necessarily, unless you're having a severe reaction, we hope that people will be able to better manage this on their own and have good outcomes.

Thomas B Casale, MD, is professor of medicine and pediatrics and chief of clinical and translational research at the University of South Florida Division of Allergy and Immunology in Tampa. He is a past president of the American Academy of Allergy Asthma and Immunology and was executive vice president for 10 years. He has served on the board of directors for the American Thoracic Society, The World Allergy Organization, and the American Board of Allergy and Immunology where he was also chair.