Welcome to the fourth episode of the “Allergy, Asthma & Immunology Innovations Podcast.” This podcast episode is titled “New Ways to Administer Epinephrine – What is On the Horizon?” It explores alternatives to giving epinephrine with an auto-injector. A new epinephrine nasal spray and a sublingual film containing epinephrine are nearing approval.
The podcast is a collaboration between Allergy & Asthma Network and The Itch Podcast. It’s hosted by The Itch Podcast’s Kortney Kwong Hing and board-certified allergist and immunologist Payel Gupta, MD.
In this episode, Kortney and Dr. Gupta are joined by David Golden, MD, board-certified allergist and immunologist in Owings Mills, Maryland, associate professor of medicine at Johns Hopkins, and expert in anaphylaxis and insect sting allergy.
Allergy & Asthma Network thanks Aquestive for their sponsorship of this podcast.
You can listen to or download the podcast on ItchPodcast.com for listening anytime, anywhere. The podcast can also be downloaded at:
Episode 61 Timestamp overview
- 2:45 – New types of ways to administer epinephrine
- 4:28 – How technology enables new epinephrine administration methods possible
- 5:35 – Epinephrine nose spray
- 6:00 – Sublingual film
- 6:17 – How do we know these new methods work?
- 7:10 – How to get FDA approval for new devices?
- 9:35 – Why do we need new types of epinephrine devices other than needles?
- 11:40 – Hesitancy to use an auto-injector
- 13:13 – The challenges faced to get patients and doctors to trust these new methods
Full Transcript
Kortney Kwong Hing: You’re listening to The Itch, a podcast exploring all things allergy, asthma and immunology. I’m your co-host Kortney, a real-life allergy, asthma and eczema girl.
Payel Gupta, MD: And I’m your second host, Dr. Payel Gupta, a board-certified allergy, asthma and immunology doctor. Kortney and I hope to balance each other out so that we get you all the information that you want and need about allergies, asthma and immunology.
Payel Gupta, MD: And I’m your second host, Dr. Payel Gupta, a board-certified allergy, asthma and immunology doctor. Kortney and I hope to balance each other out so that we get you all the information that you want and need about allergies, asthma and immunology.
Kortney: This is our second episode in the Allergy, Asthma, and Immunology Innovations podcast series, in collaboration with Allergy & Asthma Network, exploring anaphylaxis and epinephrine. This episode is sponsored by Aquestive.
Today, Dr. David Golden joins us once again and walks us through the new methods being developed to administer epinephrine. It looks like, my friends, needles may not be your only option very soon.
Because some of the information we discuss in this episode may be time sensitive as many of these new methods are undergoing FDA approval. I wanted to let you know this episode was recorded mid-October 2023. If you missed the first episode we did with Dr. Golden about anaphylaxis and epinephrine, I can highly recommend you check it out for a great foundation on why it’s important to understand this topic when you have allergies. I personally learned so much. It’s scary how long I went without knowing some of this information.
Finally, We’re going to bring you one more episode about anaphylaxis, anxiety, and the risk factors that may increase your chances of a severe allergic reaction. So stay tuned for that.
A little bit about Dr. Golden before we jump in, he is an associate professor of medicine at John Hopkins where he directed a program of research studies on insect sting allergy and anaphylaxis for 30 years. He has published numerous research articles, chapters, and review articles. Dr. Golden is a contributing author to several of the practice parameters developed by the joint task force and is on the editorial boards of several major allergy publications. He has worked as a consultant for Aquestive.
Now let’s dive in.
We’re here today to talk about epinephrine, and the only way we know that you can get epinephrine is through an injection. But not only are we afraid of anaphylaxis, there are lots of people who are also afraid of needles, and their only defense is auto-injectors. So that’s one reason I would think, obviously, we’re thinking about different routes of administration for epinephrine.
So what research are we looking at? Is there something more than just an auto-injector in our future?
Dr. Golden: There is. We’re very hopeful of that. I’m very excited about the research that’s been done by several groups, and we’re seeing more reports of interesting research on ways to administer epinephrine that I’m sure we’ll see more of in the future.
These range from nasal spray forms of epinephrine. In fact, this month’s issue of the Journal of Allergy has a report on a dry powder nasal spray different from the other nasal sprays that we’ve been hearing about. So there are more than one form of nose spray that we’ve seen research on for epinephrine, for treatment of anaphylaxis. We’ve seen research on a sublingual film, a little film that you put under your tongue and it dissolves the epinephrine into your system.
We’ve seen … we’re not hearing so much about this yet, but having looked into it, I’m aware of at least 2 groups and possibly more that are looking into inhaler forms of epinephrine. I don’t know if we’ll say that much about it because it’s at a much earlier stage of development. It’s an old idea because epinephrine inhalers have been around and you can get it over-the-counter for asthma.
Primatene Mist is epinephrine. Why don’t you use that for anaphylaxis? There’s old research going back to the 1980s and ‘90s that says you can, but the venerable Estelle Simons – she wouldn’t want me to call her the Godmother of anaphylaxis and epinephrine and antihistamines – she has all of those credentials, actually. She did a study in children and her conclusion for inhaled epinephrine was that it probably works, but people hate using it because it tastes so terrible. And that was the end of inhaled epinephrine 25 years ago until new research has started to look at perhaps new ways of preparing that epinephrine. The exciting thing about these new products is that they’re finding technical ways of overcoming problems.
The problem with epinephrine is that one of its effects is to constrict blood vessels. That’s how it raises the blood pressure, for example, so that’s an effect you want, but what that means is if you spray it in your nose, it’s going to close-up the blood vessels. So how is it going to get into your system if it reduces the circulation. Or you put it under your tongue and it shuts down the circulation, how’s it even going to get into your system? And that’s really what has made it not an option for all of these decades because there was no way to make it work.
And what we’re seeing now is they were conquering this in technical ways of making a pro-drug. That means that it’s not a full epinephrine. They can make it so it gets absorbed before its able to have its effect of constricting those blood vessels. Same with the nose spray. They have made it in a way that it can get into the system.
Now we’re seeing the results of this basic research of, ‘How do you make epinephrine able to get into the system without shutting down the local circulation?’ And with inhalers, they’re also developing new ways of getting it to distribute better within the airways so they can get into the system.
So now we’re able to advance and we’re seeing, in the past several years, research reports on a candidate product nose spray, which many people have heard of because it’s advanced several stages in the research and has been under review by the FDA. As I said, there are other groups developing nasal spray products, but the one product is so far the only one that’s been more completely reviewed by the FDA. There is a sublingual film I mentioned that is also fairly advanced in development, and I’m sure we’ll hear more about that in upcoming publications and studies, and FDA review as well.
The catch that I will get into briefly as far as how do we know it works? I guess that’s the bottom line. That’s been one of the very tricky parts about the development of these new products. As I said early on, no one’s ever proven that the epinephrine doses that we give intramuscularly are the right dose, or that they work, because it’s considered either impossible or simply unethical to do a study on people who are in full-blown anaphylaxis to give them something other than the gold standard. Do you want to be in a study where we’re going to put you into anaphylaxis then give you something to see if it works? Right. How do you prove it works if you can’t prove it works? Well, you have surrogate markers and the FDA has agreed to look at these products.
And in fact, how did newer products that are on the market get approved? So in the old days, if you will, the epinephrine injection was approved because we know it works. These days, you’d have to do a little bit better than that with things like, there are other products, other auto-injectors on the market – how did they get approved? They got approved by showing what’s called pharmacokinetics. Meaning, if the company can prove that if we give you this product, then we can measure the epinephrine in your bloodstream and it goes up fast enough and high enough to be in the range of other things that we know work, like the EpiPen or intramuscular epinephrine … if it’s in that range, then that’s acceptable. There’s still a little bit of nervousness about it – does that guarantee it’s going to work? This is a problem that has not been totally resolved at this point.
There are these products coming along that have had excellent profiles as far as getting into the system. The publications, the scientific research publications that we’ve seen that were presented to the FDA, showing that the epinephrine, whether it’s a nose spray or a sublingual film, these are publicly presented research results that show that the epinephrine level in the blood does go up. It goes up fast. It goes up high. Does that mean these are going to be approved by the FDA? We shall see.
For those of us who listened in or attended the FDA Advisory Committee meeting looking at this, these concerns were expressed and there was a lot of discussion about, ‘Well, we’d like to have studies and clinical trials to show that it really works, but how do we do that with without it being unethical or dangerous?’ These problems have not been totally resolved. I think we will see some new approaches and considerations by the FDA in discussion with the developers as to lead to approval of a product that we can recommend to our patients with confidence and that patients can carry and use with confidence that it’s going to work.
Obviously, time will tell. Right? Because I believe that one or more of these products will be approved in the next year or two. And no matter what studies are done to support it, it’s only going to be the real-life use that is going to tell the story. We have a lot of confidence in this because of what we’ve seen, the blood levels, and the effects that not just how much is in the blood, but does it raise the blood pressure? Does it increase the pulse? Does it do what epinephrine is supposed to do. The answer is yes, it does. So that’s why I feel pretty confident that we’re going to see FDA approval of one or more of these products.
But that gives you a picture of what kinds of things are in development and what it’s going to take to get them approved and why we think that they will work. The other aspect of this is, you know, why do we need this? And we need this because many of the things we’ve been discussing about the limitations of the current products. Why don’t people carry them? Why don’t people use them? Well, because people are afraid of needles.
There are multiple studies of anaphylaxis that show 83% is the number that we see, interestingly, in several of these studies of people who had anaphylaxis, people who had been prescribed an epinephrine injector who should have used their epinephrine injector, but didn’t. Why? Well, because they weren’t carrying it or they were afraid to use it or because they thought they’d wait a little longer and see if they get better or because they were afraid of needles, or because they didn’t want to go to the emergency department. Right? We’ve heard all of those things.
But many of those things could be overcome if it wasn’t a needle and if it wasn’t cumbersome. If it was easy to carry, easy to use, and people weren’t afraid of it, maybe they would carry it and use it, use it early and successfully. So we’re very excited about the research and these products, but we respect the FDA’s approach of wanting to have confidence that it’s going to work, and that’s kind of where we’re at in this development process.
Kortney: What you said makes me think of using a rescue inhaler. There’s no hesitation whatsoever to use a rescue inhaler, but the moment you think, ‘This is a needle,’ you’re just like, ‘Maybe not,’ even though you know you probably need it. That’s a really interesting reason as to why we want to overcome that fear of using epinephrine, and therefore, let’s just make it normal like a rescue inhaler.
Dr. Golden: I think that’s such a great way of putting it. Rescue epinephrine. Use it if you think you might need it. Again, there’s that balance of not wanting to overuse it, and presumably cost will be a factor more so than taking a puff or two of your inhaler. But it really is a great way of putting it, and that’s the way I’d like patients to think of it, that they shouldn’t hesitate to use it knowing also that they can take a second dose if the reaction is getting worse, like you would with your inhaler.
Dr. Gupta: And I think that in general, anything that comes in needle form just feels like it is a bigger deal for patients, of course, because that’s just not a normal thing that patients necessarily always need to do is inject themselves, where diabetics do that, other disease states do that. But in general, it always feels like a bigger deal. And so that, I think, is the number one reason that we’re hoping for alternative therapies and alternative forms for patients that work.
But, again, it is all a complicated topic because the FDA wants to have proof that it works. But as Dr. Golden said, it’s very difficult to overcome some of those barriers and, you know, doing a study where you’re giving somebody two different forms of treatment and seeing if it works or not.
Dr. Golden: I’m going to just add one more thing, and there are probably ways of doing studies that wouldn’t be as crazy or risky as what it sounds like to do research on anaphylaxis. But it’s maybe important to point out that this whole approach of using those sprays or sublingual films in place of injections is not new or unique to epinephrine. We’ve seen this in seizure medications, in Naloxone, of course. Right? And even anti-anxiety medications, you can get sublingual now.
So the whole idea of having something that works quickly, easily, and effectively as a nose spray or sublingual film is tried and proven. We just have to try and prove it with epinephrine.
Kortney: Do you think that it will be hard to gain trust in these new ways to take epinephrine in patients?
Dr. Golden: Yes. And doctors too. They’re always – we call them late adopters as far as new things and being ready to adopt new things versus waiting until a year or 2 or 3 goes by and we get reports of how it has worked out for people. Depending on what kind of studies are done, how can doctors have confidence, how can patients have confidence? That will come with time, but initially, yes, it’s going to be a factor. I guess my thinking on that, and I thought about how I will approach that with patients, I would especially be targeting some of these situations we’ve been talking about, whether it’s teens or adults or children or caregivers, that if they’re not carrying their epinephrine, or we know they didn’t use it when they should have it. The people who carry it and don’t worry about it, they have used it and use it properly. They may be happy to have an alternative, but they’re not the ones who need it the most.
It’s the people who don’t carry it, don’t use it, don’t use it early enough, because they’re afraid. If you’re not going to carry it and not going to use it, then you may as well have this alternative. You’re going to ask me whether I know for sure it works as well, and I’m going to say I’m pretty sure, but I know it’s going to work better than not using it. I think it’s going to be an easy sell to the people who need it the most.
Dr. Gupta: And I also think that it is going to go on that. You know, doctors have to be ready to accept it. And once doctors are ready and are accepting of it, then inevitably we can help patients understand that it’s effective. And it all comes from the doctor, I think, personally, because if doctors don’t believe it works, then obviously their patients aren’t going to even be told about it or recommend it. And so it’s going to be a whole process. And I personally am always a late adopter for everything. I always like things to be out in the market for at least a year before I start recommending it to my patients, and that’s purely because I do what I would want for myself. And I personally am not the first person to step in line to get a new medication or treatment until I’ve seen it used.
Dr. Golden: I think that’s the case for the majority of clinicians.
Dr. Gupta: Great. Thank you, Dr. Golden.
Dr. Gupta: Thank you for listening to today’s episode. Remember that all information you hear today is for informational purposes only and are not intended to serve as a substitute for the consultation, diagnosis, and or medical treatment of a qualified physician or healthcare provider. And also, don’t forget to subscribe to our podcast.
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