Neffy is a revolutionary needle-free emergency epinephrine device where, rather than jab your thigh with a needle during a reaction, you simply spray neffy into a nostril.
Since August, when the FDA approved Neffy, you, our readers, have had many questions, including how it was developed and tested, its safety profile, how nasally delivered epinephrine compares with syringe delivery, its temperature sensitivity and time to expiration, etc.
So went straight to the source and asked Richard Lowenthal, CEO of ARS Pharma — the company behind neffy — to come on for an interview to answer all these questions and more.
Here follows the interview in its entirety:
Transcript
Dave Bloom, CEO SnackSafely.com: Hi, I’m Dave Bloom, CEO of SnackSafely.com. If you follow our blog, you know we cover all things food allergy.
But one of the topics we’re most concerned with is the emergency epinephrine market. This past August, the FDA approved the world’s first needle free emergency epinephrine device. It’s called neffy and it’s from ARS Pharma. Now, since since the FDA approved it, we’ve been getting tons of questions from our readers wanting to know everything about how it was tested, the research behind it, as well as temperature sensitivity, time to expiration… all those questions. So we decided to go right to the source, and we invited the CEO of ARS Pharma, Richard Lowenthal, to come and join us and answer all your questions that we’ve been compiling over the past number of months. So here is that interview and I hope you find it informative.
Thanks so much.
Rich, thank you so much for joining us today. Appreciate you coming on and talking about neffy. Yeah thanks Dave. Great to talk. So please do us a favor. Introduce yourself to our audience. Tell us a little bit about your career and that kind of thing.
Richard Lowenthal, CEO of ARS Pharma: Okay. Sure. So, Richard Lowenthal, I’m the CEO and president, of ARS Pharmaceuticals, that developed neffy and also one of the founders of the company. So, just my background. I mean, I’m a biochemist by training, went to graduate school for biochemistry and organic chemistry, and then worked in the industry very shortly and then went to the Food and Drug Administration. So I worked in discovery and then went to the Food and Drug Administration.
So I was at the FDA about six years early in my career. It was a great experience. Really learned how the FDA operated and was able to see a lot of different products. At the FDA you basically see what a lot of different companies are doing, and it’s a great way to learn and also to get that perspective, from their side.
And then, after that, I went into industry. I worked at a small pharmaceutical company that was jointly owned by Mylan and Watson at the time. We developed prexol for Parkinson’s disease and a medicine for depression. And then, I was at Johnson Research Foundation (Janssen in English) and worked there for about nine years in various different roles, including being global project leader for Risperdal and Consta, which were their lead anti-psychotic products at the time.
And then, when I moved to California. I was in some small companies, and I would say, you know, in around 2006, 2007, I started a clinical research organization in San Diego, and we were the ones that worked on a lot of the nasal sprays that were approved. We got Narcan Nasal approved.
We worked on Tosymra which is a sumatriptan nasal spray that uses the same absorption enhancing technology we’re using for neffy. And we also worked on Valtoco, which is a product for acute repetitive seizures. So epileptic seizures that don’t stop. And with Valtoco, we also used the Intravail technology for absorption enhancement.
And so that’s when basically we were working with the company Aegis that actually owns the Intravail compound. And our sera was helping them with their drug master files to the agency. And what essentially… at the time, I just had basically asked the Aegis people if anybody had licensed that technology for epinephrine because epinephrine is not absorbed intranasally without really seriously damaging the nasal mucosa.
So to get penetration, it does not penetrate the nasal mucosa, and so you need something to get it through the nasal mucosa. So we agreed to acquire a license from Aegis for the technology to use with epinephrine, and that’s how we started ARS pharmaceuticals at that point, in order to raise money and be able to develop the product as an independent company.
So that’s, that’s some of my background. And then I’ve been, of course, CEO and president for the last eight years. For good or bad, it took us eight years to actually get to this point with neffy. So it seems very simple, but it’s actually not., and part of the reason is we not only had to develop the formulation and do all that work, but we also had to find the right dose and negotiate with regulators, the best way to get neffy approved, and that was actually not easy. I think at this stage, the regulators has set a very good standard to where we can assure people that neffy is always in an exposure — or even under worst case nasal conditions like you’re having a very severe rhinitis attack — that it would still give blood levels that are efficacious, but that even under also under any kind of circumstances that we could we can imagine or test that FDA asked us to look at, you wouldn’t get too much epinephrine.
And and to be honest with you, I think, in my experience, the regulators were maybe more concerned about excess exposure than than low exposure. They certainly don’t want anything that’s not efficacious. They certainly want enough epinephrine to work, but they’re also very concerned about too much exposure. And one of the reasons, for people to understand — that is that when we test neffy — we’re testing it in a clinical environment.
And people that come into the clinic are relatively healthy. We don’t bring in people with cardiovascular disease or anything like that. In the real world, that’s not the case. So FDA was very sensitive that too much epinephrine… If it’s more than what we’ve known to be safe with, for example, EpiPen. And we know that that with two doses of EpiPen, that that’s safe for community use setting.
They didn’t want to see us get to an exposure that would exceed that because they’re more in an environment where they’re not sure if we’re going to be safe or not in the real world. And that’s really how we developed neffy to be within that band of safety and efficacy.
Dave: So from all your experience, it sounds like you’ve been working for 150 years.
Richard: Thank you.
Dave: But, I imagine that your experience with the FDA really informed you moving forward to get FDA approval for neffy Sure.
Richard: Yeah, absolutely. I think I think FDA was exceptionally careful with this product. And as I mentioned, for two real reasons. One, because of that narrow therapeutic window. So it’s not like naloxone, where to be honest with Narcan, you could not overdose somebody with naloxone.
You can give them as much naloxone as you want and the worst thing that will happen is they’ll get nauseous, but you can’t hurt them. So for that type of drug, you can err on the side of overdosing on high exposure, with epinephrine, you can’t do that. You have to be in that narrow range of being efficacious, but not too much.
So FDA, it was quite difficult, I would say, compared to any other product I’ve worked on like this, where we couldn’t do a clear efficacy study, like we do with some drugs, but in this case, we couldn’t induce anaphylaxis in somebody to do an efficacy study off course. So, they were very, very difficult in this product, more so than any others.
But you have to be perseverant you have to work with them. They are the the authority that has to make the final decision. And so having the experience I have with regards to not only being in FDA, but working with FDA at multiple different companies, I think that helped with us being able to work through the issues they had negotiated with them.
And even though we’re not pleased with some of the things they asked for, especially at the end where we thought we had agreement and then they delayed again by roughly ten, 11 months, because they wanted to be absolutely sure. I think even while we don’t agree with that, we understand their perspective and what they were trying to accomplish.
We would have loved to have this to everybody a year ago, but you know, they wanted to be absolutely sure. And that should also give people reassurance that FDA was not, you know, just approving this. They were very careful in their approval. And I think, if any of your readers have not looked at what FDA wrote about the approval in their press release, I think it’s worth them going and looking at what FDA’s final opinion was, that they expressed in their press release because they really believe neffy will bring a lot of benefit to the community as well.
Dave: We’ll make sure we add that to this interview on our blog so folks can click right over. Can you just spend a couple of minutes talk about ARS the company, tell us a little bit about where you’re based, how many employees you have, maybe some other initiatives you have in the pipeline right now?
Rich: Sure. So ARS is based in San Diego, California.
We have about 150 people right now. We’re still growing, of course., but we do have people all over the country. So, a lot of our commercial group is in the Philadelphia area. And then we have, obviously regional, you know, medical liaisons. And we have also regional salespeople that are all over the country at this point that are working with the doctors and trying to get also with patients and caregivers to try to resolve early issues with access reimbursement and things like that. So we have people all over, you know. The company’s initiatives right now… I mean we’re very focused on getting neffy to the consumers and getting access, meaning insurance coverage.
Okay. So that’s a that’s a major objective of ours. We’ll talk in a little bit about how we’re pricing neffy and how we think about making sure it’s available to patients and caregivers. But getting the insurance companies to reimburse and to put it on formulary to make that much easier for patients and caregivers is a major priority of ours right now.
We also, filed our one milligram dose, which is for the 15 to 30 kilogram children. That is under active review by FDA. We anticipate FDA approving that in March. And so that should be available by, let’s say, May of next year. So before summertime, we should be able to be able we should be able to provide the one milligram dose for those smaller children.
And then we’re also working on a dose, which may be 2 to 3 years from now… but we’re working on a dose for children under 15kg as well. We would also modify the device slightly for those smaller children. The device we’re using right now works very well in children roughly four years and greater. When you’re talking about under 15 kilogram children, you may have 1 or 2 year olds.
We want to make sure the device is modified to fit properly in their nose, and it won’t so that it gets into the nose and doesn’t go, you know, get, let’s say doesn’t move when you fire it, when you spray. And so we’re working on that as well to have a dose for those children.
And partly, the European Medical Agency in Europe is requiring that. FDA did not require us to develop the lower dose for those smaller children. But we would obviously introduce that in the United States as well once it’s ready. And then the other thing we’re doing is working on the potential for intranasal epinephrine to be used in treating urticaria.
And, this is not a chronic therapy, but in a lot of people with chronic spontaneous urticaria — even who are on medication and relatively stable — they have what’s commonly called a “flare” and it’s an exacerbation of the symptoms. So they seem to be stable for a month or two and then all of a sudden they have a big outbreak of urticaria, and it’s very irritating, itchy, sometimes painful. In fact, people describe it as painful. And obviously they get hives and rash and it’s very irritating. Epinephrine is exceptionally effective at controlling that, and we believe that an even lower dose — not the dose we’re using for food allergy and venom allergies because there we, we definitely want blood pressure and heart rate increase, because we want that blood pressure support.
With urticaria, we don’t need that. But we also need mainly mast cell stabilization, which occurs at a much lower dose with epinephrine. So we believe we can actually be on the safer end of the exposure and use a lower dose for urticaria, and we’ll be working on that as well over the next couple of years.
So the timeline is a number of years for that as well. Because we’re going to run one more phase 2B study, we call it meeting a safety and efficacy study with control with placebo, mainly to optimize the way we’re going to measure the urticaria event — this flare event — in an outpatient setting so people will do this at home, treat themselves and assess the symptoms at home. So we want to do that as well as assess the lowest dose we can possibly get to. And then we’ll run a full efficacy safety study, a phase 3 study. So we’ll do those two studies before we file for approval.
Dave: And you’ll know it’ll be safe because you already have all the data from neffy and you’re going to be going… we’re going to be stepping down from that.
Richard: Correct, yes.
Dave: Okay, so let’s talk about neffy. Tell me a little bit about — in your words — what what neffy is, how it differs from auto-injectors, what you hope to achieve with the difference with auto-injectors.
Richard: Yeah, sure. So what we’re trying to achieve with neffy obviously is to address a lot of the concerns we’ve heard from patients and caregivers about the auto-injectors.
And I don’t want to be negative about injectors because auto-injectors have been very helpful to this community. And they do work. So they work very, very well. However, there are many people who are very afraid of needles, adverse to needles and especially children. And even in an emergency situation, many people we know either don’t administer their auto-injector or they delay and they wait too long to administer the auto-injector.
And so assuming they even carry it, because they’re also bulky, so carriage, being willing to use it and being willing to use it, as soon as possible after symptoms start, because that’s when epinephrine is the most effective. Really things we are trying to solve for. So neffy is obviously much smaller. It’s easy to carry.
For your viewers also you do not — because we’re getting a lot of questions about this, we specifically discussed with FDA, and the labeling is very carefully worded — that you do not have to keep it in the packaging. It comes with. The device was tested as the separate device, independent of the packaging for stability and all the other criteria we tested.
It only is put in a blister because that’s the machines at the production plant have to put it in something, and they all set up to put it in a blister pack like that. But you can take it out and put it in a convenient carrying case you have or we provide a carrying case. At neffy.com we provide a really nice blue carrying case that you’ve probably seen online.
And we’ll provide that at no cost to patients and caregivers to help them carry it. Now, the only thing the FDA asked is that if you remove it from the packaging, that you keep the instructions handy and keep the instructions either with the device or nearby so you can remind yourself, if necessary how to use it.
And that’s the pamphlet with the instructions for use, and the nice pictures that show you how to use neffy. In the carry case, we give a miniature card that gives the instructions in an abbreviated way and has a QR code to go to the to a video to see how to use it, and also to the website to see anything you want to read about it.
But that was the only ask of FDA is that they they just don’t want you to forget how to use it. So they want you to keep those reminder instructions with you to, remind, remember how to use it when necessary. So obviously it’s easy to carry, we want to facilitate that. Everybody should keep it with you as much as possible.
The higher temperature stability of neffy also makes it easier because you don’t have to worry about carrying it, you know, on a warm day or, you know, if you left it in your car by accident, neffy tolerates relatively high temperatures very, very well. We also wanted to remove the needle, of course, and in doing that, though, you can’t have an alternative where you cause pain.
So one of the great things about the Intravail technology we’re using, which is the nasal absorption technology, is that it doesn’t cause any irritation or pain. The way it works is it’s simply, what I call a very smart soap. It’s not like regular soap. The Intravail can get between the tight junctions of cells and make them looser.
So it makes the membrane porous, but it doesn’t kill cells. It doesn’t hurt the membrane, doesn’t cause pain or irritation. But it makes it more porous to allow the epinephrine to penetrate through very, very quickly. And it happens instantaneously. So it’s really that fast. So that makes this a very unique technology where the other technologies that may give you this kind of absorption actually have to destroy the membrane.
So you have to actually damage the membrane to allow the drug to penetrate. And that causes a lot of pain or irritation. So solvents, or if you use bile acid or things like that, they work. Those things could work, but they’re going to cause a lot of pain and irritation, and we were trying to design something for children.
So, obviously neffy is an aqueous formulation. It’s in water. It’s using the Intravail technology which does not cause pain and irritation. So when you spray it in your nose, some people say they feel the epinephrine. They can feel the epinephrine doing something in their nose. We’ve had some people report a little throat tingling or irritation, whatever you want to call it, but could be tingling or irritation.
But it’s rare, and it’s it’s usually on a second dose. But we wanted something that was very tolerable for children because, again, you have to have something they’re willing to use and use more than once. So if they experience it once, you don’t want it to be a bad experience that they won’t do it again, right,
if they need it again. And then we wanted something very easy to use. The device does not need activation. It’s a single use device. So once you fire it, it’s fired. And there’s no cap or anything. So for those of you who have asked us why is there no cap, it’s because you’re first of all, your nose is not clean.
You’re breathing in dust and dirt all the time. Your nose is designed to filter that out. So if the tip gets a little dirty, it’s not going to hurt you. But we wanted something that’s foolproof, that’s very reliable. You put it in your nose and fire it, and you’re done. And it’s instantaneous, by the way.
And the other thing is, a child cannot sneeze it or sniff it out of their nose. We’ve done studies on both that if people sniffed or sneezed in the clinic, we’ve looked at the data, and it doesn’t really change the absorption of neffy significantly. So it’s really that instantaneous. You just have to get it in the nose and fire it, and it’s done and you’re medicated.
And then finally, I think, we really wanted something that was friendly to people that people were not going to be afraid of, and they’re not going to be intimidated by in a public setting. Because we do want people to carry it and use it as soon as possible. And as I mentioned earlier, the sooner you use the epinephrine, the better the clinical outcomes will be.
And we know that from many, many studies now that there’s less risk of a second dose being needed, symptoms resolve much quicker, so your clinical outcomes, your less chance of being very sick or being hospitalized or even just a chance to work…
Dave: Less chance of of biphasic reactions.
Richard: Exactly. Less chance of biphasic. So the sooner you take it, all the data shows, the better the outcomes and the more likely you are to stop that reaction quickly and not let it progress to anaphylaxis. And it’s even a mantra of some of our doctors we worked with very early on, who were, you know, very well known in this business. When I said to, for instance, Richard Lockey, when I said to him the first time, maybe eight years ago that we were developing this nasal spray to treat anaphylaxis, he said, “no, we’re not!”
He said, “we’re really developing this to treat allergic symptoms as soon as our patients experience them so they never progress to anaphylaxis because we want to prevent that from ever happening.” And so that’s the idea of neffy, is you carry it, you’re not afraid — even in a public place — it’s just putting this in your nose and firing it.
Dave: It’s not like pulling out an auto-injector and injecting yourself in a restaurant.
Richard: Right. And we’re hoping that that makes people’s lives much easier. We hope it reduces anxiety because we know with this disease, you’re out, you want to go enjoy yourself in life.
We don’t want people to intentionally or be, you know, too, how can I say, careless about what they eat. We want people to eat safely. But at least, you know, if you make a mistake, if you eat something or something is contaminated and you have a reaction, you’re going to have neffy with you and you could use it quickly, and you’re not going to have that anxiety of having to inject or inject your child.
And I think that is almost a quality of life, peace of mind type of issue that we think neffy can help people in the community really resolve that fear they have of the needle and of treating themselves with epinephrine. And just one other point on this, I want to emphasize one other thing that FDA did that they were very cooperative about.
And in conjunction with the new guidelines that came out, people have to realize that epinephrine at the doses we’re giving is actually exceptionally safe. So they should not be afraid of the epinephrine itself. I think there’s a myth or a misperception out there due to some of the old legacy labeling — and FDA understands that now — and the old legacy labeling talked about in conjunction with use of this product of epinephrine, seek emergency medical help.
And people misunderstand that to mean that the epinephrine causes you to need emergency help. And that’s really wrong. The epinephrine, the idea that language was, treat yourself immediately and then seek emergency medical help. For the anaphylaxis! For your anaphylaxis, exactly. You’re seeking it because you’re having an anaphylactic reaction. Now fast forward to today with everything we know, and maybe even with some help of Covid — as horrible as that sounds — we’ve learned a lot that when people treat themselves properly with epinephrine, they don’t need to go to the hospital. And so the new language in neffy is very, very different. It’s very independent. Treat yourself immediately. First, signs of symptoms, but very independently and intentionally. FDA separated out language about seek emergency medical help if needed for further treatment of your anaphylaxis.
And really what they’re trying to say there is if you take your epinephrine, whether it’s injection or neffy, so I’ll be fair — It doesn’t matter what route you take your epinephrine — if you take your epinephrine, and it works and the event resolves, there’s really no benefit for you of going to an emergency room. And the time, the stress — and what we don’t want, certainly, and what FDA doesn’t want, and certainly the medical community in new guidelines — is we realize that that fear of going to an emergency room was a reason why people didn’t take their epinephrine. It was one of the actually top 3 or 4 reasons. You know, needle was always number one, but top 3 or 4 was, “I’m not taking it or I’m going to wait till this gets really serious before I take my epinephrine, because I might have to go to the hospital.”
And that’s exactly the wrong thinking, because taking the epinephrine sooner would prevent you from going to the hospital. So now I think the community has gotten to a point where the medical community is aligned, FDA’s aligned, neffy’s labeling is aligned. Epinephrine injection or labeling may change in the future too… FDA may change that. But right now, with that language, you should be taking the neffy immediately.
If symptoms resolve, you’re fine. You can call your doctor, but you don’t need to go to the emergency room — if you really want to, you can — but you don’t need to. And then the idea is, okay, if let’s assume you take it and it doesn’t resolve… the event does not resolve which happens roughly 10% of the time, you need a second dose.
You take your second dose, but then, maybe you want to think about activating emergency help. Or let’s say you have a biphasic reaction later, you take your second dose. You may need to activate emergency health because you don’t have a third dose. And so the way we would think about it is, then it’s probably prudent to get emergency help in case the second dose is also not effective and you need further treatment.
Because as is in our labeling and in auto-injector labeling, you shouldn’t take a third dose without medical supervision. Okay? At that point, they would like you to have medical supervision again because FDA is worried about too much exposure. And they think that should be done under medical professional’s advice. So at that point you may want to think about getting emergency help.
But again, that’s for the anaphylactic event that’s continuing and it’s not resolving quickly. But if it resolves quickly — like 90, 95% of the time, it will — you don’t have to spend your time and money to go to an emergency room and wait for them to look at you and say, “you seem to be fine, go home.”
Dave: And for some people, it’s money that’s the issue.
Richard: Absolutely. Absolutely.
Dave: The ER could be very, very expensive.
Richard: Yeah, it’s very expensive. Often insurance doesn’t cover a lot of emergency room visit costs. So, it’s expensive for the insurance companies too, so they recognize that this is a big advantage of neffy. They’ve been very positive about neffy so far, and we’re hoping we’ll get coverage very quickly.
But insurance companies very quickly — the medical review boards and insurance companies very quickly — understand the issues and that neffy will help people carry it more often, use more quickly. Events will get resolved more quickly with less hospitalization and hopefully reduce the number of emergency room visits, which, by the way, this disease results in about 500,000 emergency room visits a year, which is just astronomical.
It’s, you know, that’s a very large number for almost any disease in this country.
Dave: Yeah, absolutely. I just want to dispel one sort of issue that folks out there are not understanding. Neffy, when you spray it in your nostril — because people are concerned about what if the person is unconscious and you need to administer it to them. How does that work? Well, the you’re not inhaling the drug into your lungs. You’re coating the nasal membrane with the drug. So, you know, is that correct? I just want to make sure.
Richard: Yes absolutely. Absolutely. You don’t… It doesn’t go into your into your lungs, as you said. In fact, it’s designed not to.
By the way, the nasal sprayer we use — which is the same as Narcan’s, the same device — is really designed to spray and deposit on what’s called the turbinates in your nose, which are the organs in your nose that filter in your nasal mucosa, that filter the air. And these droplets are too large to get into your lungs.
So it’s intentionally designed that way. And really intentionally designed to administer to the nasal mucosa. Now, with that said, as you were saying, Dave, you don’t have to breathe. And Narcan is a great example where you’re giving it to people with opioid overdose. They’re very often unconscious, and it works fantastically well. And people wake up in minutes and recover.
But they never actually had to breathe. And so, so that’s really the great advantage of nasal administration. And especially in this kind of disease or even in asthma or other diseases where you can’t inhale. Well, nasal administration gives you that option to administer a drug, and the nasal mucosa is exceptionally good at absorbing drugs, again, once we get penetration through the through the membrane. And the way your blood flow works actually is your nasal mucosa, the blood flow from your nasal mucosa actually goes directly to your heart and distributes through your body very rapidly. So it’s really a great way to administer drugs, and especially for emergency use, which again, Narcan, Opvee are both approved now, nasal products for opioid overdose. Valtoco and Nayzilam are two nasal products for acute repetitive seizures, so emergency treatment of seizures. They work exceptionally well and again, very effective at just the time to administer the speed, the ease of administration. And that’s why for opioid overdose, which is, you know, more life threatening as far as the amount of time you have before somebody could be there with brain damage or die. It’s exceptionally effective because it’s literally… you’re worried about seconds, not minutes in that disease and having a nasal spray like this — a device like this to administer so rapidly — is really very helpful.
Dave: That’s very comforting because, I know that we’re getting a lot of feedback from folks, and there’s a small segment of the population that’s concerned because they see jabbing an auto-injector into your thigh as getting the epinephrine where it needs to go much faster than spraying it into your nostril. And that’s not the case.
Richard: No, it’s not necessarily the case. And again, the the different injection products are very, very different in their pharmacokinetics, we say, and the amount of time it takes. And in fact with needle and syringe — just to give you an example — if the doctor gave you an injection with needle syringe intramuscularly, the data shows that the maximum blood level of epinephrine is at around 45 minutes.
With neffy, it’s roughly 20 minutes. So now with auto-injectors, it can vary anywhere from 10 to 30 minutes, let’s say. So there’s a lot of difference with the auto-injectors that have to do with the depth of the needle, the pressure, all different factors… the way you do it, your technique and how you administer and where you administer it can vary.
Now does it matter…
Dave: Body mass as well.
Richard: Yeah. Body mass as well. Now does it matter? Probably not. As far as we know from the knowledge about use of epinephrine during an active reaction, whether it’s a needle and syringe and you’re having an oral challenge and the doctor gives you a needle, syringe, or you come in an emergency room and they give you a needle syringe or they or the emergency medical unit, EMS group gives you a needle and syringe injection, so it’s 45 minute Tmax.
It works very, very well. It works as well as any of the injections, any of the auto-injectors. So, no matter what that pharmacokinetics is, it may not matter because epinephrine works so rapidly once it’s in the body. That no matter how the pharmacokinetic profile goes, it works very, very well. So that’s what we know.
So that’s why we designed neffy to be in that range. And again we call it bracketing, but we were bracketed by IM needle syringe. So we’re always better than that. And we don’t want to be more than the highest exposure at auto-injector, which tends to be EpiPen. And again, because of the length of the needle and the pressure, EpiPen tends to be a little bit higher exposure.
But we wanted to be in that range where we know it’s efficacious and safe. And that’s kind of was the idea. But you don’t need to breathe in. You don’t need to worry about that. It’s very rapidly absorbed. And, you know, based on our experience in both the clinical trial in Japan in children having anaphylaxis from an oral challenge situation as well as, you know, the anecdotal information we’re getting from people have used it now in the community, it seems to be working very, very well. And as well as injection.
Dave: I want to touch upon that point because that’s very important. So, folks believe that there was no testing of neffy under real world conditions where someone was actually having a reaction, and that’s not the case. Tell us a little bit more about that Japanese trial.
Richard: Yeah. So we we did not need to do a study like that for the United States. At FDA — in the US — FDA wanted to see PK, the way that the drugs absorbed into the blood and also, pharmacodynamic response, which is the way your body responds to the epinephrine, with regards to your heart rate, blood pressure changes.
And so that was sufficient for FDA to be convinced that it’s going to work the same as injection.
Dave: But let me stop it for just a second. Sure. Because originally the auto-injector wasn’t tested with live cases of anaphylaxis. I mean, that’s my understanding.
Richard: Well, correct. In fact, to be very honest with you, none of the auto-injectors, with exception of one, was ever tested, even for pharmacokinetics.
So, EpiPen got approved without any human testing. So it was, way back when… I mean, 38, 39 years ago now, FDA thought an injection was an injection, that there was no difference between one injection and another. They now know that’s not really true because the devices that are used for injection make a big difference. Okay.
But back then, we didn’t know. So FDA approved EpiPen based on just the fact that it’s an injection and they knew IM needle and syringe injection worked. And then, in fact, even Symjepi, which was probably the last of the devices, which is a prefilled syringe type of device didn’t do pharmacokinetics.
Now Auvi-Q did a study, but more for marketing reasons. FDA didn’t require them to do it. It was for marketing reasons. So they did a comparative study with EpiPen. But really, none of those devices even had human data at all. So we’ve done more than 18 studies. The study we did in Japan was driven by the Japanese authorities. The Japanese regulatory authority was fine with the PK and the pharmacodynamic comparisons, but they felt they really wanted to see it used in a patient having a reaction.
So we did a study in Japan with oral challenge patients. So these are children — there was a fairly broad weight range — so some children had one milligram dose, some had two milligram dose depending on their weight. So we tested both doses, and after they had oral challenge, if they had an anaphylactic reaction and it had to be grade two or greater, there were a few that had grade three reactions already.
Grade four is really kind of serious, serious anaphylaxis. So grade three is already pretty serious. One of the children had significant hypertension, in fact, so had cardiovascular reaction. And it worked in everybody. So it was, in all the kids treated in that study, 100% of them had a response on a single dose.
One did have a biphasic reaction later and had to get further treatment later. I think 2 or 3 hours after the first dose, which is not uncommon. And again, you know, the physician, the doctor that did this in, Japan, Dr Ebisawa… very famous guy, he was the president of the World Allergy Organization recently the one prior to the person now. He said in that kind of food allergy, the child had egg allergy, and it’s not uncommon. They have a biphasic reaction. It’s, you know, happens… and again, 10% of the time you need a second dose. So nobody needed a second dose in that study. And it was just the one child that had the biphasic reaction later.
And so we think that was really a good result and outcome. So we, felt that was a really positive study. But again, it wasn’t part of the FDA filing. It was done for Japan. And we anticipate that actually, our partner in Japan will be filing for approval in Japan, probably later this month or early December. So they’ll they’ll be filing in Japan as well for approval.
Dave: That’s terrific. And just to summarize, so this was not just done with PK and PD. We’re talking about actual, real world cases where ethically — it’s important to say ethically because you can’t induce anaphylaxis, you know, just for the hell of it — but these kids were going under, were going through, food challenges where these things happen. And they were given neffy and everything turned out fine.
Richard: Right. And the other thing, we’re getting a lot of positive feedback from now is, so in the United States, after we introduced neffy into the market, we did start a program called “neffy experience.” So, right now, last report I have is about 800 doctors have drug in their hand.
We have 1000 enrolled. So we’re getting everybody their medication. And what we’re doing is we’re actually, giving doctors some neffy to use in their clinic during the oral challenges or immunotherapy. And if they, if the person undergoing oral challenge or immunotherapy has a reaction, that they could treat them with neffy. And the idea that is to give your doctor personal experience with neffy and the way it works, and that it works as well as injection because they’re normally going to use injection, normally needle and syringe, but some will use an auto-injector to treat children or adults if they’re having a reaction from the oral challenge or immunotherapy. In this case they use neffy and they can get that personal experience so that when mom and dad comes in and asks that question, it’s not us or FDA, even. So, FDA says it should be equally effective. It should be interchangeable. There’s nothing in our labeling that says try injection first and then neffy, whatever….
Keep injection with you. They don’t they don’t say anything like that because they’re pretty confident it’s going to work equally well. But now your own doctor can say, hey, you know, I tried this and it works. I can’t tell the difference between how neffy worked and how an injection would work, and that gives them that confidence to talk to mom and dad, talk to the patient and give them that kind of real world experience of their own, that it’s working the same. And if your doctor does oral challenge or immunotherapy, by the way, and they haven’t been in this program, we are planning on expanding it to more doctors and the thousand we have enrolled, and allow more doctors to come into the program and get that experience firsthand.
And then finally, we are doing for FDA what’s called a registry study, where we will do — again, we’re not we’re not sure on the exact number — but roughly 500 or more, where we will we will treat under under a more controlled condition comparing to injection directly and collecting all the data for FDA. FDA was not necessarily worried about efficacy as much as, I think, safety.
I think again, all of our safety data for neffy came from clinical trials with people that were relatively healthy. They wanted they wanted to see real world data with the average oral challenge patient coming in the door, not many restrictions at all. And they they can get better data during an actual reaction.
And that’s what we’re doing it mainly for. But, but we’ll collect efficacy data as well, to reassure people that this is working really, really well, and as well as injection, that it’s really not any different.
Dave: That’s terrific. One of the complaints that we often get with some of the auto-injector, especially with, with EpiPen, is you go to the pharmacy, you get a box, and there’s a 12 month expiration time. The box may have been sitting on the shelf for a while. Maybe you get ten months out of it. Yeah. And then you have to buy a new set. So talk a little bit about the time to expiration when your neffy gets delivered or you pick it up.
Richard: Right. So, typically our expiration period is 30 months for neffy. Okay. Now, we know that past the 30 months, we do not pass at 36 months on some lots, at least past the FDA requirements, right. So, people can argue about whether FDA has requirements are, it’s still effective after that. But from our perspective and FDA’s perspective, they don’t want it used after that period of time.
Okay. Now with that said, that’s from date of manufacturing. Typically you should you should get it within six months of the time it was actually made. So with neffy, you should get at least two years. If it’s beyond two years, you know, it’s probably very infrequent that that would happen. But, you should get at least two years of remaining shelf life on the product.
And it has to do with our formulation. Our formulation is just different. And I won’t get into the technical details, but there are reasons why neffy is more stable and especially at high temperature. So again, we did three months stability at 122 Fahrenheit replicating car temperature in the summer. And that’s a pretty high temperature, where neffy was still stable for the three months.
It was still potent after three months of time at that temperature. So, so we did that because we did hear from from patients and caregivers early on when we talked to them and in focus groups that, “I left my EpiPen in the car, got really hot. I threw it away.” Some people complain they have a habit of it, that they spent a lot of money on EpiPens because they leave them in their car.
So we wanted to give people that reassurance. And FDA allowed us to put that in the label. And it says basically excursions to 122 degrees are allowed. We don’t want you to store it intentionally at that temperature, but nonetheless, you know, all drugs should be stored at room temperature, they’re room temperature storage. But, if it happens, you have peace of mind that it’s still effective.
But you should get at least 24 months, hopefully longer. You know, just depends on how long the distribution channel takes to get. You know, it takes a couple months for us to release it out of the facility, do all the testing and release it. And then depending on how long, you know, gets through distribution, but, you know, but it should be at least two years of time.
And that’s good. Actually, by the way, you know, the other really super benefit is if you have to leave a prescription at the school, you now can leave it for a couple of years. You don’t have to be a place holder for years. And by the way, school nurses really are excited about neffy. We’ve gotten a lot of positive feedback.
They don’t like using injection either. So even on on the kids, they don’t like using injection. And they’re really positive about the temperature stability of neffy that they don’t have to be as sensitive or worry about if it was exposed to warm temperature, and leaving it in the clinic at the school. And, you know, we really hope that without the needle with the safety of neffy, that children will be allowed to hold it at school themselves and not have to leave with the nurse.
It would be a much better situation, especially now school… Some schools don’t even have nurses full time. So if there’s an emergency, having the child have it with them so either they or a teacher or another school adult at the school could help and administer it quickly, I think is a huge benefit without fear of the injector and somebody getting a hold of it or another kid getting it. neffy really can’t hurt you. And one other question that sometimes comes up.
I want to make a comment about this. We even tested neffy if it accidentally sprays in your eye. And and we did animal testing. Again, different regulators asked for different things. This was a request of the European Medical Agency, again, where they wanted to know what happens if it gets in your eye.
We tested in the eye. It causes no harm to eyes. So it really is very safe and can’t hurt people. And we think that’s a major benefit, especially for children. And if they carry it themselves and protect themselves, children. We tested children down to ten years old can easily use nephew by themselves. But parents should assess whether their child is capable.
It could be below ten, and they’re perfectly capable. You could have an 18 year old that can’t do it, you know. So you you should really check that your child is fully capable of using the product.
Dave: But we’re big proponents of kids from the time they start school, at least carrying it with them so that they always have their epinephrine with them. Don’t have to go across the school to go to the nurse’s office or whatever. The child has it. Much more likely for schools to allow children to carry it even younger because there’s no needle involved.
Richard: So exactly. It’s a win, right? Yeah, we hope so. We hope so. We hope that will really benefit kids and not, you know, every once in a while there’s a, there’s a tragedy because a child could not get the epinephrine in time. And we don’t want to see that if we can avoid it.
Dave: And we don’t want to report on it either. It’s, it’s horrific, just the thought of it. So let’s talk a little bit about pricing, both with and without insurance. So tell us about that. Maybe you could tell us a little bit about Blink and what you folks are doing there as well.
Richard: Right, right. So, our strategy here is, our obligation to the community was to try to find a pathway within our medical system — which is a little bit of a complicated system — but to find a pathway so that patients and caregivers would not pay more than they’re paying today for their auto-injector. So for people with insurance… if we get insurance coverage, and right now, again, about about a third of insurance companies appear to be covering right away, the rest are requiring prior authorization, but we’re seeing more than 50% of those prior authorizations approved. So right now, again, prior authorizations are not convenient. The doctor has to sign. You got to get your doctor to do it. I’ll talk about BlinkRx in a minute, but at least if they send the prior authorization to insurance companies, more than 50% are approving.
And then if they don’t approve, you could still appeal that. I don’t have good statistics yet on how that’s going because we don’t have enough numbers yet for appeals. But at least on the first prior authorization within a day or 2 or 3, the insurance companies are approving, and that means you’re covered. If you have that kind of standard commercial insurance where your copays are not very high. So there are plans that have very high deductible co-pays. But if you have a standard insurance, which is about 80% of people out there, it should be around $25. Okay. We have been approached by one insurance company that wants to make the deductible lower for their participants. That’s wonderful. We’re trying to work with them to figure out a way to support that.
But we’re trying to get the copay down to $25. What that means is that, let’s assume your co-pay from your insurance company is $80. ARS is going to pay the difference down to $25. So we pay that out of our portion of the amount of the money that’s being paid. And we pay that back. So we get it down to $25.
And then the average copay, by the way, for comparison of auto-injectors on average is about $40. Some people pay more, some people maybe a little less, but on average, it’s $40 for an auto-injector. Auvi-Q is higher. Auvi-Q… I’m not…. This is a generic auto-injector. So this is the generics. Auvi-Q on average is much higher.
And then, for cash pay… so for somebody who is in a very high deductible plan or somebody who is not insured at all, we wanted to also match what is the average cash pay price for auto-injectors, generic auto-injectors: a generic EpiPen, Amneal, Teva… and that’s about $200. So we price neffy at $199 as a cash pay price.
Now, if in either case, not all pharmacies will have automated systems to get the coupons. So what you want to do — and, you know, I just had some interactions with one person who ended up paying $60 at the pharmacy, and I asked them specifically. They told me they got it, they’re very happy. They paid $60. So I said, oh, why did you pay $60? Did you get the did you get the coupon off the off the website? And she said, no, I forgot. So we don’t want people to forget. I mean you want to go on to neffy.com, you can go on with your with your with your smartphone. They’re under neffyConnect. You’ll see a, you know tab at the top, “neffyConnect”. Under neffyConnect you have all the patient support systems we have. There’s coupon, there’s a coupon for copay assistance. You want to give that to the pharmacist or give the numbers to the pharmacist, and they’ll enter those numbers, and they’ll get the discount down to $25, hopefully. Or if it’s cash pay, you can also go to GoodRx. And if you go to GoodRx, GoodRx has a coupon for $199 cash pay. Now the other alternative is to go to BlinkRx. Now, the way you get to Blink is through neffy.com. And again, either through neffyConnect or there’s a button called “Get neffy Now” that will take you to the section of the website where you can do one of multiple things.
You can ask your doctor to send the prescription to our specialty pharmacy company, BlinkRx, or BlinkRx can go to your doctor and ask for a prescription if you want. Not all doctors pay attention to that electronic system, but, you can call your doctor and say, “I requested a prescription, can you please give a prescription?”
And then the third alternative is that you can get a virtual doctor. So we have we have a system where you can go to a virtual doctor system, where you can get a virtual doctor. If you already have a prescription for auto-injector and you’ve been diagnosed, it’s relatively easy for the virtual doctor to prescribe up neffy, and they would prescribe it.
Now, the advantage of going through that system is the following, is that BlinkRx, our specialty pharmacy company, will check your insurance coverage within minutes so they can get almost instantaneous results on whether you’re covered or not. If you’re not covered, let’s say you’re one of the insurance companies we’re still working with to get on formulary.
Now, once again, that’s a 6 to 12 month process, unfortunately for some insurance companies. Once we’re on formulary for all these insurance companies, it will all be automatic. You won’t have to get prior authorization anymore with neffy. But for the short period of time, until that occurs, if prior authorization is necessary, Blink will do all the work for your doctor.
So we will complete the prior authorization forms. We will send it to your doctor. They just have to sign it electronically and send it to the insurance company. It’s all electronic. And then hopefully we can get you full coverage. If if not, we will also try to get an appeal done through your doctor again, your doctor has to sign it. But what we did is we we basically gave a grant to the American College of Allergy, Asthma and Immunology, to the ACAAI. We gave them a grant to write template letters for us, for these appeals. So we have, letters written by professional allergists that know all the issues, and we could pick the right letter for your situation, send it to your doctor. All your doctor has to do is sign it and send it to the insurance company. And hopefully we can get you the insurance coverage so you can get neffy at the lowest possible price. Again, we always protect you that… and unfortunately, I’ve already seen in the data that some people are paying full price for neffy, which is, you know, $700 or more dollars.
And and we don’t want that. So, please remember that even if you’re uninsured, even if you can’t get your insurance company to cover, you should be going to GoodRx or you should be going to BlinkRx and never paying more than $199. So we don’t want you to pay more than $199. And that’s why we set up the system.
But if you just go to the CVS or go to your local, you know, private pharmacy and you don’t, you don’t remember to go to GoodRx, or you don’t remember to go to BlinkRx and get those coupons, they may charge you a lot more. And we actually don’t want to see that, we’d actually rather try to protect the consumer, patient, caregiver from paying more than they would for their auto-injector. And we really don’t want it to be a barrier. We don’t want cost to be a barrier for you to get neffy if you choose to switch.
Dave: Right. And it really depends on your pharmacist as well, because we have at our pharmacy, I won’t talk about who that is, but at our pharmacy, they will actually sort of automatically look up your prescription with GoodRx and some of the others. But not off. Not all branches of the same pharmacy will do that.
Richard: So no, unfortunately. And there is a financial incentive almost for them not to. So you should be diligent to I mean, a good pharmacist will do that. So you have a good pharmacist, but some will actually charge full price because they actually make more if they charge full price, unfortunately.
So sorry to say. And so that’s, that’s really and I think the insurance companies that they said are relatively positive, we’re hoping to have some good news after New Year’s, about a couple of the major insurance providers, who are very aggressively pursuing getting neffy covered. And we’re working with them to get an agreement quickly.
And they kind of see the value of neffy for their participants, their plan participants. So they’re actually very, very positive about getting coverage quickly. You know, even in that case, it would be only maybe about four months after launch that, that those companies would pick it up. And by the way, to their credit, Anthem, decided to cover at full price even before they negotiate any discounts or contracts with us.
They decided to cover neffy without prior authorization. So if you’re on Anthem, you should just get automatic coverage. They’re not usually one of the companies that do that. They usually have a six month block where they don’t cover any new drug for six months until they can negotiate an agreement with the company. Anthem decided to cover neffy right away.
You know, after their medical review, they decided that it’s in their best interest to cover it immediately.
Dave: That’s great. And I just want to reiterate. So no one should be paying more than $199.
Richard: No. Absolutely not.
Dave: Always get the coupon from GoodRx or from Blink. So, and what I also want to make folks understand is that you worked to price this comparatively with the generic auto-injectors out there.
Richard: Right.
Dave: But because your time to expiration is twice as long, there’s significantly more value there.
Richard: Right. Exactly. And, you know, the fact that it doesn’t have the needle, so it’s safer. I mean, if, for example, if you’re a couple with a child or several children that have this disease and you have a babysitter, or let’s say you have Grandma, Grandpa that take care of the child after school because you’re working.
You may be reluctant to leave an EpiPen with Grandma, Grandpa, or you may be reluctant to leave an EpiPen with the babysitter because you’re afraid that they may accidentally inject themselves, which happens 3500 times a year in this country or more. And they go to the emergency room for that. And you may not be comfortable leaving them with it.
Neffy can’t hurt them. So neffy now becomes something where you can be comfortable leaving. And you, you might want more of them. You might want to have them in different places and position them more so that longer expiry makes that more affordable. Also, where, if you limit yourself because the cost to two EpiPens a year and you got to use one at the school and you got one, mom and dad are sharing, we wanted to make it more affordable for neffy that maybe for the same, let’s say $100 you can get four.
You can get four prescriptions now, and now you can put them in more places and have them easier, more available if needed.
Dave: And the last twice as long.
Richard: Well, right, right. So we wanted to say, if you’re getting two EpiPens a year because of, let’s say, the cost and you’re paying $80 a year, $100 a year for two EpiPens.
And, you know, now you can get for neffys, you know, and we wanted to make sure that it makes your life more convenient and, and the potential to treat somebody, you know, having it in more places, having it available just in case. You know, that’s all part of this, you know, carriage availability, epinephrine doesn’t help if it’s not with you at the time of an event.
So that to us is almost as important as getting rid of the needle. So again, affordability is part of that. So we really tried to think through this and to where we’re still making a good profit. We’re not saying we’re not making a profit, but we want to make sure that it’s not a price barrier for patients and caregivers. And that was really our objective.
Dave: Terrific. Well, I think you’ve answered all of my questions.
Richard: One other comment about BlinkRx is that one thing I forgot to mention. Just so you know, if you do go through BlinkRx now, it doesn’t matter to us if you go to your local pharmacy and get it, or you go to BlinkRx, but Blink or will ship it to your home at no cost.
So it’s a little more convenient. I mean, it’s becoming very, very common nowadays. A lot of different, you know, virtual pharmacies now that ship directly to your home. So if you do go through, blink our X again, we facilitate everything to get you insurance coverage. BlinkRx will never charge you more than $199 because that’s just automatic there.
But then they’ll also ship it to your home and it will come to your house and you’ll have it, you know, within a day or two. So we hope that that’s also just a convenience for patients and caregivers that they can get it online if they want.
Dave: And because of the lesser temperature sensitivity, you don’t have to worry about it sitting on your doorstep for a couple of hours.
Richard: Exactly. Anything else you want to tell our folks, our readers, anything else on your mind?
Richard: No, I think I think we covered everything. Again, we’re working really diligently to get everybody, you know, full insurance coverage, get neffy on the formularies as quickly as possible, because we know that’s a major concern for people. If their insurance company doesn’t cover it, it’s very stressful for patients and caregivers.
And then again, we’re we’re hoping, you know, by late spring you’ll have the one milligram for the smaller kids. And even working on that lower dose for the even kids under 15 kilos. So we’ll, we’ll we’re working really hard to try to address all the needs in the community as quickly as possible.
Dave: Well, thank you so much for your time. Appreciate it. Rich,
Richard: Thanks, Dave. Great. And you do a great job with SnackSafely, so thank you.
