Mutasem Rawas-Qalaji, B. Pharm., Ph.D., the director for the Center for Drug Discovery and Development and an associate professor at the Department of Pharmaceutical Sciences in the Nova Southeastern University College of Pharmacy, talks about his groundbreaking experimental pre-clinical trial that hopes to reduce the need for epinephrine injections when one is suffering from an allergic food reaction.
Interview conducted by Ivanhoe Broadcast News in December 2016.
Food allergies are life threatening allergies, how common is it in the United States for people to have these allergies?
Dr. Rawas-Qalaji: Historically, there wasn’t a lot of data, but right now I think we have some good data that’s being published by the allergy organizations. Recently, the Journal of Allergy and Clinical Immunology, one of the leading journals in the field of allergy, published an article which discussed the numbers for almost 12 years. It showed that allergies due to food are actually increasing as are hospitalizations due to food allergies. The research also found that approximately three percent of all children might be at risk of fatal anaphylactic reactions due to food allergies.
This is a serious issue, isn’t it?
Dr. Rawas-Qalaji: It’s a big problem; since the incidence is increasing and most of the time allergic reactions don‘t happen in the hospital but when you are in restaurants, at the park or on a trip.
Exactly, because you could come in contact with something you’re highly allergic to, which is of course is why so many schools have banned peanuts.
Dr. Rawas-Qalaji: Exactly, and I think what makes it even more complex is that these children, and even adults, don’t know that there are any peanut-related products in the food that they’re eating. Often, they are exposed to the food that they’re allergic to or eat it without even knowing.
We know and many of us have heard obviously of the Epi-Pen®, because that is the main tool, weapon so to speak, to fight this kind of life threatening allergic reaction. Can you say about how many people are armed with an Epi-Pen? Who needs to have it on them? I guess tell us how that works.
Dr. Rawas-Qalaji: There is a great consensus between the allergy organizations (worldwide) that the first line of treatment should be epinephrine. Patients that are experiencing allergic reactions should immediately inject or administer epinephrine. The only way to get this life-saving medicine right now, especially if you are outside the hospital, is to use an auto-injector. Until now, it seemed that not too many patients carried the auto injectors with them all the time. Today, people are much more aware about the seriousness of allergic reactions—or anaphylaxis–since they can lead to fatalities if not treated immediately in the most severe cases.
Tell us how the Epi-Pen® works since this is the first line of treatment today.
Dr. Rawas-Qalaji: If patients start to experience an allergic reaction, they either inject themselves – or caregivers or parents are supposed to inject the children – with the auto injector. Basically, you need to take it out of the pack and inject it. At the same time, I think that the difficulty is that, most of the time, to inject yourself or even inject someone who is dear to you is not so easy. It requires a lot of courage and a lot of training to do the injection. The key is also to not withdraw the injection right away; you should maintain it in place to allow the drug to be transferred from the injection into the muscles, i.e. the area that is being injected. You need to maintain it in the location for about 10 seconds to ensure that the entire dose is actually delivered into the muscle.
Where do you inject the medicine?
Dr. Rawas-Qalaji: Into the thigh muscle.
And then hold it?
Dr. Rawas-Qalaji: Hold it for at least 10 seconds. It’s very challenging. The auto-injectors are very effective if used properly; they deliver the dose and they save a lot of lives, but the fact is that, first of all, it’s an injection. There is always an anxiety associated with the use of injections. Second, they are bulky, so you have to carry them. You have to make sure that you have enough space for them where ever you are, and most of the time you need (i.e. to carry) more than one injection, for every place you are going to be. Another issue is that they come in fixed doses of only 0.15 mg for children and another dose of 0.3 mg for adults. We know that the children vary in size and weight and for ideal effectiveness the dose should be tailored according to their weight, but this is not the case. You end up in many cases either over dosing or under dosing the child using one of the only two forms available.
There’s one last thing that I really want to highlight – the stability issue. We know that patients have to actually replace auto-injectors almost on a yearly basis because they don’t have a long shelf life. The cost associated with replacing them almost every year or year and a half adds another burden on the patients or their parents.
That’s an important point, too, because if it’s expiring you have to replace it. Let’s be honest, this type of medication isn’t inexpensive, is it?
Dr. Rawas-Qalaji: With the recent price increases, it is often really difficult for patients to buy these auto-injectors.
Now the question is, is there a better way?
Dr. Rawas-Qalaji: Well, this is what we’ve been exploring for some time. We’re trying to come up with a different way to administer the drug – one that can be more convenient and more user-friendly to the patients. It does not require a lot of training, and it does not involve any fear, so it is less invasive than the injection. We came up with a way to administer the drug using a tablet that easily dissolves under the patient’s tongue. This tablet (design) was based on our pre-clinical studies and we are hoping it will deliver the same amount of drug (in humans), at the same time that the injection does.
How long have you and your team been working on this?
Dr. Rawas-Qalaji: We started in 2010 here at Nova Southeastern University when we began the optimization of using nanocrystal and microcrystal technology to enhance drug delivery.
What was your reason for even wanting to do something like this in the first place?
Dr. Rawas-Qalaji: Honestly, at the beginning I was doing my basic studies (PhD). I was working on this project. I had the opportunity to work with real pioneer experts and researchers in this field. I worked with my supervisor Dr. Keith Simons; he is a well-known scientist in the pharmacokinetics area, but also my co-mentor, Dr. F. Estelle Simons. She is a well-known pediatric allergist and she has a specific interest in the area of anaphylaxis. She has a-lot of publications in this area and they always wanted to have the benefit of being able to deliver the drug in a different way. This is where I started working on the tablet idea.
I developed the tablet so that it would actually break down very quickly, in a matter of seconds, in 10 seconds, with a really small volume of saliva. Once they break down, the drug gets absorbed from the sublingual mucosa. Working with those pioneer scientists actually gave me the interest to pursue it (i.e. development of alternative delivery method) and then, as a result, I started interacting with actual patients because they are everywhere; they are your neighbors, they are the parents of your children’s friends and so on. I started to hear from them and to what extent this is actually impacting their life. I became passionate about the project because I feel that I am actually doing something to serve the public — to be able to employ my education, my training and my experience to develop something that would benefit the patients in a significant way. I can touch the hearts of these parents that are always living with the fear that something might happen to their children.
Tell us how does this pill work and compare it to the injector as far as risks and benefits.
Dr. Rawas-Qalaji: The way the injection works is by injecting the drug in a solution format using the auto-injectors. Then, the drug solution is deposited in the muscle area and is absorbed from the blood vessels that supply the muscle into the systemic circulation. For the tablet, the design is called oral disintegrating tablets. Usually these tablets are to be placed over the tongue to be swallowed to be absorbed into the gastrointestinal tract. However, the tablets I’ve designed are oral tablets, but for sublingual drug administration, meaning they go under the tongue. There’s a big difference when you try to characterize these tablets and when you formulate them. It (i.e. orally disintegrating sublingual tablet) requires more stringent characteristics. Once you place these tablets under the tongue, they should disintegrate within 10-15 seconds maximum and release the drug where it is processed. Once one of the tablets touches a very minimum amount of saliva, it dissolves. That way, we ensure that the maximum amount of drug, if not all of it, is going to get dissolved immediately after the tablet breaks down. Then the blood vessels from the sublingual area pick up the epinephrine and it is dispersed through the systemic circulation, making it available exactly the same as with the injection.
It’s the same medication?
Dr. Rawas-Qalaji: Well, it’s not going to be the same strength because the absorption from the muscles after injecting the drug is different than the absorption from sublingual area. Definitely, the amount is not going to be the same. However, we are using nanocrystals/microcrystals technology, where we are able to reduce it (i.e. the required dose). Initially, we had a certain dose to start with, but after applying these technologies, we were able to reduce the dose by 50 percent compared to the initial formulation. We think that this dose should be equivalent to the same dose in the auto-injectors.
You were also explaining the benefits of the pill over the injector, as far as if you make a mistake; the chance of error.
Dr. Rawas-Qalaji: We want to make sure that we’re offering something to the patient that’s more convenient and more beneficial. First of all, these tablets are much smaller than the auto-injectors. Second, you can actually take them wherever you go. You can put them in your pocket; leave them in your office, or even in your neighbor’s house or in the school. They are really small, much smaller compared to the auto-injectors. They are also more stable than the auto-injectors; the tablets’ shelf-life should be far longer than the auto-injectors. You don’t have to actually replace them every year, and at the same time, they’re hard enough so you’re not worried that they are going to break.
Since the concept of putting a tablet under the tongue is not a new development for the patient, they don’t need any special training. It’s going to be easy to explain to the patient how to place the tablet under the tongue. For any reason, if you’ve already injected the drug in your system, it’s already there; you cannot withdraw it or take it back. With the tablet, you can simply spit it out from under your tongue before it fully dissolves and this would stop any further absorption of the drug.
Where are you in your research?
Dr. Rawas-Qalaji: Because we’re doing research in an academic environment, we can only do so much to advance the product development. We already completed all the preclinical testing required to give us confidence that this tablet is ready to go to the next phase. We met with the FDA to try to discuss the project and we are planning a Phase II study with the company that licensed the product. When the right time comes, they should be able to start these types of studies.
Are there any negative side effects?
Dr. Rawas-Qalaji: Based on our preclinical studies, we did not see any serious side effects from these tablets that would make us reluctant to advance the project to the next phase. However, one of the areas that we need to look at very carefully during the Phase II study is not only the efficacy of the drug, but we also need to ensure the safety of the drug. We want to make sure that we’re producing a product that’s safe and effective at the same time.
Any idea when you would start human trials and possibly when a drug like this might be available?
Dr. Rawas-Qalaji: If it was up to me, I would like it to start tomorrow. But, as you might think, there are a lot of studies and preparations that need to be done before we actually start giving these pills to humans. Everything should be set in a way that meets the FDA expectations and standards. The study should be well designed to make sure that we are actually collecting useful information and we can convey it back to the FDA. There’s no specific time on when it’s going to start, but I’m hoping we may be able to initiate these kinds of studies in the next few years.
And that’s for the human trial?
Dr. Rawas-Qalaji: This is for human trials, yes.
Maybe not seeing it going to market for another …
Dr. Rawas-Qalaji: It’s very difficult to decide when it’s actually going to go to the market, because again, there are multiple steps beyond my control that need to be taken. Drug approvals take time. We need to make sure that everything meets FDA expectations and requirements. I’m always hoping that this (i.e. FDA approval) would happen the same year of Nova Southeastern University’s Vision 2020. I’m hoping that this is one contribution that I can give back to the university in a way to show my acknowledgement for their support all through these years.
What do we call the pill, is there a name for it?
Dr. Rawas-Qalaji: Right now, there’s no specific or brand name for it so I would just want to keep it as epinephrine tablet.
Do you feel that this offers patients an important option?
Dr. Rawas-Qalaji: That is exactly my goal. I want to make sure that the administration of not only epinephrine medication, but any medication, becomes more user friendly for the patient.
END OF INTERVIEW
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