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Dr. Ronan Power – Insulin innovation: A revolution in the treatment of diabetes

March 17, 2020

Because of the increase in people diagnosed with diabetes and the rise of prices for treatment, there is an urgent need to come up with alternatives to insulin.

The rise of insulin prices over the last decade, plus the cost of pumps and syringes, has made treatment for diabetes more expensive than ever. Will a cost-effective insulin replacement ever exist? Dr. Ronan Power discusses Alltech Life Science's breakthrough in insulin pills for diabetes.

The following is an edited transcript of Tom Martin’s interview with Dr. Ronan Power. Click below to hear the full audio.


Tom:            Insulin prices have more than tripled in the last decade, and because insulin cannot be taken orally, pumps and syringes can add significantly to the cost. The result? This treatment is quickly becoming unaffordable for many diabetics, but insulin therapy is critical for most of them, and there's a search for options. One might have been found.


                     Dr. Ronan Power, vice president of Alltech's Life Sciences division, joins us to talk about something of a revolution in the treatment of diabetes. Thanks for joining us, Dr. Power.


Ronan:          Thank you, Tom.


Tom:            Tell us why, first of all, there is this need. I kind of described it in the introduction, but diabetes is a huge problem in this country, I assume.


Ronan:          Absolutely. It's a huge problem not only in the Western world, but it's becoming more and more of a problem in countries that have, if you like, found affluence in the last two to three decades and are adopting more and more of a Western-style diet and lifestyle. It's becoming a really, really big problem. I think one of the figures I saw most recently was an estimated 360 million sufferers worldwide, but that's only diagnosed cases.


                     Of the subtypes of diabetes, the two main ones, of course, people will be familiar with are Type 1 and Type 2. Type 1 typically hits younger people, and that is a type of diabetes where the cells in the pancreas that produce insulin are destroyed, and that can be an autoimmune-type disease or a reaction to a virus, in some cases. The most prevalent form is Type 2, which used to be called “adult-onset diabetes,” but now, it's creeping downwards in the age group and it's hitting people as young as four years of age — even younger — and that's part of the associated obesity epidemic or pandemic that we see in the world today.


Tom:            We're seeing studies that are projecting that if these rates, these obesity rates, continue at current trends, more than half the population of almost 40 states in the United States will be obese in 2030. What are the implications of failing to stop and reverse that trend?


Ronan:          I think they're absolutely massive — and I would say 50% is a conservative estimate. If you look at the implications of obesity as they relate to diseases like diabetes, there is a condition known as metabolic syndrome that precedes the development of diabetes. This is a condition which is characterized by not just obesity, but high blood pressure, high cholesterol or dyslipidemia. That's abnormal blood profiles, high triglycerides and so on and so forth. That can predispose people to many, many diseases, particularly coronary vascular disease or cardiovascular disease and pulmonary disease. That's even before you hit any diabetes threshold. Once people develop diabetes, there's a whole range of attendant problems that come with that, as people are aware of, but one of the larger problems, in my opinion, is the state of insulin resistance that begins to develop in people who tend to be overweight or have a higher-than-normal body mass.


                     Insulin resistance in itself can cause huge problems. Let me just mention an example. One of them is called PCOS, or polycystic ovary or ovarian syndrome. That's becoming a huge problem in the female population in terms of reduced fertility, inability to conceive and inability to sustain a pregnancy. That's a direct implication of insulin resistance. So, we're not just talking diabetes here; we're talking much broader, more debilitating conditions of life, if you will.


Tom:            We're here to talk about something that you're working on, which is an alternative to insulin that you have in development now. Can you tell us about this?


Ronan:          Sure. This is, I guess, the culmination of about 12 years of work in our labs here at Alltech. This started off as a plant-based or a botanical-based compound we found which was able to increase energy production in cells, or seemingly increase energy production in cells. Actually, it turned out to be that it improved energy consumption. So we've been studying this for quite some time, and we actually have made a lot of variance of this particular compound. We isolated it. We synthesized it. We made variations on a theme, as it were. Today, we have a compound, which we call Compound 43 — obviously a very imaginative name, the number 43, the variation of the compound which we developed. So, Compound 43 has got a very unique ability in being able to bind to insulin receptors and activate that receptor in the absence of insulin.


                     In effect, if you want to view the action of insulin on a cell as a lock and key mechanism, imagine that insulin is the key. It fits into a lock, which we shall call the insulin receptor. When both lock and key are working correctly and the mechanism is turned appropriately, that opens a glucose channel and allows glucose to enter the cell and be used properly.


Tom:            Let me make sure I understand up to this point. The compound that you're working on replaces that key.


Ronan:          It replaces the key. It can activate the lock even when the lock is broken, because in Type 1 diabetes, you're missing the key. In Type 2, there's something wrong with the lock mechanism; it doesn't work properly, or not at all, in some cases. But what this compound does is it binds to the insulin receptor (i.e., the lock) and can open it.


Tom:            So, it's doing the work of the insulin.


Ronan:          It's doing the work of the insulin. What we have, in effect, is an insulin replacement. It doesn't bind to the insulin receptor in the same place as insulin. It binds at different locations. Its purpose, simply, or what it does, is it brings the two arms of the insulin receptor together, and once they join together, it activates the insulin cascade inside the cell, which then allows that glucose door to open and allow glucose in.


Now, it's not a runaway reaction, by any means. It does stop, so there is a finite half-life of this compound, which we've determined to be about eight to ten hours. It doesn't crash the blood glucose. It takes it down, but it doesn't bottom it out at a dangerous level.


Tom:            Now, as I understand it, this would be administered orally as opposed to a shot.


Ronan:          Absolutely. This is our big breakthrough in the last year. When we initially tested this compound, we were using it in the traditional insulin-type way, of a subcutaneous injection, or even an IP, an intraperitoneal injection, but we've now developed a formulation which can be taken orally in tablet form, pill form, which works very well indeed. We have actually tested that in mouse models of diabetes, several different mouse models of diabetes, and it works perfectly well. The compound itself, we've also tested in human cell lines — liver, skeletal muscle, all of the major organs that are impacted by diabetes — and find that it works beautifully.


                     It can even be used in concert with insulin, in some cases, because when I describe the Type 1 and Type 2 diabetes, especially for Type 2, there are various levels of it. For some people, insulin works, but not as well as it does in the normal case. That's what we term “insulin resistance.” Insulin resistance can be a graded or a gradated type of resistance. That's why some diabetics, Type 2 diabetics, still take insulin, but this can actually help insulin action, so it works in concert with insulin, in some cases. Because it doesn't share the same binding site, it can be an additive or synergistic effect.


Tom:            I'm sure that anybody who is suffering from diabetes and hears this is going to be quite excited and quite hopeful.


Ronan:          Yes.


Tom:            How should they temper that hope? How far off are you, do you believe, from going to market with this?


Ronan:          First of all, I wouldn't be sitting here if I didn't believe this was a breakthrough. I believe that we can get this out through what we call a phase-one clinical trial in humans within about three years. If it shows promise there, we hope to go right ahead and follow with phase two or three. Best-case scenario, Tom: we're probably looking at six years to market, but I think that's a fast track. That will be a fast track, but I'm hopeful that when we approach FDA with this, they may, in fact, look upon it and say, “Okay.” This type of compound is not unknown, so it has a pretty good historical safety profile.


I believe that there is an urgent need to come up with alternatives to insulin. For whatever reason, Tom, there is some egregious price gouging going on in that market, and people are dying as a result, and I'm not being overdramatic in saying that. You can look at the press, the news, a whole variety of states, and see that people are actually rationing their insulin, using less-effective forms. People have to decide between groceries and insulin, and in some cases, it costs people more than their monthly mortgage, so it's a desperate situation for something that was sold — the patent for this — a lot of people aren't aware that the patent for insulin was sold in 1923 to the University of Toronto for the princely sum of CAN$3.


Tom:            And I understand, now, that a vial of insulin can be manufactured for about $7.


Ronan:          Yes, it is, depending on the grade and the type. It can vary from a very low price like that up to — I'm not sure of the final cost, but certainly, I would guess, no more than $20 or $30, but it's selling for people without insurance — I hear horror stories of people paying $400 to $500 a vial for the material, and that's something that, when you open it, you have to refrigerate it, and it's active for 28 days. What we're looking at is a tablet or a pill, and it's stable for two to three years.


Tom:            I believe I heard you say that a dose, let's put it that way, would last eight hours or so.


Ronan:          Yes.


Tom:             So, theoretically, a person could take two of these pills a day and maintain —


Ronan:          Yes. It will vary per individual.


Dr. Ronan Power spoke at ONE: The Alltech Ideas Conference (ONE). Click here to learn about ONE and how you can access innovation on demand.