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Dave Vigerust Transcript

May 30, 2017

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Steve Freed: We’re here at the American Association of Clinical Endocrinologists. Maybe you can start off: Tell us a little bit about yourself, what you do, and your background.

David Vigerust: I’m chief scientific officer for a molecular diagnostics company in Nashville, Tennessee. What we do is primarily genetics. We do some clinical chemistry but for the most part genetics and cardiovascular medicine, diabetes, small bit of cancer, but for the most part our focus is in diabetes and cardiovascular medicine.

Steve Freed: When you say the word genetics, all kinds of things come to mind. There’s been some unbelievable changes and the future is obviously genetics. What part does your company play in this?

David Vigerust: We’re in a position to try to provide some guidance to clinicians on some underlying genetic predispositions that you might find in patients. So, for example in the diabetes area, we’re here to present a test that we’ve developed called Haptoglobin. It’s a test that offers some guidance to clinicians about the risk that someone with diabetes might have for cardiovascular events. This is a protein that traditionally has been involved in acute phase reactions so trauma, infection. In the diabetic area, it relates to oxidation reactions that occur in the blood vessel that can lead to an accumulation of oxidized LDL into a plaque, increased inflammation, which can lead to rupture of that plaque. So, for patients that are diabetic that have a particular genotype of haptoglobin, they are at a significantly higher risk of a coronary event, if they have this genotype.

Steve Freed: How does that differ from when we test for cholesterol and your LDL is not proportioned to where it needs to be. You’re at risk. What’s the difference between that risk and the risk for this?

David Vigerust: This is an underlying risk that’s irrespective of whether you’re a healthy active person or whether you have a good diet, or whether you do all those things that you’re supposed to do to keep our health at its peak. There are five or six things that all of us are counseled to do better to make sure that our health is at the highest level. On the genetic level, this is not something that a person did by making poor choices. This is something that they were born with. There are some ways of mitigating that inherent, inborn, innate risk. So, as opposed to an LDL, where you can maybe do something about it, you can take some medicine, you could eat better and exercise more. You can do things to improve your own well-being proactively. This is something that really you can’t do much about, because that’s what you were born with. This particular test doesn’t exist anyplace else in the U.S. and really doesn’t exist clinically in the world. There’s only one other place that does this test and it’s for research purposes only. We’re the only lab that does it by molecular means and the only one that can offer guidance to clinician on what they can do about that. There actually is in this particular case a pharmacogenetic step. There’s a pharmacogenetic process that you could undertake to mitigate the risk that you have from this underlying genetic predisposition.

Steve Freed: When you say mitigate the risk, most of the time a doctor’s going to say you’ve got to increase your physical activity. They’d have to eat better. I’m going to give you a blood pressure pill, I’m going to give you a statin. We do that now already. What is going to help?

David Vigerust: Those are all things that you would continue to do once you knew what the genetic predisposition was. In this particular case, the role of this protein is to capture free hemoglobin, so every second or so we’re processing a couple of million red blood cells, so they are constantly being recycled with fresh ones. The iron that’s contained in that hemoglobin has a highly reactive nature. When it’s free in the tissues, it can interact with LDL, it can interact with other molecules to cause oxidative stress and as a result of that you can have oxidized LDL, you can have an accumulation into the blood vessel, causing more and more inflammation. This is something that you can do something about if you knew what the genotype was. So that’s why we’re here is to try to offer some more insight to clinicians on what can be done in addition to these other steps that are already being implemented, like the statins and the blood pressure meds, and the better diet and the improved exercise.

Steve Freed: Most people, probably 70-75% of the people, are mostly likely going to die from cardiovascular events, from heart attacks, stroke. They don’t die from diabetes. Actually, it should be higher up on the scale when we talk about what people mostly die from. So, someone comes in and who would you perform this test on, because we already know those people that have diabetes, elevated A1Cs, we know they’re at risk from heart attack, we don’t need another test to tell them, hey you’re at risk. Where do you see this?

David Vigerust: This provides the most benefit to patients that have uncontrolled A1Cs. It provides the most benefit to the patients that might be struggling with trying to get their diabetes under control. This particular genotype is represented by almost 40% of the population. So, if you’re looking at just the diabetic population, 40% of those patients are going to have a homozygous copy of this gene. So that means we can dramatically impact 40% of the diabetics. If you have this gene, your increased risk is upwards of 1000%. So, it’s a significantly higher risk for a cardiovascular event if you have this particular genotype. So, our general approach is to test everyone with diabetes and try to get them on the therapy to reduce that risk back down to baseline as soon as possible.

Steve Freed: You said it reduces the risk for people with elevated A1Cs. How does that reduce the risk?

David Vigerust: In this case, the treatment is a simple over-the-counter vitamin E supplement. So, it’s an easy thing to implement. Everyone can afford to do it. It’s freely available at any pharmacy or any regular vitamin shop or supplement store. The important thing is you have to know what the genotype of the patient is.  There have been studies that have been done to show that vitamin E long-term in the general population actually increases the cardiovascular risk, so in this particular case, knowing what the genotype is provides you the avenue to pick the appropriate patients to minimize their cardiovascular risk and not endanger anybody else who may not have this genotype. If you have a 1/1 genotype, your acute phase proteins are operating optimally. They don’t need any extra help. In the case of a 2/2, the structural formation of the protein prevents it from getting into the tissue where it no longer neutralizes the free heme, so in this case the vitamin E serves as a surrogate antioxidant. That allows you to neutralize the iron, prevent it from causing oxidative injury, and prevent it from accumulating in the kidneys, causing kidney damage, and overall reducing the overall risk to the patient.

Steve Freed: What you just said was that this genotype will tell you that number 1, the patients have a risk, number 2 there is a treatment therapy for these particular people and it’s simple vitamin E at a cost of pennies, compared to other things you might want to add. Can we back off the other treatment modalities and just take vitamin E, or this is in addition?

David Vigerust: This is a supplement. This is an additional tool to further reduce the overall risk. It doesn’t take the place of anything else that’s being done to medically manage that patient. It’s just adding an extra tool to provide them as much protection and as much reduction in risk as possible.

Steve Freed: I’ve heard talks in the last couple of years that with the genotype, we are now at a place with science where we can do genotyping and determine that certain treatments will work for these patients and certain treatments will not. Now, using this same type of chemistry, we can actually find the perfect treatment for every single patient by their genotype.

David Vigerust: Our laboratory does that same type of work also. Precision medicine. Pharmacogenetics to make sure that a given prescription is going to be most effective in that patient. Every one of us has slight differences. Polymorphisms that drive the metabolisms of these drugs and if we don’t optimize that. We pair up the medication with the individual patient, we’re not getting as much benefit as we potentially could by the treatments that we’re providing.

Steve Freed: I had a conversation with a company in Great Britain, with a young fellow who actually has a company where he does the genotype and he actually determines, I don’t know if this is possible, he actually determines via your genotype, what type of exercise and what type of foods would be best for you as an individual. I can go out and press 400 lbs. weights. That maybe not be best for my genetic makeup. Maybe I should just be riding a bicycle or whatever the case may be.

David Vigerust: We do that kind of testing as well. I’m familiar with that. There’s ways of looking to see if you’re optimized for fats or optimized for carbohydrates. If you benefit most from aerobic exercise, weight training, or resistance training. There’s quite a lot of information that we can glean from our genetics, which can provide some insight on what would be the best course of therapy, whether it’s exercise or diet or medications. There’s a tremendous amount of information that’s present there that we’re just barely learning how to tap into.

Steve Freed: What about prevention of cancer? Or finding out if you’re at greater risk for certain types of cancer?

David Vigerust: That’s been done, in the case of BRCA1 and BRCA2. That gives you some potential insight as to whether you have an increased risk as a consequence of this gene. There are also genes that are used specifically to target for medications. There’s a number of companies that have drugs that target a specific gene. If you knew that you had a variant in this gene, you would know that this drug would or would not work for you. That’s done quite often in oncology. That’s probably the one place where genetics has had the most adoption is in the area of oncology. They use it extensively to genotype the tumor and genotype the patient.

Steve Freed: We hear all the time about women that get a double mastectomy that don’t have cancer, that are just at risk for cancer. To take major surgery in a major step like that, you really have to believe in the science.

David Vigerust: And, you have to have a good physician that understands the genetics and can give you solid guidance and direction on how much of a risk. Having the gene doesn’t guarantee that you’ll get cancer. Having any gene doesn’t guarantee that you’ll have a particular disease. It may push you down the road. There’s this idea that we require multiple hits. Multiple things have to go wrong in order for a disease process to develop. That’s the case with cancer. Even though you may have one variant or one mutation in a given gene, or oncogene doesn’t guarantee you’ll get cancer, but if other things happen. Environmental exposures or diet or something else happens to you along the way, those push it one step closer to finally developing it to whatever disease process.

Steve Freed: So, it could be that a lot of things have to happen. By using your test, what percentage of risk, can we put a number on it? Say, your risk is up 200%, but these things have to happen?

David Vigerust: In this particular test, there have been well-documented studies that have looked at, what is the attendant risk having this particular genotype. They’ve been done around the world. Different groups have looked at haptoglobin. The difficulty has been, there wasn’t a way of actually testing patients in large scale. Even though you could do it in the lab, you could use all kinds of technical processes that you can do in the lab easily that you can’t do in a clinical practice. So, what we can do is we can offer some additional guidance on this genotype leads to 200% or 300% risk and that’s backed up by clinical studies. Then, if you take the vitamin E supplement, you can reduce it back down to baseline. In this case, you’re probably still looking at a 50% increase over the general population, but you have reduced it significantly. With the other things you are doing to medically manage this patient, if they’re all compliant, if your patients are compliant with what you’re asking them to do, that risk comes down a little bit more and their potential for a long and healthy life is that much more assured.

Steve Freed: It’s not going to tell you how much vitamin E to take.

David Vigerust: Actually, there is. There is an algorithm for that as well. If you are a haptoglobin 2/2, the recommendation is that you take 400 international units. That’s a dosage that you can find over the counter just about anywhere. There has been some evidence, not quite as robust, in patients that only have a single copy, that taking half a dose or 200 units might prove beneficial as well. That is still going through some additional clinical testing. It’s very solid that if you have a double copy, 400 units significantly decreases you risk.

Steve Freed: This is getting off the subject a little bit. There are 3 or 4 types of vitamin E. Is there one in particular that is recommended?

David Vigerust: Well, there are 8 different isoforms of vitamin E. The one that’s most common is the alpha tocopherol. But you can find different isoforms that behave slightly different. Some of them a little bit better than the alpha version, and some of them a bit worse than the alpha version. What you get with a good quality vitamin E supplement is a mixture of different isoforms. That seems to be sufficient to provide the additional protection. What you’re trying to get is the antioxidant effect of the vitamin E.

Steve Freed: So, you walk into a physician’s office for the first time. You want to tell the physician about your test. What do you tell them? To help them get a better understanding of what you do.

David Vigerust: We go through a little bit of the biology to explain how the test works, what the biological activity of this particular protein is normally in a normal patient and then inquire about how they’re treating their patients if they are having difficulty keeping A1Cs low. If they’re seeing a lot of patients that are struggling in being compliant and having their A1Cs low. Then offer this as a potential avenue for them to further reduce the risk in their patients. Once you explain the biology to it, it becomes very intuitive that this is an easy thing to implement. It doesn’t take a lot from the patient’s perspective, it’s not cost prohibitive. If you have a patient that’s compliant and listens to what you suggest to them, you can see some very nice decreases in their overall risk. You can measure this. There are chemistries that you can use to measure inflammatory mediators in the blood vessels. It would give you some indication that it’s working and that the supplementation is improving their overall inflammatory process.

Steve Freed: To determine which patient this would work best for, would you say that it should only be used for diabetics with an A1C of about 6, would you say all Type 2 diabetics, Type 1 diabetics?

David Vigerust: All diabetics can benefit from it. The ones with uncontrolled A1Cs seem to have the strongest benefit because it also helps to improve their A1C levels. It also improves some of the HDL levels as well. There is a bit stronger evidence with those that are uncontrolled, because that’s been the focus group that most of these clinical studies have looked at. Trying to get those most highly at risk back down to a range that’s more manageable.

Steve Freed: You said it improves A1C?

David Vigerust: Some of the studies that have been done clinically do come down some after they’ve been implemented in the treatment.

Steve Freed: Treatment of what?

David Vigerust: Vitamin E, after you’ve done the genotyping. There is that need to do the genotyping. We’ve had physicians ask why don’t I just give everybody vitamin E, it’s easy, I can send someone out to the corner drug store to pick it up. We’re back to that physician’s study that discussed long-term treatment of vitamin E in the general population and there is a risk. So, if you were to do that, you’d be actually increasing some potential risk for some of your patients if they were not a haptoglobin 2/2 genotype.

Steve Freed: Do you have a poster or abstract that is coming out either here or ADA?

David Vigerust: We have a publication that’s coming out this next month in June in clinical diabetes that’s highlighting the overall effectiveness and the utility of haptoglobin. We also have an additional publication out in Future Cardiology that’s also coming this next month that examines haptoglobin in the cardiovascular medicine space.

Steve Freed: So, what other things could you mention? I mentioned exercise and nutrition. And we do that. I mention something you say, we do that too. What do you do besides this test?

David Vigerust: We have a full panel of next-gen sequencing. So, if you were interesting in FH for example. So, since this is an endocrinology meeting, there are a number of physicians who have patients who are suffering from FH. We can look at the three to four genes that are primarily responsible for FH and offer some guidance on whether some of the new medications that are out now, the PCSK9 inhibitors, would be effective for those patients. We do some genetics for cardiomyopathies, so arrhythmia issues, conduction issues, structural issues like aortic aneurism and aortic valve issues. We do some testing for those. We have a clinical chemistry department, we do pharmacogenetics. We’re pretty broad in the sense of genetics. We do some limited oncology, but that space is relatively full and crowded and our niche is in cardiovascular medicine.

Steve Freed: So, if people wanted to get more information, learn more about your tests, or even purchase it. Can they purchase off of the Internet?

David Vigerust: It’s not a direct to consumer test.

Steve Freed: No, I’m talking to doctors.

David Vigerust: Yes, they can come on to our website. There is a questionnaire verifying that they are a provider and they can order directly from us through the website or through…

Steve Freed: And it’s a blood test, so they have to get the blood sample…

David Vigerust: Actually, this is an oral rinse test, so it doesn’t require venipuncture. This is a 30 second oral rinse, non-invasive, anybody can do it. It’s highly stable, so if it’s shipped from one part of the country to the next it doesn’t degrade at all. We have testing in every state in the U.S. except for New York. So, we have a fairly broad footprint. Testing is pretty easy and everything is very transparent and open.

Steve Freed: What’s the website?

David Vigerust:

Steve Freed: Anything you’d like to add?

David Vigerust: I really appreciate the opportunity to come and talk to you and appreciate the chance to come to the meeting.

Steve Freed: I think our readers would be interested in learning more and they can get that information on your website. How long have you been in business?

David Vigerust: Four years now. Fairly young company, especially in the genetics space. We’re growing rapidly and we’re interested in being a primary provider for everyone who’s seeing diabetic cardiovascular patients.

Steve Freed: What about insurance reimbursement?

David Vigerust: Insurance covers a fair bit of genetics. They certainly cover for FH. For this haptoglobin test we’re in discussions right now with Blue Cross and with Medicare for coverage. We have a unique McKesson Z-code so it’s under Moldex, so that means if it’s adopted by Medicare it will be nationwide coverage.

Steve Freed: If a company is going to use one of the new cholesterol drugs that costs up to 12 or 13 hundred dollars a month, I would think that the insurance company would say, you need to take this test.

David Vigerust: In many cases, they have. That is one of the points for which they will approve reimbursement right away. If you have a genetic test that shows that you have a variant in anyone of those four genes, it’s an automatic approval essentially, because there is a clear indication that you could benefit from the drug. Whereas if you’re just treating someone that has coronary disease, that doesn’t rise to the level of approval. It’s a specific drug. It only targets one particular protein. So, you really have to have knowledge that there is an FH phenotype in this patient.

Steve Freed: So, you run the risk if you do the test, then the insurance company if you show you’re positive, they’re going to pay for the drug.

David Vigerust: They will pay for the drug.

Steve Freed: If you show you’re negative, it’s likely they will not pay for it.

David Vigerust: Perhaps they won’t. The biology of that particular drug, it will provide some benefit, but it’s not enough benefit to offset the costs. When you have other options available to further reduce that LDL level.

Steve Freed: I want to thank you for your time.