Freed: This is Steve Freed with Diabetes in Control and we are here in San Diego for the American Diabetes Association 77th Scientific Sessions and we have some really great interviews with some of the top endos all across the globe. We have a very special guest with us. This is Dr. Jim McDermott who is also presenting. Why don’t we start off with you telling us a little bit about yourself or your practice?
McDermott: Yes, so I am actually a PhD – I work for AstraZeneca, I am head of the metabolics medical affairs team within the US business.
Freed: What do you do here?
McDermott: I am here because we are extremely proud of the presentations and abstracts that AstraZeneca will be presenting throughout the week. We have 51 presentations at this meeting so we are very proud in terms of how we are showing up in science and being scientific leaders in the space of diabetes.
Freed: Which is the 36th one out of those?
McDermott: Oh, I can tell you the top four. (Laughs)
Freed: Can you tell us the new CVD-REAL world evidence study analysis that are being presented from your company this week?
McDermott: Yes, happy to do so. So CVD-REAL is a large outcomes trial that was presented at ACC. The study had over 300,000 patients and we saw roughly 50 percent reduction in hospitalization for heart failure and all-cause mortality for the SGLT-2 class when it was compared to other oral agents for diabetes. So now what we have done is some additional analyses which we are presenting here at ADA. The first is when we’re looking at dapagliflozin, Farxiga, specifically, and again, looking at that compared to the DPP-4 class. Again, it just reconfirms what we saw with the overall class, the SGLT-2 class. What we are seeing is Farxiga resulted in a significant reduction in hospitalization for heart failure, significant reduction [in] hospitalization for kidney disease as well as a reduction in all-cause mortality, and that was compared against the DPP-4 class.
Freed: So out of everything that you are presenting here, you have to have a favorite one or a couple of favorites that you’re really proud of?
McDermott: Yes, I think there are several that I am really proud of. I think one that is extremely timely is the pool safety data. As you probably know there’s been a lot of questions about the safety profile of SGLT-2s, and so last year we actually did analysis where we looked at 30 clinical trials and we pulled the safety data. What was interesting there was that we did not see any sort of imbalance with amputations, we did not see any sort of imbalance with bone fractures and really low incidence of DKA, so it really reconfirms our belief in the overall safety profile of Farxiga.
Freed: What about amputations? We are hearing that people that have poor circulation are losing their toes or their feet.
McDermott: Right. So in our safety pool analysis, what we saw in over 9,000 patients treated with Farxiga, we had eight amputations reported. In the control group we had 4,000 patients treated with placebo; we saw seven patients with amputations. So you’re looking at a rate, if you look at the patient per thousand years, that’s 1.0 for Farxiga vs. 1.7 for the control group placebo group. So bottom-line, we are not seeing any amputations and we do not believe that is a class effect.
Freed: What about kidney issues? Have you seen a reduction in renal failures?
McDermott: We have not seen a reduction in renal failures. In fact what we’re doing is we have a program that we called DapaCare – it’s a large clinical trial program. We believe that Dapa has the potential to show benefit on chronic kidney disease so we are doing a study both in patients with diabetes and patients without diabetes who have chronic kidney disease, and we are going to be looking at the efficacy and results of that work.
Freed: What about a reduction in A1C?
McDermott: We are seeing great reduction in A1C. What we have seen is up to one percent reduction in A1C with Farxiga alone, great weight loss, and blood pressure reduction of 5 millimeters of mercury.
Freed: So with all these benefits, you live longer, your blood pressure goes down, your blood sugars go down and it helps to protect – at least what we’ve seen – the kidney. When are we going to put it in the water supply?
McDermott: Well, I’m not sure it belongs in the water supply. I think it does provide a new option for physicians as well as patients because as you know it’s not just about controlling blood sugar, right? These patients have multiple comorbidities so many of them struggle with weight control, many of them struggle with blood pressure control, etc. I think there are many good agents out there, but I think an SGLT-2 like Farxiga offers a lot of clinical benefits for those types of patients that need more than just A1C reduction.
Freed: I don’t know if you remember the troglitazone drug? It was pulled off the market for liver failure. To this day I am not sure if it was the drug. I think it was found that the doctors were not providing the right liver test to find out which patients would be suitable. But that put a scare in to the medical community as far as writing prescriptions for new drugs. So what would you tell the PCP to make him feel more comfortable with this drug because it’s only been available for a couple of years?
McDermott: Right. I think I would show them the efficacy, because I think it’s a story, right? What’s the benefit-risk of the product? So you want to talk about the efficacy. And again, I mentioned the great A1C reduction, blood pressure reduction, weight loss, and then you also need to tell them about some of the common side effects seen across class such as genital infections, urinary tract infections, and slight risk of hypotension. I think it’s really about educating physicians on the benefit-risk and it’s not just SGLT-2. it’s across the treatment portfolio that they have an opportunity to use.
Freed: Well you are presenting a lot of information. Obviously you are presenting information on Bydureon, a GLP-1. What kind of information are you presenting on that particular as far as the efficacy and side effects?
McDermott: Yeah so we had a great study that we are presenting and we’re very proud of – it’s called DURATION-8 and it’s actually a combination of Bydureon and Farxiga together as initial combination therapy. Since we do have Farxiga, an SGLT-2, and Bydureon, a GLP-1; we’ve gotten a lot of questions from physicians about the possibility of using those in combination and at that time we really didn’t have a lot of data. So what we did is a randomized control trial looking at the combination vs. the individual components. Here at ADA, it’s really exciting because we’re showing a 1-year results and what you’re seeing is sustainability out to a year. So you’re having that A1C reduction, very significant with the combination, great blood pressure reduction and weight loss, and all three of those are sustained over a 1-year period.
Freed: So maybe you can share with us some of the results from the DURATION-8 study?
McDermott: Yes happy to do so, in fact I have the numbers right here.
Freed: What were the drugs that we were looking at?
McDermott: So Duration8 was a combination of Bydureon and dapagliflozin. It’s initial combination therapy compared to the mono component, so it’d be compared to dapa[gliflozin] alone or Bydureon alone. So what we saw there was really some nice A1C reduction with the combination as well as weight loss and blood pressure reduction.
Freed: Can you share some of those numbers with us?
McDermott: Yes I would be happy to do so. I have the data right here.
Freed: Yes, that would be great.
McDermott: If you look at the A1C reduction we’re seeing a 1.75 with the combination vs. a 1.4 for the exenatide alone versus the 1.2 for Farxiga alone. So, you can see it’s not completely additive but it is a significant difference compared to the mono components.
Freed: Let me ask you a question: If someone has an A1C of 11 or an A1C of 7, the drop in A1C is not going to be the same. It’s not going to be the same; you can’t just say one number. So in looking at those numbers what was the average starting A1C?
McDermott: So in the Duration8 the average A1C at baseline was 9.3 across the three groups.
Freed: What were the other baselines?
McDermott: In terms of body weight, we’re looking at body weight in terms of kilograms. Pretty much it was 90-91kg across the three groups. Systolic blood pressure was across the three groups, again, the systolic was about 130.
Freed: GFR in those?
McDermott: As you know, Farxiga has a limitation in terms of its use with regards to EGRD. So in these patients, the baseline data, they had roughly a 95 EGRF.
Freed: So that is a huge drop in A1C.
McDermott: It really is actually.
Freed: You can actually put a dollar value on that. I guess that is how they price it. I think if you drop an A1C one point, you’re going to save thousands of dollars on a yearly basis; over a lifetime, it is very significant. I guess that’s one of the reasons why some of the drugs are so expensive. So what else is there in that particular study? It’s very interesting because I mean you have two drugs that are very powerful and they work very effectively together.
McDermott: So if I can share with you a little bit about what we saw too in some of the other efficacy parameters. So with weight, we saw a 3.3 reduction (kilograms) in the combined group versus a 1.5 reduction for an Exenatide, and then a 2.3 reduction for dapa[gliflozin]. So again, it’s not an additive but you do see a nice effect. Can I tell you a little bit about blood pressure?
Freed: Yes, please.
McDermott: So again, with the systolic blood pressure, we saw a 4.5 reduction in systolic blood pressure compared to a 3 millimeter reduction for exenatide, versus a 2.4 reduction for Farxiga.
Freed: And what about the side effects?
McDermott: Side effects as you would expect, we did not see any hypoglycemia, actually, which is very nice because both with the SGLT-2 and the GLP-1, you really see no hypoglycemia. That is really one of the true benefits or attributes of these two compounds. So, you’re getting great A1C reduction, but there is no risk of hypoglycemia.
Freed: For the patients that were put into the study, how many were there? And were they on other drugs or insulin?
McDermott: So within the study we briefly had 230 patients per arm and they were on metformin as background medication.
Freed: Newly diagnosed? It wasn’t prediabetes, it was newly diagnosed? Obviously for a person on metformin, I would not consider them long-term diabetics.
McDermott: They were not newly diagnosed. They were on metformin. If they were on other medications they would have been washed out but they would be on a stable dose of metformin. And you’re looking at patient with a very high A1C of 9.
Freed: Do you know what the response was for patients?
McDermott: No I do not. In terms of how they felt? No I do not. I can tell you I was involved in Farxiga in terms of the early development and it was interesting because if you talk to some of the study coordinators many patients could identify if they were on drug or placebo because they could experience weight loss, they could experience blood pressure reduction if they measure their blood pressure. What I’ve heard is patients are really satisfied with this medication because again limited side effects and great A1C reduction, weight loss, and blood pressure reduction.
Freed: How long was this study?
McDermott: This was a 52-week study but it is going to continue on for another year.
Freed: That was my next question: if you lower A1C, you lower blood pressure, you lose weight and then all the sudden you say we’re taking the drug away, that would cause havoc. So they’re running it for another year?
McDermott: That is correct. We believe that you see the stability because many drugs, their effects wane over time. With this combination we saw the results at 28 weeks and now at 52 weeks and the 52 weeks are very similar to what we saw at 28 weeks and we believe we’re going to see similar control after three years.
Freed: So this would be a very ideal drug for people with an A1C that is certainly around nine and below. Anything higher I would think that insulin would be the first thing that most physicians would give. But now it’s another option. If we go back to 1950, we had one drug and insulin. It took us 50 years to develop one drug. Now, 1995 to today, if you count the number of combinations including insulin in a triple or quadruple therapy, we’re talking in the millions of possible combinations
McDermott: And I think that is great for physicians and patients because then they can find the right medication that gives them benefit with low risk of side effects.
Freed: Well it was easy in 1950… if you had type 2 diabetes there was no decision, you were just put on sulfonylurea. Today, it difficult. It’s better, no question. But it is more difficult for the physician to take that multiple drug combination and to see which one is going to work best because everybody’s different. Now they’re working on gene therapy where eventually, by doing some DNA and once we know your DNA, we’ll know what drug is going to be suitable for you and that will take the decision away and will make the physicians’ job much easier.
McDermott: Well it will definitely make the decision easier.
Freed: As of today, I think it makes it a little bit more difficult with all these options available. But we’re seeing a drop totally across the country or across the globe of A1C, so we’re learning that it takes time. So maybe you can talk a little bit to us about DapaCare – AstraZeneca’s new clinical program.
McDermott: Yes, DAPACARE is a term that we use, it’s an umbrella over our clinical program with Farxiga, dapagliflozin. This is a program where we have several studies, DECLARE our CV outcomes trial as part of DapaCare. We also have a CKD study looking at Farxiga in patients with chronic kidney disease and this is both patients with diabetes and patients who do not have diabetes. We also have, within the DapaCare, a large study that we just kicked off for heart failure. And again, what we’re looking at is patients with diabetes, and we are also including people without diabetes, but with heart failure.
Freed: I don’t know if you mentioned the risk for death reduction for the SGLT-2 Farxiga and also for the combination…are there numbers for that?
McDermott: No, not at this time. As I mentioned, we have DECLARE, which is the largest outcomes trial with the SGLT-2 class. We have over 17.000 patients in that study. We expect that to read out next year. What’s unique about that study compared to some of the other cardiovascular outcomes trials is we have patients with established cardiovascular disease and then we also have patients without established cardiovascular disease but they have risk factors. So I think it’s a broader population than what we’re currently seeing in these clinic needs and these cardiovascular outcomes trials right now.
Freed: And when will that end?
McDermott: That will be finishing up in 2018.
Freed: Ok, so next year it should finish?
Freed: Will you be announcing that at next year’s ADA?
McDermott: Well, I can’t commit to whether we’re announcing it at ADA or EASD but as soon as we have the data available, we’re going to be very excited to share that.
Freed: Well it’s always exciting to find a company that is at the forefront of diabetes care because they certainly need every bit of help they can get. So I applaud you for what you do.
McDermott: Well, thank you very much.