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Steve: This is Steve Freed. We are here at American diabetes association, 77th scientific studies and we are here to present to you some exciting interviews with some of the top endos from all over the world. The name is Thomas Seck, MD and tell us little bit about your self
Dr. Seck: Thank you for having me. I am Thomas Seck. I am head of clinical development and medical affairs for the US organization of Boehringer Ingelheim. I am an endocrinologist by training and in the pharmaceutical industry for about a decade.
Steve: Your company obviously has a relationship with Eli Lilly.
Dr. Seck: Yes we do. There is a diabetes alliance between Boehringer Ingelheim and Eli Lilly covering a number of compounds. It started in 2011 and its really a unique and one-of-a-kind relationship to partner in developing and commercialization of various diabetes products.
Steve: it’s been about 3 years when Empagliflozin came out?
Dr. Seck: Yes
Steve: And it kind of caught everybody by surprise because you discovered something that nobody really ever discussed. We always thought that diabetes is all about blood sugars (that’s because we could do something about blood sugars) and now with this drug we can actually do something about helping people live longer and prevent cardiovascular disease. Since most people with diabetes do not die from diabetes but they die from cardiovascular disease, this was a huge breakthrough.
Dr. Seck: Yes
Steve: Your study basically provided the information, so maybe we can talk a little bit about that. What data regarding Jardiance and the outcome is being presented here?
Dr. Seck: Maybe I can take a step back and add to what you already mentioned. I think the importance of cardiovascular disease in diabetes cannot be underestimated. The likelihood of having cardiovascular disease if you have diabetes is 2 to 4 times higher compared to a person without diabetes. On top of that, two out of three patients die due to cardiovascular disease if you have diabetes. So, it’s a very serious problem: it has impact on your life expectancy, so if you are diagnosed with diabetes at age of 60 and at the same time have established cardiovascular disease, your life expectancy is reduced by 12 years compared to individual without these conditions. So it’s a very serious and important condition. When empiric outcomes published in September of 2015, it’s a European diabetes meeting in Stockholm: I think that was first time we saw diabetes medication that showed benefit in cardiovascular outcome. So this is very large, robust study with over 7,000 patients. All of them had type 2 diabetes and cardiovascular disease. What we observed is called 3-point maze, major adverse cardiovascular accident. That endpoint was reduced by 14% but more importantly, this was entirely driven by a reduction of cardiovascular death by 38%. So at that time and still to this day, I think that this kind of results is really considered landmark in management of diabetes. And really opens up for physicians and patients a new opportunity to manage devastating cardiovascular disease.
Steve: So what are you presenting here?
Dr. Seck: So in terms of what we follow up now, at this ADA meeting, is additional data on Empagliflozin. We have 20 abstracts on Empagliflozin only. We have 8 abstract on analysis of empiric outcomes. I think from my perspective really important data is we showed now that the effect of Empagliflozin compared to standard of care for cardiovascular death, for hospitalization of heart failure, for overall mortality independent of changes in blood pressure, in HbA1C and in blood lipids. We know that Empagliflozin has effects: it’s a glucose-lowering mediation, it lowers HbA1C. the question was, is that effect as well as blood pressure lowering effect that we know this compound has. Is that explaining most of of that reduction in cardiovascular death? And the analysis shows that this is independent of this effect. So it continues to be important to monitor and take care of HbA1C. It continues becomes important to manage your blood pressure and blood lipids. That is key in preventing cardiovascular disease. But you cannot mimic by doing the effect we saw in Empagliflozin in empiric outcome on cardiovascular death.
Steve: What are some of the other benefits that you are presenting?
Dr. Seck: We talked about hospitalization for heart failure. That was also major finding in empiric outcome. There was a 35% reduction in hospitalization for heart failure, which was highly statistically significant and another important aspect is the effect on renal complications. We defined an endpoint that was called worsening of nephropathy, which included increases in albuminuria, doubling of serum creatinine and end-stage renal disease such as dialysis or kidney transplantation. For all these endpoints, there was a clear reduction seen in Empagliflozin compared to placebo. We have an additional analysis here at ADA, that looked at what we call renal function slopes (eGFR slopes): we observed that in first dose, there is reduction in eGFR is what we saw in empiric outcome; small reduction is 2-3 mm/min, but then after the years to come, there is a stabilization of eGFR compared to placebo. That was causing lot of excitement for endocrinologists and also for nephrologists that this compound might have potential benefit on renal function over time.
Steve: And that’s not because of diuretic effect?
Dr. Seck: No, that is not due to diuretic effect. But if you have a diuretic, you clearly have no beneficial effect on renal function. And there is probably much more to Empagliflozin than just being a simple diuretic. It works in a very different way from mechanism perspective and has very different effect within the nephron of the kidney.
Steve: So what other products are you and Lilly presenting here at ADA?
Dr. Seck: We have 33 publications overall at ADA. 20 out of those are related to some extent to Empagliflozin. We have 11 abstracts related to linagliptin, which is a DPP4-inhibitor which does not need dose adjustment (Independent of renal function). And then we have additional abstract on basaglar- insulin glargine product. So that is also something we have as part of the alliance. We have new data here for that product showing comparability between that product and lantus in the element 5 study. For Linagliptin, we can share some of the highlights from those 11 publications as well. I think one important one to consider in the arena of cardiovascular outcome trials (this is dominating theme here at ADA again). We will publish and have a poster for the baseline characteristics for our linagliptin cardiovascular outcome trial. It is called CARMELINA. That is a trial that is really dedicated to assess the effects of linagliptin on cardiovascular outcomes as well as renal outcomes so that makes it a little different from other DPP4 cardiovascular outcome trials we have seen to date.
Steve: The new drugs, the SGLT2 and the heart study, I think you really have to go back if you want to know your success….who do you have to thank for your success? I think you have to go to someone that I am sure you know, Dr Nissan.
Dr. Seck: Yes
Steve: What he tried to do in attempt caused the FDA to say that any new diabetes drugs has to do cardiovascular outcome studies because there is a cost to that and most companies would not do that because no body really knew. So I think we have to go back even though his issues with Avandia were incorrect that we know now but because of him your company has been very successful with this new drug and it’s kind of a breakthrough. I was talking to a physician just half hour ago and I said where is it as far as first line of therapy, second like of therapy…and it already has moved up to the second line of therapy, which is mind boggling when we have so many other alternatives. But its like anything else what good is it and I want to ask you about studies showing amputation possible. That information has just recently come out especially for the toes. I personally think that there is ways to prevent that if the patient is educated. What kind of response or what have you seen there?
Dr. Seck: So let me clarify, the information that came out that was announced by the FDA as a safety communication was for canagliflozin (invokana) but it did see imbalance in the CANVAS program that will result in a black box warning. So that’s related to that one end product. We looked as triggered by these findings, obviously outside of our data, we have a large data of empiric outcomes with high burden of peripheral artery disease and we could not identify imbalance in our data. That has also recently been published in Advances in Therapy available online and you can find these data and there is no difference between placebo and Empagliflozin.
Steve: What about other side effects of Empagliflozin?
Dr. Seck: Well, If you look at our prescribing information, there is a number of warning and precautions that can only be in detail under warning and precaution section. Clearly if you use Empagliflozin in combination with insulin, sulfonylurea it can be associated with hypoglycemia. We have hypovolemia is also a potential side effect. There is also something about diabetes ketoacidosis. You probably have heard about this topic over last couple of years. and I think these are the key warnings and precaution that we have as part of the labeling. I really encourage everybody to go back to labeling to get more information about safety information to make sure we have appropriate patients on Jardiance.
Steve: If you were presenting to the mass audience to the medical professionals involved in diabetes care and you were talking to nurses and pharmacists and dietitians and PCPs, and you are talking about Empagliflozin. What would you say to them?
Dr. Seck: I would say to them that this drug Empagliflozin Jardiance is really a new breakthrough medication. Because for the first time with diabetes medication, we have an associated effect on cardiovascular death. Its not a small effect, it’s a sizable effect: 38%. Which really changes and should change moving forward the way we manage patients with type 2 diabetes in with cardiovascular disease. And in that context, obviously Jardiance has been glucose lowering medication. Now with the indication received by the FDA in December of last year, to reduce the risk of cardiovascular death what you also need to consider beside glucose is cardiovascular risk. I think having that at the forefront of making decisions, especially in population where you have diabetes and established cardiovascular disease, I think it will really change how we think about the disease. Because in a lot of ways, you could argue that this medication provides value independent of glucose reduction. So if you have a patient that you believe is already controlled based on HbA1c levels, but has a high risk of cardiovascular disease if that patient had a stroke or had a MI previously and has type 2 diabetes, there is still the value of reducing the risk for cardiovascular death. That really is a change in mindset on when to use drug such as Jardiance.
Steve: So I know that drug is not inexpensive; its fairly expensive. Have there been studies to show the insurance companies, third party payers, that if we can prevent hospital stay, if we can prevent a heart attack, if we can prevent funeral expenses, there’s a benefit. Any studies been done to show…?
Dr. Seck: Yeah. The value piece is really critically important to Boehringer Ingelheim as well as for Eli Lilly. And pricing and cost for a medication needs to be off set by the value. We believe, in the case of jardiance, this is a very straightforward value for position because the expense of cardiovascular disease and type 2 diabetes are enormous in this country. We are spending more than 20 billion dollar every year to treat cardiovascular complications in patients with type 2 diabetes. Changes in outcomes we have seen in empiric outcomes, this is a very clear value proposition even for payors and you might have heard that we are also engaging in what we call value base contracting around Jadiance because it’s a win/win situation for payors as well as for patients.
Steve: Have you been able to put a number on the cost savings? Percentage or anything?
Dr. Seck: i cannot give you a specific number in cost. AS you know the pricing system in US, is complex. There are lot of things involved so I cannot give you a hard number.
Steve: But you have found significant cost savings?
Dr. Seck: If you have a patient population that has high cardiovascular risk, has established cardiovascular disease, there clearly is a value. I think we have to distinguish clinical value for patient because I think that there is benefit for a patient to be around, be with grandchildren. I think that its something difficult to put a dollar value on it. But there is also value for payors because you do reduce healthcare utilization.
Steve: But for type 2 diabetes, what’s the impact on cardiovascular disease that we are talking about in type 2 diabetes?
Dr. Seck: It has huge implications for patients. I started in very beginning sharing with you the impact on life expectancy. The reduction of 12 years of your life taken away if you are diagnosed with type 2 diabetes and cardiovascular disease at an age 60. I think that’s very tangible for patients. On top of that, we talked about impact on costs. Managing cardiovascular disease is very expensive. That’s another financial piece to it.
Steve: And how is your relationship with Lilly expanding your portfolio? What’s in the pipeline? What’s coming up next?
Dr. Seck: So overall, the alliance was established in 2011, so we are now together for number of years and so far it’s been a very collaborative partnership. I think we are really combining the expertise of two top pharmaceutical companies to really provide value for patients with type 2 diabetes. And I think if you look at the product that we made available over the last 6 years, we have launched 8 products. So I think that’s a clear testament providing all these treatment options for the management of type 2 diabetes how successful and how well this alliance between Boehringer Ingelhem and Eli Lilly is operating.
Steve: So what do you think about putting the pharmaceutical drug we have been talking about in the water?
Dr. Seck: In general, I hope its not a serious statement, but in general I think its important to identify the appropriate patient. Right? And that’s why education is so important. Right? Education to physicians that prescribes the drug to make sure they understand the profile, the benefits and the risks associated with it and that is important for physician. On the other side, I think what’s also important in the space is that we need to start educating patients about it as well. The link between cardiovascular disease and diabetes is very well established for physicians. What we have found in some market research that we have conducted is that the awareness of the connection between diabetes and cardiovascular disease is very poor in patients. And therefore also as an alliance, we took it on to have an unbranded campaign, Called for Your Sweet Heart, to really highlight that connection because I think if patient understand “I am at risk for cardiovascular disease” they will be motivated to actively be engaged in the management of diabetes and to reduce the risk of important and clinically meaningful cardiovascular events.
Steve: Don’t most people with type 2 diabetes, couldn’t you say that they are all at risk for cardiovascular disease if they don’t take care of their cholesterol, their hypertension and all the other things that go with it?
Dr. Seck: Yes, you are absolutely correct. The presence of type 2 diabetes is a cardiovascular risk equivalent. So if you have diabetes even without cardiovascular disease, your risk for having a cardiovascular event is clearly increased. You are absolutely correct.
Steve: Are there any future studies being done for prediabetes?
Dr. Seck: For Empagliflozin?
Dr. Seck: We are looking at data we have available, think about other ways to provide value for patient population that we have currently not covered in our labeling. You might be aware that we have already started studies on heart failure patients. These are studies in patients who have established heart failure and its independent of whether or not they have type 2 diabetes. Or even patients without diabetes, because we believe that mechanism of action will also work in patients without type 2 diabetes. So these studies just started to involve. Its called empiric studies. Its two different studies with 7,000 patients planned to be enrolled. We are very much looking forward to the results of these studies.
Steve: When would the results come out? I know it depends…
Dr. Seck: It’s always estimated when you start the study but the expectation is around 2020 we should see the results for this program.
Steve: I want to thank you for your time. All this is very interesting.
Dr. Seck: You are welcome
Steve: if we go back 50 years, we only had one drug. And then it exploded: 1995 until today.
Dr. Seck: I fully agree with you. We have made tremendous progress in this space to provide more appropriate treatment options for patients.
Steve: One last thing I would like to say is that, every diabetes drug in the instructions it says along with physical activity and nutrition, this drug can be very effective. Have they done any studies showing where people actually were educated intensely and they had better nutrition and had physical activity and took Empagliflozin, compared to people that were not.
Dr. Seck: You know you raise a very important point. I am an endocrinologist and took care of lot of patients with type 2 diabetes and clearly the first step after diagnosis is to really advocate lifestyle changes with exercise and also diet changes. And that is standard of care. It is recommended by the ADA as well. So all the studies we are doing, there is a study related to glucose lowering that our initial phase 3 program were done in the context of patient education. So patients were first educated to really adhere to an approved diet and exercise regimen and then the randomization to the drug occurred.