Steve Freed: This is Steve Freed. We’re here at the American Diabetes Association, 77th Scientific Studies and we’re here to present to you some exciting interviews from some of the top endos from all over the world and we have with us a special guest, Dr. Sam Engel. And maybe you can give us a little background on who you are, what you do and why you’re here.
Samuel Engel: Thanks, Steve. Well I’m here because this is obviously a very important meeting for diabetes investigators and researchers. I’m the section head for diabetes at Merck research labs in our late stage development group and we have obviously a wide variety of posters and presentations here related to a number of different efforts that we’re working on.
Steve Freed: Ok so, I notice here that you have a couple of important studies and one of the new SGLT-2’s, that’s an oral. That is kind of unique because everybody else’s is pretty much injectable. No, that’s a GLP-1. I’m sorry. So, the ertugliflozin is a new SGLT-2 that is before the FDA and you had a couple of presentations. What were the results and what were you presenting? The important issues.
Samuel Engel: We have a total of five different presentations here at ADA this year related to ertugliflozin. There are two studies that are being presented for the first time, 26-week data. One is the VERTIS SITA study and the other is the VERTIS MET study, VERTIS is the name of our clinical trial program. VERTIS SITA looked at the co-administration of ertugliflozin and sitagliptin in patients who were not well-controlled on a background of diet and exercise. It’s a complement to a study that we previously presented, VERTIS Factorial, which was also a co-administration but on a background of metformin. In the results of that study, what we saw were very consistent changes from baseline in A1c reduction, about 1.6-1.7% versus 0.4% with placebo, in very similar changes from baseline as what we saw on a background of metformin. The second new data set is VERTIS MET; this is a placebo-controlled study of ertugliflozin in patients on a background of metformin therapy, so second-line therapy. These data, 26 weeks, again showed very similar efficacy responses both in terms of glucose as well as weight and blood pressure as we’ve seen throughout the entire program, about a 0.7 and 0.9% reduction with the two doses of ertugliflozin. VERTIS MET is important for another reason, it’s actually a two-year study, and we’re presenting the six-month data. This is a study that is going to be looking at bone health. We are following bone mineral density in patients in this study and the study is also enriched with a higher proportion of women who are at risk for osteoporosis in this study. So we are presenting at this meeting the six-month data on bone mineral density and we are pleased to see that. you know, in terms of the bone mineral density, we don’t see any adverse impact at that time point with either the 5 or 15 mg doses of ertugliflozin.
Steve Freed: So, in that study, if we kind of just went over some of the things that many physicians would look at is weight, blood pressure, A1c, and lipids. What were the results? What did you find?
Samuel Engel: Ok, so in the VERTIS MET study, A1c reductions were 0.7% and 0.9% for the 5 and 15 mg doses.
Steve Freed: And how did it perform on the secondary points?
Samuel Engel: Ok, so on the secondary end points, in regards to percent of patients at A1c goal as well as the secondary endpoint for weight and blood pressure, we saw very consistent responses with what we’ve seen across the entire program.
Steve Freed: You know every drug in the world has side effects. You couldn’t name a drug except, I wouldn’t call it a drug, but even water has side effects, too much or too little. What about the safety profile and the side effects did you find out in this study?
Samuel Engel: So both in the study as well as across the entire program, of course you know safety is something we need to look at very carefully and tolerability. You know to this point looking at both this study and the entire program, we see a safety and tolerability profile very similar to what’s been seen with other members of the class. There are higher rates of genital mycotic infections of both women and men generally, but other than that the safety profile really hasn’t identified any specific signals or concerns.
Steve Freed: What additional value would you want to provide to physicians as they leave. Do you want them to take some information with them? What would you like to provide?
Samuel Engel: Well, you know when I look at the ertugliflozin clinical development program, you know what we’ve done is really tried to focus on the spectrum of diabetes treatment choices and the studies that we’ve done, many of which are being presented here at ADA, really look at the use of ertugliflozin across the treatment paradigm both as initial therapy, monotherapy, or initial therapy in combination with sitagliptin, second-line therapy on top of metformin, or third-line therapy on top of patients who are on metformin and sitagliptin. That spectrum is very important to understand because clearly patient choices in regards to anti-hyperglycemic medications really need to be individualized or a different context. What I can tell you is that across the spectrum we’ve seen very consistent responses in regards to A1c, blood pressure and weight.
Steve Freed: I presume that in order to get approval you have to do a cardiovascular study. Where are you along those lines?
Samuel Engel: So our cardiovascular outcome study is ongoing, it’s fully enrolled. Last year we had announced that we were doubling the size of the study and so we have completed enrollment of approximately 8,000 subjects in that study. Obviously the study remains blinded but we are looking forward to those results. Currently, it’s projected that the study should end sometime around 4th quarter of 2019. Now it is an event-driven study, so if the event rates are higher or lower than we anticipate, then the study completion date could be affected as well.
Steve Freed: In one of the other studies that reduces burden of hypoglycemia related to DPP-4 inhibitor use, that was an abstract. Was that an oral also?
Samuel Engel: That was a study done by our colleagues at the Merck Center for Observational and Real World Evidence, and there was an analysis that was done looking over the course of the last number of years when DPP-4 inhibitors were available, the rates of hypoglycemia that were seen in patients taking DPP-4 inhibitors compared to patients taking sulfonylureas. What the authors did was they then projected if DPP-4 inhibitors hadn’t been available, what levels of hypoglycemia would have occurred and what would have been the patient burden as well as the cost burden? And it showed about 50% of the hypoglycemia that would have happened in the absence of DPP-4 inhibitors actually didn’t because of the availability of that class.
Steve Freed: What would you like the physicians to walk away from and with what understanding?
Samuel Engel: I think it highlights the importance of therapies for diabetes that don’t cause hypoglycemia. Hypoglycemia is a burden to patients in terms of their daily life, a burden in terms of the economic cost to healthcare system; it’s a burden in regards to the potential relationship of hypoglycemia, especially severe hypoglycemia with more substantial health issues. Even been linked with increased mortality. In that context, studies that continue to highlight the difference in hypoglycemia rates for DPP-4 inhibitors, and this would also hold for SGLT-2 inhibitors, provide the evidence base that clinicians and patients need now that there are so many different choices and classes of anti-hyperglycemic drugs.
Steve Freed: I want to thank you for your time, I found that to be very interesting, and enjoy the rest of your stay here.
Samuel Engel: Thank you very much.