Todd Hobbs Transcript

To see the full interview, click here.

Steve: This is Steve Freed with Diabetes in Control and we are here at the American Diabetes Association 77^th scientific session 2017 and we’re here to present to you some really exciting interviews with some of the top endos from all across the world. And we have the honor of speaking to Dr. Hobbs. Tell us a little bit about yourself and what you do.

Dr. Hobbs: I’m Todd Hobbs. I’m the chief medical officer at Novo Nordisk here in the U.S. I have the opportunity to speak to many different individuals about diabetes every day, and that’s in the form of data, publications, but also talking with the leaders of ADA and other organizations about how our products can help with the care of diabetes patients throughout the U.S. We work with the FDA, so I have a long and broad range of responsibilities. But…it’s centered around a passion for diabetes. I have had type 1 diabetes now nearly 30 years, and I have a son who developed diabetes at age 5, so he’s had that more than half his life. Whether I am working and talking about diabetes, I am living with diabetes every day. So, I think the passions line up pretty well together.

Steve: Do you use a CGM?

Dr. Hobbs: I do use a CGM, yes.

Steve: And your son?

Dr. Hobbs: Absolutely. As a parent, it makes it a whole lot easier going to bed at night not having to worry so much about what’s happening with his sugar.

Steve: I see in the diabetes arena a lot of people that work for [diabetes] companies have diabetes, mostly type 1.

Dr. Hobbs: At Novo Nordisk, we have that as well. Many of our employees are here because of a personal reason. Themselves or their family members have an association with diabetes in some way.

Steve: I’m an avid bike rider. I certainly follow Novo One….

Dr. Hobbs: We had some of the guys at the booth with their bikes. I wanted to take one of the bikes, but they wouldn’t let me have it, but yeah, they’re a pretty amazing group.

Steve: I imagine normally in a bike group, and this is off-label talking (laughter), I imagine people on bikes are not type 1 diabetics; they’re not professional bike riders, so it must be pretty difficult to find those people.

Dr. Hobbs: There’s more than you would think and it’s pretty amazing how we’ll they’re controlled and how the biking itself enables them to take less insulin and really stay fit and make it easier to control their diabetes.

Steve: I’m sure they all have CGMs.

Dr. Hobbs: They do and they have to take in a lot of calories too when they’re racing and training. It’s quite a balance.

Steve: How many presentations, posters and abstracts do you have here?

Dr. Hobbs: It’s one of our largest, 60 total abstracts at the meeting. And probably the largest oral presentation we just finished, which was the DEVOTE results, the cardiovascular outcomes trial for degludec, basal insulin.

Steve: Which are you most proud of?

Dr. Hobbs: I think DEVOTE to be honest, and I can speak to a few others. But DEVOTE was brought to us as a requirement by the FDA when we finished the program for degludec for approval. There was some question whether there was an increased cardiovascular risk in some of the post-hoc analyses and we certainly didn’t believe there was, but we agreed to do the trial. We got it turned around in a matter of months to start and then to have the results now that have closed the question of any increased risk of CV endpoint for degludec is very reassuring. Then also, the benefit of showing that it truly does lower your risk for hypoglycemia versus insulin glargine, that’s something to be proud of for us.

Steve: One of things when I work with patients and I talk about degludec is what’s the difference? How do you explain what degludec does, because it’s a little more complicated than insulin…it’s a little bit more of a unique product. What makes it so unique?

Dr. Hobbs: The way I like to explain it in a less scientifically rigorous terms, If you’ll excuse me, it’s really like pearls on a chain. We call them multihexomers. As degludec is injected it forms these very long, up to 10,000-unit chains of these multihexomers of insulin degludec and the only way that the individual units of insulin can come off and begin to go into circulation is from the ends of these long chains. So, as you’re injecting or titrating or increasing your dose and you worry that maybe you’re going to have too much insulin, it actually acts as a buffer that allows it to continue to slowly fall off the end of these long chains. If a patient moves their dose timing each day by a few hours here or there, it will not effect at all the reproducibility of the effect that you’re going to get from degludec. We know that from the trials that also the from patients as well.

Steve: Can you tell us what the DEVOTE data was all about?

Dr. Hobbs: DEVOTE is the first insulin trial to do this type of large cardiovascular outcomes trial. Based on the 2008 FDA guidance it was set up to rule out an excess risk of cardiovascular harm looking at MACE, which is major adverse cardiac events, as endpoints. All-cause mortality, certainly if someone dies, but also non-fatal stroke and non-fatal MI as well, that was the primary endpoint. It was blinded in a vial versus glargine 10 in degludec. Patients titrated their insulin as they would in a clinical trial based on investigator input. Once we accrued 150 events we actually were able to do an interim analysis with a small group of individuals seeing that. We sent that to the FDA and that was the basis of approval for Tresiba. Once we accrued 633 MACE events the trial was over and that was the results that we showed today. It did confirm that there was neutrality, we met the endpoint for the hazard ratio requirements to show that there was no excess risk and one of the key secondary endpoints was severe hypoglycemia. Episodes requiring the assistance of another and these were adjudicated, meaning that a team of experts looked at those in a blinded fashion, and there was 40% less severe hypoglycemia with degludec versus glargine and 53% less at night, so nocturnal [hypoglycemia] was cut down by over half. So very encouraging.

Steve: What about the data from the DUAL-7?

Dr. Hobbs: The DUAL-7 is our trial where we look at Xultophy, which is our fixed ratio combination of tresiba (degludec) along with victoza. This was just recently launched, our sales team is just now out there talking about this with HCPs and getting coverage on the formulary. This was Xultophy, 1 injection a day only, going against up to 4 shots a day of basal bolus so full-on basal bolus. Patients came in on glargine 20-50 units and they either intensified by switching to Xultophy and titrating if needed or they intensified by adding meal-time insulin with Novolog. The results at the end were very encouraging, both the arms achieved a reduction in A1c, a very nice drop, that was equal, and also the numbers meeting the goals of A1c < 7% or < 6.5% were identical for both arms. What this is telling us is that you can use 1 shot a day of Xultophy and get the same glycemic results as the basal bolus. Another endpoint that adds to that is that you can do that and lower your risk for hypoglycemia with Xultophy vs. basal bolus. Patients also lost a little weight versus gain weight on basal bolus. The biggest endpoint in my mind was that 38% of patients on Xultophy were able to have an A1c < 7%, did not gain any weight and did not have any hypo. To me that’s the strength of the data.

Steve: What about your GLP-1? Are you in the process of doing cardiovascular studies?

Dr. Hobbs: We have several ongoing. Victoza, which is approved, we did the LEADER study, which was at last year’s ADA in New Orleans. We had filed that with the FDA to be added into the label and we have an advisory committee meeting set to discuss that cardiovascular outcomes trial. SUSTAIN-6 is our semaglutide, weekly GLP-1 injection, that is actually filed with the FDA now as well. SUSTAIN-6 is part of that package. We are not asking for a pre-approval claim to say we benefit, but the data did show that there was a reduction in the MACE endpoint and it did have benefits like LEADER did. That data is included in the submission for that drug. Then also we have an oral GLP-1 that is in phase III, and that has the same type of pre-approval cardiovascular outcomes trial. We want to make sure that even though it’s the same semaglutide molecule just in a different delivery via oral route, there could be changes in the way it affects many things, including cardiovascular risk, so the FDA has discussed with is we will do a separate cardiovascular outcomes trial for the oral form of semaglutide.  That’s ongoing.

Steve: You’re actually doing a separate study even though it’s the same drug.

Dr. Hobbs: Exactly. We will see in a year or so when the results are available if that’s enough to satisfy the FDAs concerns or not and I’m sure we’ll be presenting that in a year or two.

Steve: What is the significance of the LEADER trial today?

Dr. Hobbs: It is significant. When you look at the debate over diabetes drugs and initially saying that they should not increase the harm to patients who already have a CV risk. Now to say we have a reduction in CV risk by 13%; all-cause mortality, 15% and we are effectively treating their diabetes with a robust agent, lowering their weight, etc., that is a nice message for Victoza. At this point we can say that we have the only GLP-1 agent that has shown a benefit. There have been a few other agents, both short-acting and weekly, that recently announced that they were neutral. It is rather unique that perhaps it is related to the molecule itself, but liraglutide or Victoza, is the only GLP-1 agent that has shown benefit at this point.

Steve: Novo has been in the business for a while. They have a lot of different drugs. Maybe you can share with us, what’s in the pipeline that is exciting?

Dr. Hobbs: I think we talked about it which is oral semaglutide. That’s probably the most exciting, our weekly injection is going to be here obviously a lot sooner. Hopefully we will have a ruling at the end of the year. That data is very robust, it really will indicate to most everybody that looks at the data, that it is the best GLP-1 data that has been seen. When you talk about the excitement of being able to reproduce that kind of data and take a once-a-day pill, I think that’s exciting. That’s in the relatively manageable 3- to 5-year timeframe. We are still exploring things like a weekly insulin injection or combining a weekly insulin injection with a weekly GLP-, things like that, but that’s further down the pipeline.

Steve: Are you doing anything with smart insulin?

Dr. Hobbs: We are looking at a liver preferred insulin, there are a lot of ways to look at how you would make a smart insulin. It is still very early, but we know that if we can actually have more effects in the intra-hepatic circulation around the liver and less in the periphery, that should cut down on the risk of hypoglycemia and weight increase so that’s how we are going about it, but again it’s still rather early for that one. If we could have an insulin that would only work to get your glucose down to the appropriate level and then stop working that would be the dream, and we are going to continue looking for that.

Steve: I know you’ve got to go, but I have one favorite question. It has nothing to do with Novo… If you could have any HbA1c level what would that number be on that piece of paper?

Dr. Hobbs: 5%