In part 2 of this Exclusive Interview, Dr. Todd Hobbs talks with Diabetes in Control Publisher Steve Freed during the ADA meeting in San Diego, California, about DEVOTE data and how degludec works.
Dr. Todd Hobbs is Vice President and Chief Medical Officer for Novo Nordisk in North America, where he leads the organization’s focus on the implications of diabetes for the patient, healthcare system, and healthcare professionals. He provides overall medical guidance to Novo Nordisk’s diabetes and obesity-related projects.
Transcript of this video segment:
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.