Results of INSTRIDE Studies for Diabetes Management

Diana Isaacs, PharmD, BCPS, BCACP, BC-ADM, CDCES: I’d love to hear about these clinical studies that were done to support that Semglee [insulin glargine-yfgn] can be interchanged with the reference product.

Thomas C. Blevins, MD, ECNU, FACE, FNLA: I’m going to ask the audience a question. Diana, you said earlier this insulin is called glargine-yfgn, and that’s Semglee [insulin glargine-yfgn]. So I’m going to ask the audience, what does YFGN mean? What does it stand for? I’m going to go ahead and answer. It means nothing—4 lowercase letters and any biosimilar now just has to have a dash from the reference. Instead of glargine-yfgn, you could choose, zzzz or something.

You’re right. Remember, you have to study these biosimilars in humans with diabetes. There’s an INSTRIDE 1, guess what, that’s type 1; INSTRIDE 2, for type 2; and INSTRIDE 3, which is the study that helps get the interchangeability. I’ll talk about each 1. Let me just give you a brief. In INSTRIDE 1, there were 558 people with type 1 diabetes. This is a study in which 1 group is going to be put on reference—the originator—and 1 is going to be put on the biosimilar. They’re going to be followed for a period of time—24, 52 weeks. As it turns out, the different end points are going to be looked at at those times. They’re going to be looked at for [hemoglobin] A1C changes, hypoglycemia. We’ll talk about it in a minute. In INSTRIDE 2, there were 560 people with type 2 diabetes. These are people who need basal insulin. The reference is compared with the biosimilar. We’ll talk about the INSTRIDE 3 separately.

Let’s talk about INSTRIDE 1. It turns out that if you look at the A1C data—I wish I could show it to you, but I’ll summarize it—they’re the same. There was no difference between the start and finish of the study and between the 2 groups, Lantus [insulin glargine] and biosimilar insulin glargine. We’re talking about -yfgn insulin. The A1Cs were the same from start to finish in this group of people with type 1 diabetes. If you look at the fasting plasma glucose, it’s the same. There’s no significant difference, and that goes for the A1C. The bottom line is noninferiority in A1C results. The doses of the insulin were similar. The A1C results were close to the same. As I mentioned, the fasting glucose, incidence of adverse events, serious adverse events are all very similar. Incidence of hypoglycemia is also similar. No clinically meaningful differences between treatment groups. That’s the type 1 study.

The type 2 study can summarize easily too if you look at the A1C changes at week 12 and 24, between the 2 insulins. It’s very close—no significance there, and no significant difference. If you look at safety—and the same thing goes for serious adverse events, hypoglycemia—if you look at the glargine dose over time, it’s very similar in terms of dosing over time. There are no significant differences. There are no clinically significant or meaningful differences between the 2. There were immunogenicity studies—the INSTRIDE 1 and INSTRIDE 2 studies—looking at antidrug antibodies studies—antibodies to insulin. Does 1 type of insulin cause more antibody production than another? That’s a big deal in terms of safety. The answer is, long story short, the INSTRIDE 1 and INSTRIDE 2 studies over the time period looked at—we have 50-week data in the type 1 study and 24-week data in type 2 and no significant cross-reactive, antidrug antibody presence between the 2—were very similar. Those are the data on the core studies.

INSTRIDE 3 is the switching study. The way this study worked is that people were taken from the INSTRIDE 1 study and were offered to continue into this switch study. One group is left on references in glargine throughout the study, and we’re looking at 36 weeks. Another group is given the biosimilar for 12 weeks, then given the reference insulin for 12 weeks, then given the biosimilar for 12 weeks. It’s a switch study, and their results are looked at. The results again showed that there was no significant difference between the treatment groups when it came to A1C during the different treatment periods. There was no difference in fasting glucose and monitor glucose, and immunogenicity looked very similar too. Those data show us that we can have the confidence, and the FDA has the confidence, that a pharmacist can change without us saying it’s OK because we have an insulin extremely similar in every way that we talked about. That’s a big deal.

Diana Isaacs, PharmD, BCPS, BCACP, BC-ADM, CDCES: Thank you. That was such a good summary of the different studies. That should be reassuring that the clinical outcomes are almost the same between the 2 products, and it should give people peace of mind that if they’re switching between insulins, they can expect the same clinical effect.

Transcript Edited for Clarity