Role of Interchangeable Biosimilars in the Management of Diabetes
Thomas C. Blevins, MD, ECNU, FACE, FNLA, provides an overview of biosimilars and discusses interchangeability status among biosimilars such as for insulin glargine-yfgn for the management of diabetes.
Diana Isaacs, PharmD, BCPS, BCACP, BC-ADM, CDCES: I want to switch gears and talk about biosimilars. We have insulin glargine-yfgn. The brand name is Semglee. This is the first interchangeable biosimilar approved by the FDA. Tom, I know you have so much expertise in this area. Can you define for our audience what a biosimilar is? Maybe talk through how the FDA approves biosimilars and how these compare with the original reference product.
Thomas C. Blevins, MD, ECNU, FACE, FNLA: Diana, I’d be happy to talk about out that. This is important to understand. Let me throw out a couple definitions. No. 1, a biologic is essentially a pharmaceutical agent created in living cells. That’s what we’re dealing with here. Insulin is a biologic. This is a very complicated process. Making a biologic is not like making a generic statin or a generic other kind of medicine; this is complicated. A biosimilar is a biologic medicine that’s highly similar to the reference biologic with no clinically meaningful or notable or significant differences in terms of the safety, purity, and potency. We’re talking about insulin. We’re talking about glargine. The reference biologic, the reference glargine, will always be the Sanofi Lantus insulin. Anytime somebody wants to do a biosimilar glargine, they’re going to reference to the original, essentially Lantus.
Another point is that a biosimilar is an approved version of a biologic medicine with identical amino acid structure sequencing to the originator, which would again be the reference. The intent is to make it as close as possible in every way to the reference biologic. Biologics are complex; therefore, biosimilars are complex proteins. If you look at a small molecules—things that are generics, that are pills—they’re very different from a biologic. I won’t dwell on that, but the biologics are much larger and complicated. There are quite a few biologics available.
The approval process for a biosimilar requires the person who wants approval of their biosimilar to go to the FDA with data that show that the pharmacokinetic/pharmacodynamic data are very similar. Also, they have to show mitogenicity. They have to look at things that are from the bench to the clinic. Then they need to do large, but not terribly large, studies with people who have type 1 or type 2 diabetes and show that the insulin is highly similar in terms of efficacy, safety, and immunogenicity. Those are the standards set by the FDA. The Semglee [insulin glargine-yfgn] people and the Viatris people had to do that. That’s what Eli Lilly had to do when they got Basaglar [insulin glargine] approved. It had to show that all those things, from the bench to the clinic, were highly similar. Then they get approved if their insulin was highly similar. We can talk more about that in a minute, as far as the studies that were done.
Diana Isaacs, PharmD, BCPS, BCACP, BC-ADM, CDCES: Thanks. That’s so informative and helpful. What exactly is an interchangeable product? Are there any other biosimilars that also have this status of being interchangeable?
Thomas C. Blevins, MD, ECNU, FACE, FNLA: Everyone may be surprised to hear that there was no insulin, until now, approved as an interchangeable insulin. Now Semglee [insulin glargine-yfgn] has that approval. The FDA requires that a company does studies that show that you get the same clinical result as the reference product, with no diminished efficacy, no sign of safety issues, and no sign of difference in immunogenicity. What the FDA requires can change, and this is an evolution. The FDA encourages switching studies. That’s a study where you take people with type 1 or 2 diabetes, and you put 1 group on the reference product—the originator, like Lantus [insulin glargine]—and other people on the biosimilar. Then you treat them for periods like 3 months at a time. Then you switch them to the other side to see if there’s any difference, then you switch them back. The question is, how many switching periods will there be? As long as the safety, efficacy, and all that are highly similar, you have a chance of getting approved. You have to show that to get interchangeability. This is the bottom line, and it’s surprising to everyone I think. Interchangeability has not been approved until now, and I suspect there will be others down the road. This is a big deal. I wanted to talk more about the design. We can in a bit or anytime you’d like about the advantage of having an interchangeable insulin.
Diana Isaacs, PharmD, BCPS, BCACP, BC-ADM, CDCES: I’ll just add that 1 of the big things about interchangeable insulin is it means if a prescription is sent to the pharmacy for insulin glargine or for Lantus [insulin glargine], the pharmacist can change it to Semglee [insulin glargine-yfgn] and not have to contact the prescriber to be able to do that. That’s a big deal, and we’ll definitely talk more about that in a bit.
Transcript Edited for Clarity
