Peter L. Salgo, MD: What I really want to do now is make this little pivot. The original drug and, presumably, the biosimilar were approved for use in specific disease states, but we know that you guys, for example, are using some biologic drugs on diseases for which the original drug was not necessarily designed or intended. So, what about using the biosimilars for those same applications?
Gary R. Lichtenstein, MD: If the molecule is very similar, then the regulatory agency and the US FDA have allowed interchangeability, if you would, for the specific areas that were approved initially for the originator. That’s something that has to go through a process. For example, the initial FDA approval for Remicade was Crohn’s. It’s used for rheumatoid arthritis, as well. These are things that have been interchangeable as a consequence.
Allan Gibofsky, MD: Well, let’s be careful. We’re using 2 terms interchangeably.
Vibeke Strand, MD: Right, which we don’t want to do.
Allan Gibofsky, MD: We were talking about interchangeability. I think what we mean is extrapolation—where the biosimilar, having been approved in 1 indication, is allowed to be used in virtually all other indications that the originator is marketed for. Now, interchangeability is a very different concept entirely.
Vibeke Strand, MD: Right. The extrapolation has been interesting because, by and large, the trials that have been done, maybe 1 or possibly 2 clinical trials, [were] usually done in diseases where we have really well-performing outcome measures, and they can best differentiate and have best differentiated active-from-placebo with the reference products.
So, the majority of the trials, at least with the TNF [tumor necrosis factor] inhibitors, have been in either psoriasis or rheumatoid arthritis. In part, that’s because the Crohn’s disease and ulcerative colitis end points are not as “well behaved.” So, the extrapolation is from a relatively different set of diseases to ones where there may be a little bit more variability because of the protein-losing enteropathy. But we’ve actually understood that the mechanism of action across all these diseases is highly similar. And thus, if you can prove efficacy and highly similar behavior, clinically, in one, you should be able to extrapolate to the others. I think one of the concerns is that the FDA has made it very clear that the label for a biosimilar is identical to the label for the reference product (with the exception of the strange name, which is a formal name with a randomly generated 4-letter suffix). That’s going to make it very hard for people to try to figure out how to report pharmacovigilance.
Peter L. Salgo, MD: Why would they make it hard if what they’re doing is they’re adding? Let’s be very clear. What is this little 4-letter doodah that comes at the end of a biosimilar, which wasn’t at the end of the original?
Gary R. Lichtenstein, MD: I’ll go through that for you, Peter. So, for example, Remicade is infliximab-hjmt now. We have Inflectra, which was approved in April 2016, and that’s infliximab-dyyb. Then we have Renflexis, approved April 2017, which is infliximab-abda. And then, Amjevita, in September 2016, which is atto.
Vibeke Strand, MD: How are we going to remember these?
Peter L. Salgo, MD: We’re not. Can everybody just look over here? He’s got it written down over there. He’s cheating.
Gary R. Lichtenstein, MD: I wrote them down so I could remember. But the issue is, this is for safety.
Peter L. Salgo, MD: How so? How does that make it safer?
Gary R. Lichtenstein, MD: If there’s a safety issue that comes up with a particular drug, this will be registered that it was administered, and then one can go back to that group. Say, for example, there is some untoward event that comes about. You can then see which agent the patient had by going back.
Peter L. Salgo, MD: By looking at the suffix?
Gary R. Lichtenstein, MD: And by looking up that directly. So, that’s the way that it helps tracking of this.
Allan Gibofsky, MD: That’s often going to be distal to us, because we’re going to write a prescription for infliximab, and we may not always know what the 4-letter suffix is that the patient is getting.
Vibeke Strand, MD: Or we may not even know which infliximab the patient is going to get.
Gary R. Lichtenstein, MD: But that’s not the key. The key is, you need a way to track things, and that’s the important issue if there is a safety signal that comes about. I would a little bit disagree with your take on the Crohn’s and ulcerative colitis. I think, if you look at this from the standpoint of inflammatory bowel disease, they’re more expensive trials, and it’s much easier to measure by taking an x-ray and getting a Sharp score (or whatever is deemed to be appropriate) than it is to do a colonoscopy, endoscopy, etcetera. And they’re much cheaper trials to run. I think that’s been a big factor in what’s done, and I, rather, would guess that we’re not going to see many, if any, done with inflammatory bowel disease.
Allan Gibofsky, MD: But, Peter, to your point, when you prescribe aspirin, you don’t know if the patient is getting Bayer or St. Joseph’s or Costco or Walmart. You know that they’re getting aspirin, but you don’t know what brand they’re getting. Similarly, we have a way of tracking which brand of infliximab the patient may be getting from the last 4 letters or the suffix. But, at the time that we’re writing for it, we may not know what’s actually being received.
Peter L. Salgo, MD: You don’t have to write for those 4 letters?
Allan Gibofsky, MD: No.
Vibeke Strand, MD: No.
Peter L. Salgo, MD: If somebody knows somewhere in the pharmacy…
Vibeke Strand, MD: The pharmacy and the insurance company.
Peter L. Salgo, MD: Right. At the point of dispensing or at the point of paying, somebody is recording which of these biosimilars, if not the original drug, was actually administered.
Gary R. Lichtenstein, MD: And the variation could be 80% to 120% or so, as a standard within the small molecules. And the same occurs for the biosimilars.
Peter L. Salgo, MD: What does that mean—the variability could be 80% to 120%?
Gary R. Lichtenstein, MD: If you’re prescribing 40 mg of prednisone, they may get as low as 80% of that to as high as 120%, based on a generic product. That’s the current standard within the FDA.
Peter L. Salgo, MD: Right. How does that apply to the biosimilars?
Gary R. Lichtenstein, MD: The same occurs with the biosimilars.
Vibeke Strand, MD: That’s actually a worldwide standard.
Gary R. Lichtenstein, MD: Right. It’s an international standard that is with all products that are manufactured.
Allan Gibofsky, MD: I’d be interested in hearing Cole’s experience in tracking the use of a biosimilar agent, now that we have both the originator’s name and the biosimilar’s name.
Cole Wilson, PharmD: Sure. I think a lot of it is dependent upon when you look at the continuum of care. Exactly as you stated, you might get a prescribed product, and you’re going to write that biosimilar out there, but you don’t necessarily know what’s going to be dispensed in the hospital (in the acute care setting) versus what’s going to be dispensed in the ambulatory setting. So, there’s that mix of product, and it kind of helps muddy the waters.
Peter L. Salgo, MD: We’re going to get into this later, but I want to just ask this right now because this was a big issue several years ago. If you wrote for the trade name drug, the original drug, there was a little checkbox: “Can we administer the generic?” Is that happening here with the biosimilars?
Cole Wilson, PharmD: In today’s market. For the products that are out there, there are 28 states right now that allow for interchangeability. But the standard that exists for the generic products (that have been around for a while) is not the same standard that exists for biosimilars. And even the interchangeability access that you have in some states has nuances.
Peter L. Salgo, MD: We’re going to get to all of that.
Vibeke Strand, MD: Interchangeability is different. It’s another level of regulatory approval.
Peter L. Salgo, MD: Right. But I guess what I’m asking is, if you write for this generic (and I don’t mean the generic drug, I mean the generic name without that little suffix), they can give any of these, and they’re just going to track it back, and they’ll keep taking notes?