Peter L. Salgo, MD: Now we’ve got to look into the future, because if I hear everybody correctly, and I think I do, biosimilars are where we’re going. There’s a certain number of reference drugs, and now the biosimilars are beginning to...I don’t want to use the word “invade,” but they’re beginning to be a part of the market and are less expensive with similar efficacy (if not identical efficacy). How do you raise clinician awareness about these biosimilars and about the safety and efficacy of the medications? Where do we start on that, Vibeke?
Vibeke Strand, MD: I think programs such as what we’re talking about, right now, are the way to help clinicians become not only aware of but comfortable with biosimilarity and the fact that these have been characterized in far more detail (including through a clinical trial), that they’re really not generics. They actually have some benefits because, being reverse engineered, they’re also benefiting from the much better manufacturing processes that we have now.
Peter L. Salgo, MD: So, we can take drugs that were approved in the bad old days, despite all of the deficiencies, and work and make them cleaner and better. I don’t mean cleaner as in more sterile, but in a more efficient way.
Vibeke Strand, MD: Well, they’ve already been made cleaner and better, but also, we can make the biosimilars cleaner and better.
Allan Gibofsky, MD: One of the things we do in the American College of Rheumatology each year is we identify 1 topic and we have what’s called the Great Debate about it. And this year, the Great Debate consists of 2 of our senior clinicians talking about the pros and cons of biosimilars. I think that’s going to really heighten clinical awareness in our physician community.
Peter L. Salgo, MD: But a debate implies that somebody is going to be in favor of them and somebody is not going to like them. Is that really the way that’s going to go?
Allan Gibofsky, MD: Probably not (knowing these 2 individuals), but I think it is going to be an opportunity to lay out, as we’ve done in the course of this presentation, all of the problems, the benefits, the risks, and the efficacy and safety, and put it out there for all to see. And, ultimately, clinicians will heighten their awareness and then have the information to make the informed decision.
Gary R. Lichtenstein, MD: The moderator will chime in, and the moderator has a very important role, in any aspect of anything, to really put the pros and the cons together, if you would.
Peter L. Salgo, MD: We’ve got what, about 50 biosimilars? That’s a large number—50 biosimilars in the pipeline right now for various products that have been submitted to the FDA (Food and Drug Administration) for review for whatever the states decide. This number of products in the pipeline clearly has to affect planning considerations going forward.
Vibeke Strand, MD: I think it does. Basically, there are at least 50 that are under review. And so, we’re looking across oncology, gastroenterology, rheumatology, and dermatology, and we have to realize biosimilars are here to stay. I think that has to make a difference in the marketplace.
Peter L. Salgo, MD: Are you guys sitting down saying there are 50 products out there and that we better plan now for when they hit the market?
Cole Wilson, PharmD: There’s a certain element of planning, always. You want to be prepared, but you also want to wait until those drugs come to fruition, because there are many things that can happen. We already see a lot of legislation now that is delaying some products that are coming to market. So, you want to be thinking ahead, but you don’t want to think too far ahead when you’re doing your planning. Let them come out and then make those decisions.
Vibeke Strand, MD: Legislation or patent fights? I think it is litigation.
Cole Wilson, PharmD: Litigation, sorry.
Peter L. Salgo, MD: In what regard?
Allan Gibofsky, MD: Well, there’s a built-in period of time after which there is an approval—after which and during which the patent holders scour to see if there’s been patent infringement. And the biosimilar manufacturers look to see if the claims of the originators are indeed patentable or obvious. So, this is the lawyer’s full employment act when it comes to getting biosimilars to market.
Peter L. Salgo, MD: I was going to say, listening to the words “litigation” and “patent,” that’s part of the reason that these things are not as cheap as they might be. There’s a lot of legal cost built in here, but still, 50 biosimilars is a lot of biosimilars.
Cole Wilson, PharmD: It is.
Peter L. Salgo, MD: Given that not all of them are going to hit the market, enough of them probably should. There’s going to be price competition here. How do you play that from a plan’s perspective?
Cole Wilson, PharmD: Absolutely. It’s always the front-runners that are going to run and pave the way for those that come behind it when the precedent is set. But, again, in the biosimilar market, each product is unique. The best way I’ve ever heard it explained is [that] each one is a snowflake. When you look at them, they’re very similar, but the actual structure of them is very unique. So, we’re going to have to look at each one individually.
Peter L. Salgo, MD: Wait. They’re all unique. They’re all snowflakes. They’re all different, but the package insert is identical.
Cole Wilson, PharmD: Well, yes. And to your eye, when you see a snowflake outside, they all look very similar.
Gary R. Lichtenstein, MD: So, it depends what zoom lens you use.
Cole Wilson, PharmD: That’s right.
Gary R. Lichtenstein, MD: And that’s really the key thing.
Peter L. Salgo, MD: Tell me about it.
Gary R. Lichtenstein, MD: If you look from a reasonable distance and say, “This is clinically relevant distance,” that’s what makes the difference.
Peter L. Salgo, MD: That was your point?
Allan Gibofsky, MD: Yes.
Peter L. Salgo, MD: The meatball effect: “This works. Give it.”
Allan Gibofsky, MD: We have an analogy. There are who knows how many nonsteroidals, and they all have similar, if not identical, package inserts. They’re looked at as a class, and what you hear the nonsteroidal manufacturers say is, “Let’s make another one, because even if we only are able to get 1% of the market share, that covers our cost and makes a profit.” So, I’m not surprised that there are 50. I’m not surprised that there may be 100 someday, because you only need a small percentage of the market to justify your existence.
Gary R. Lichtenstein, MD: It’s very important to look. The FDA has a very important role to look at these 50-plus agents directly, because, for example, in looking at erythropoietin when that came about, a small change in a rubber stopper, for example, led to pure red cell aplasia. So, the manufacturing processes have to be looked at with extreme scrutiny.
Peter L. Salgo, MD: But, again, I would assume that’s what’s going on.
Vibeke Strand, MD: Oh, yes, definitely. As a matter of fact, before you can even do your trials with a biosimilar, you have to have already had the manufacturing plant inspected, and you have to already have your final manufacturing process established. The fact that there are 50 of these under review, or more than 50 of these under review, by the FDA means that they already have been manufactured successfully.
Allan Gibofsky, MD: The FDA is probably one of the few agencies where, when they come and say, “I’m from the FDA and I’m here to help you,” you can really take that as a good thing, as opposed to some of the other agencies.
Peter L. Salgo, MD: Are you going to have an auction? Seriously. Are you going to say, “OK, we have 50 biosimilars in this class and this class and this class, let’s go”? The reverse auction, though—not the most expensive, the least expensive.
Cole Wilson, PharmD: From healthcare’s perspective, again, we have a pharmacy and therapeutics committee. It’s composed of physicians. We have pharmacists that present the data. They present the clinical evidence. Part of what we include in that presentation is cost, and then our physicians have a vote on those things that will go onto our formulary. So, again, as each unique agent comes out, I think we need to evaluate each of those. A presentation needs to be made with each of those, and we will make decisions based on that data of what’s best for our patients.
Peter L. Salgo, MD: Let’s say that you make that decision, and you’ve got a biosimilar right there in your managed care pharmacy formulary, and it’s got a preferred status. “We like this drug. It works great, patients like it, and some of them are asleep.” And now, a second biosimilar becomes available for the same reference biologic product. Now, where’s the challenge?
Cole Wilson, PharmD: I think you go through the same process. It’s certainly a challenge because, now, you’re doing a complete review again. What are the timelines of when these products come out? Is it annually? Is it every 6 months?
Peter L. Salgo, MD: There are 50 of them.
Cole Wilson, PharmD: Yes, absolutely.
Peter L. Salgo, MD: It sounds like they’re coming out every 38 seconds.
Cole Wilson, PharmD: Right, and so it’s going to be a lot of resources and time that we put into reviewing those. But to do what’s right—I think that’s the process that we have to follow.
Peter L. Salgo, MD: Does that differ from the review process for generics?
Cole Wilson, PharmD: Absolutely.
Peter L. Salgo, MD: How so? Why?
Cole Wilson, PharmD: With generics, we know the bioequivalence, so we know it’s a lot easier to show product A as exactly the same as product B. There isn’t the small variation, so once a generic is only formulary…
Vibeke Strand, MD: The difference is the regulatory process. I mean, my goodness, there are already 10 guidance documents written by the FDA around biosimilars, and they promise at least 4 more.
Peter L. Salgo, MD: I guess where I was going with that, though, is not in the preapproval process—not the FDA. But these are approved now. So, all that work has been done. Now they come to you. Is the approval process to get this on the formulary, or knock off a favorite status drug now that the FDA has approved another biosimilar? Is that just cost?
Cole Wilson, PharmD: I think it’s more than cost. Again, it’s the same thing that we’ve talked about here—the continuing themes. It’s the patient success. It’s, again, the availability of the product and how it’s supplied. It’s all these different factors. It’s more than cost. All those will be a factor of cost, but even patient success and how they do, if they’re a failure on a product simply because it’s a lower cost, in the end, that’s going to be more cost for that patient and more cost for the healthcare system.
Peter L. Salgo, MD: But I thought the FDA said they’re not going to fail?
Gary R. Lichtenstein, MD: The issue is, they’re going to be tested in rheumatoid arthritis and other diseases, and not necessarily the diseases we treat. And that’s where the difficulty lies in making that clinical decision. So, there will be investigator-initiated studies that come about, and those will help to at least get a look into things. And, if there’s a signal, that will go back to the FDA. The FDA will then investigate further, but they’re not going to have standard registries.
Peter L. Salgo, MD: That’s what we were talking about before. Now, this issue becomes interesting. If you’re going to make the pivot from what it’s approved for to something else, then they haven’t looked at the bioequivalence in that, and you’re going to look at that instead.
Vibeke Strand, MD: For instance, I think that it’s already obvious with the infliximab biosimilar that first came out in Europe, that there have been studies like this. There have been postmarketing studies. There’s registry data. We’ve already seen what’s been published in terms of NOR-SWITCH and the DANBIO registry. We are going to get that kind of information.
Now, how many biosimilars come out—as to how much we’ll get more data on each of them—is going to be a big question. But I think people will also become a lot more confident about the whole regulatory process for a biosimilar—sufficient to say, “This product is going to behave like the reference product.”