Formulary Considerations for Biosimilars

Peter L. Salgo, MD: What are the key factors that determine whether a given biosimilar is going to show up in some health plan’s formulary, going forward?

Cole Wilson, PharmD: I think we’ve alluded to a number of them already, but first, we’re always going to look and evaluate the clinical and scientific data behind these. We also want to look and see, again, if it is appropriate use for us. What is our access? And what I mean by access is, what is the access on the inpatient side, and what is the access as we move these patients to the ambulatory side (to make sure we don’t have this mix back and forth)? And then, again, it’s cost. We had spoken to that previously. It muddies the waters when we start talking about rebates and some of the other factors that can drive the overall costs down for those who are purchasing the products.

Peter L. Salgo, MD: I guess if you really take rebates out of this and just take a look at the cost of the drug, and whether or not it’s getting put into a given formulary, how do you evaluate this? Do you look at its effectiveness overall? Do you look at its effectiveness for an individual patient versus the reference drug? What do you say to some doctor who calls up and says, “I’ve got a sleeping baby. I don’t want to wake my patient up. The patient’s doing great”?

Cole Wilson, PharmD: Right. That’s a fair argument, and I think those are things that we have to consider when making those formulary decisions.

Peter L. Salgo, MD: How do you ensure appropriate access to these drugs?

Cole Wilson, PharmD: A lot of this has to do with partnerships with the manufacturers. Specialty drugs often have limited access, so there are patients on the acute side for whom we might have access to that product. But then, once they move over in that continuum to the ambulatory side, we no longer have access to that product, and they’re being sent to a third-party pharmacy that has limited access (limited distribution) to that product. This, then, limits our ability to continue to take care of those patients, which is a larger gap for us.

Peter L. Salgo, MD: That makes sense. That being said, you’ve got real challenges. You’ve got a lot of these drugs. These drugs are not inexpensive. And you’ve got a rabid howling group of physicians, all of whom want to get that drug and only that drug, and want it right now. So, what are your challenges, as you see it, as a payer?

Cole Wilson, PharmD: Obviously, you have passion for your patients, and you have passion for what those providers are doing. But we also have to be fiscally responsible in the funds that we’re spending, because we all have a responsibility in lowering those overall healthcare costs that are essentially passed on to that patient.

Peter L. Salgo, MD: I think you mentioned that there was, in Europe at least, a diminution of expectation—that maybe we don’t have to have everybody do just quite so well and we’ll save money in the long run. Did you actually say that?

Allan Gibofsky, MD: No.

Peter L. Salgo, MD: Somebody did.

Gary R. Lichtenstein, MD: I alluded to that. But I think, for example, if you look at the UK, they’re more likely to do a colectomy for someone with severe colitis. It’s cost savings, and it’s less costly than treating with a biologic. This is something where they look at the overall total cost. I think the individual providers are not the ones that are thinking of that, but it’s generally something that we recognize. So, when reviewing studies from different countries, we have to look at the standards within each country and recognize there may be differences, and the approach is different.

Peter L. Salgo, MD: They’re going to say, “This is an expensive disease to treat. It affects your colon. Take the colon out. We’re done.” People don’t like their colons being taken out.

Gary R. Lichtenstein, MD: I’ve had patients come from the UK for other opinions. This is what they were told, and we’ve salvaged colectomy in severe colitis. It is something that’s real. It’s not a commonplace thing where we see patients coming over because of the decrease in the cost, but those that have financial means might do so.

Peter L. Salgo, MD: Let’s bring it back to the United States. You started to nibble on another issue—which I find personally confusing in terms of biologics—which is state-by-state approval. In other words, I always thought we get a drug, we go to the FDA (Food and Drug Administration), the whole nation likes it, and then we’re off to the races. Maybe we have to argue about cost, but at least we know, from the central authority, this is a drug that we’re going to use.

Vibeke Strand, MD: Well, this is getting very theoretical because, first of all, even though we have a guidance document that defines how the FDA would agree to regulate a product and say that it’s now interchangeable (which means that there has to be a multiple switch study, clinical trial, and at least several switches between the biosimilar and the reference product), if that product does get approved as interchangeable, several states—in fact, the majority of states in the US now have passed legislation saying that even if it is considered to be interchangeable by the US FDA—will decide on a state-by-state basis whether or not this product can be interchanged, or substituted, for the reference product (without the knowledge of the healthcare provider).

Peter L. Salgo, MD: Is this something new? Describe this in terms of the introduction of generic drugs. Did this happen with generics?

Vibeke Strand, MD: No. With generics, basically, all the substitution occurs whether you like it or not. You can check the little box on your prescription pad to say “Please do not substitute.” But then, when the patient sees the price between the generic and the patented product, they’re going to agree to the generic. I think this kind of thing is still going to be passed on in a similar fashion. Whether we have the legislation or whether we even have a biosimilar designated as interchangeable, it’s highly likely the biosimilar is going to be used, period—regardless of all this legislation. I don’t know that any biosimilar manufacturer wants to go through the trouble of doing a multiple switch study to get the interchangeability designation.

Allan Gibofsky, MD: In practical terms, Peter, I can prescribe whatever I want, but the insurance company will pay for whatever they want. And in between, there is the creative tension. So, I’m being told, “We’re not interfering with your choice.” And by interfering with what is being paid for, well, maybe they are. It becomes the patient’s issue of what they want to take.

Peter L. Salgo, MD: But that’s a well-known pressure point.

Allan Gibofsky, MD: And it’s the same thing now.

Peter L. Salgo, MD: Yes. But in the middle of all this—and this is what I found fascinating—as opposed to the national policy, there are individual states making individual decisions. And if they’re looking for a way to get me to sympathize with you, you just found it. How do you deal with all of that bureaucracy?

Cole Wilson, PharmD: Again, it’s a state-by-state basis. Each state has its own laws and regulation. If you take a look at traditional products, all states either require or allow substitution of a product (because of the bioequivalence that exists for that and the data that exist for that). I don’t think biosimilars quite have the same case to allow legislation on a standard or national level to require pharmacies to dispense that product. And thus, you’re going to have these discrepancies.

Vibeke Strand, MD: Well, we do know who was behind many of the legislatures’ decisions here, and that was the manufacturers of the reference products—the originators. They really started all of this.

Peter L. Salgo, MD: You’re implying some strange intent. In what regard? They don’t want people to switch?

Vibeke Strand, MD: They don’t want people to switch, and they think that, maybe, the legislation that goes against interchangeability (without the knowledge of the healthcare provider) is the way to say, “Well, this is a better way for you to be able to ensure quality of care.”

Peter L. Salgo, MD: If this new drug is a biosimilar, and it’s been certified by the FDA as similar, how did the states find the leverage to do other things?

Gary R. Lichtenstein, MD: It doesn’t seem right to me that it’s left to a state-by-state decision.

Vibeke Strand, MD: Right.

Peter L. Salgo, MD: So, I’m not alone in this?

Gary R. Lichtenstein, MD: I think it would be more appropriate for the federal government to really say, “Here is the standard. This is what’s done and finished.”

Vibeke Strand, MD: And that’s the way it should be.

Gary R. Lichtenstein, MD: It should be that way, as opposed to individually letting each state decide, because they perhaps don’t have the complete knowledge of all the information, whereas if the FDA is involved with the federal government, they have the knowledge. They have the data. They have the trials that have been submitted. And not everything that’s submitted is public knowledge, so they learn a lot.

Peter L. Salgo, MD: How do physicians deal with this proactively? How do you go about doing the best for your patient, state by state, if you will, and getting what you, as a clinician, think is in your patient’s best interest?

Allan Gibofsky, MD: Peter, would you be surprised to learn that, by and large, the states that have enacted biologic laws for substitution are those in which large manufacturers are headquartered?

Peter L. Salgo, MD: Now that I see you looking at a map, I wouldn’t be surprised at all.

Vibeke Strand, MD: Yes, I think I brought that point up, right?

Allan Gibofsky, MD: To Vibeke’s point.

Peter L. Salgo, MD: But, again, what do you do? This is the political reality, here.

Vibeke Strand, MD: I don’t think it’s really going to change anything very much, because I think that the underlying issue here is cost. And the underlying issue is cost to the patient. The patient is going to do what works out best for them, which is usually what their managed care organization or the insurance company tells them to do.

Peter L. Salgo, MD: The patient is going to do what the patient is going to do, which is, really (if I kept the subtext here, since they’re biosimilar), what the money says to do. Fair enough?

Vibeke Strand, MD: What the money says to do. And the other part of it is that we do know that there are very large patient-support programs for most of the reference product manufacturers. And some of them are really very comprehensive. Now, we can anticipate that the biosimilar manufacturers may offer similar types of programs, but we have to find that out.

Gary R. Lichtenstein, MD: One of the things also, Peter, to recognize is—taking the other side—there are many individual changes that have occurred in the manufacturing of the originators over the years. If you look, for example, at infliximab (Remicade, initially), at least the last I looked at the different patents, there were over 35 different changes in manufacturing since inception in 1998. So, one could say that there have been changes, and if you look at 1 plant versus another plant, there may be some variability. To that mind, there’s at least some comfort, if you would, in those that are academically focused.

Vibeke Strand, MD: But see, those manufacturing changes were how we actually learned how to develop a biosimilar, because the characterization that has to be done once you make a manufacturing change gets more and more specific, depending on how large a change it is or even if you’ve built a whole new plant (which, of course, happens with the reference product). This has actually happened with all the biologics.