Dr. Hans Herfarth explains biosimilars in this episode of the Chair’s Corner. He describes the differences of biosimilars and biologics, and safety issues with switching from an original drug to a biosimilar. Dr. Herfarth is a Professor of Medicine in the Division of Gastroenterology and Hepatology.
- Biosimilars, Biologics & Generic Drugs
- Advantages of Biosimilars
- Safety & switching
- Keeping track of the names
- Additional resources
Ron Falk, MD: Hello, and welcome to the Chair’s Corner from the Department of Medicine at the University of North Carolina. This is our series on new treatments and today we will discuss a concept known as biosimilars.
We welcome Dr. Hans Herfarth, Professor of Medicine in our Division of Gastroenterology and Hepatology. He also co-directs the UNC Multidisciplinary Center for Inflammatory Bowel Disease Research and Treatment. Welcome.
Hans Herfarth, MD, PhD: Thank you for the invitation, and thank you for having me.
Biosimilars, Biologics & Generic Drugs
Falk: What is a biosimilar?
Herfarth: A biosimilar is a very complex drug which is manufactured by biotechnology. It’s manufactured by a living organism, and that makes them different from the drugs we normally take, which are small molecules or small drugs, and these small drugs are, for example, acetaminophen or Tylenol, they are produced by chemical processes. It’s a biotechnology process, it’s complex, and biosimilars are produced by living organisms—I think those are the main three points.
Falk: Is there a difference between what is known as a biologic drug and a biosimilar?
Herfarth: Yes. A biologic drug is essentially the original drug, approved by the FDA years ago, for example, and a biosimilar is a similar drug—it’s similar, but it’s not identical, but it has similar efficacy and safety—that’s a requirement.
Falk: Give me an example of a biosimilar.
Herfarth: Biosimilars were just recently approved in the United States, at least for inflammatory bowel disease. There are two—they’re called Renflexis and Inflectra.
Falk: We will come more to that detail in a minute, but in other words, it’s a drug, or a couple of drugs that mimic the effect of a well-known drug, and they’re similar to it, but in some ways different.
Falk: What’s the difference between a generic drug—the example you used was acetaminophen, which is a generic drug at this point—what’s the difference between a generic drug and a biosimilar?
Herfarth: A biosimilar is similar to the originator—I call the originator the original biologic. The generic is absolutely identical. Acetaminophen is identical to what we know as Tylenol, which was first on the market. Due to the complex process used for production of biologics, you can never do an exactly identical copy, you can never generate this. Ironically, Remicade, is best described as a biosimilar of the Remicade that we used in 2000. There were several manufacturing processes changed—in total about thirty-six times over the past twenty years—and every time you change a manufacturing process to make it better, to make it more efficient, the batch is not the same compared to the old one. Of course, there are no significant differences—they are in the range of one to three percent, but that is essentially not the same Remicade we used fifteen years ago. If you get Remicade today, it’s a biosimilar of the Remicade you got in 2012.
Falk: If you’re cooking chicken on the grill, it could be the same recipe, but because the place you got your chicken from would be different, they would not be identical. Even though the recipe was the same, the chicken dish would be slightly different. They would be similar, but different.
Advantages of Biosimilars
Falk: What’s the reason biosimilars are used? Why are they created in the first place?
Herfarth: They are significantly cheaper than the originators. This has been shown in Europe, where the biosimilar—for example, Remicade is thirty to fifty percent cheaper than the originator, depending on the country. With that, insurances could economize, more patients could have broader access to biologics. For example, in Hungary, prescriptions for biologics increased, so more patients have access to this excellent drug class, and we hope to see the same thing here in the United States. We hope to see perhaps the insurance premiums decrease for patients getting biologics, and/or a broader access possibility for patients to get biologics in the first place.
Falk: There are a number of autoimmune diseases—inflammatory bowel disease, rheumatoid arthritis—there are many of them, all of which use a biologic class of drugs known as TNF, or tumor necrosis factor inhibitors. There are many of these now, and Remicade is an example of those. When they first came out, they were extremely expensive. What you’re suggesting then, is that over the course of time, biosimilars are helping us decrease the cost and increasing the availability for patients.
Falk: The advantage of a biosimilar, or several biosimilars, is that there are opportunities for physicians and their patients to have a number of drugs in their armamentarium. They have lots of options, lots of possibilities.
Herfarth: If you’re prescribed this class of biologics, for example an anti-TNF agent, like Humira or Remicade, or Cimzia or Simponi, or Enbrel, it could very well be that your insurance says that they won’t cover it and you have significant copays.
Now, with the biosimilars, it may very well happen that your insurance may suddenly approve this anti-TNF therapy for you, because it’s cheaper for the insurance and they’re able to pay for it, so that could be the advantage of broader access, which we didn’t have before, because we just had one type of drug.
Safety & switching
Falk: Are they just as safe as the original drug?
Herfarth: This was a major concern when biosimilars were first introduced. There now have been numerous trials in rheumatoid arthritis and inflammatory bowel disease—and perhaps others—where they test the safety and efficacy of the biosimilar and there were equivalent to the originator. So, there was no difference in the number of side effects and no difference in efficacy. That means as well that they’re not more effective—they’re similarly effective, but not less effective. They’re not safer, but similarly safe, but not less safe. They’re absolutely similar to the originators.
Falk: Are biosimilars, then, interchangeable?
Herfarth: Interchangeable designation is not yet approved by the FDA for any biosimilar that I’m aware of. You can interchange between a biosimilar and originator or between two biosimilars as you like. That safety and efficacy has not yet been shown—it’s been shown for one switch.
The other thing is the dispensing pharmacy doesn’t have to tell the prescribing doctors that they switched to another drug—they can do that by themselves. If you have a patient who has switched to a biosimilar, the pharmacy will tell the prescribing doctor that the patient is getting a biosimilar if the doctor is okay with it. If the doctor approves it, the patient will get the biosimilar. Of course, the patient has a say as well in this, and if the patient prefers to stay on the originator, we will make every effort with the insurance company to get the originator approved. But again, a biosimilar is similarly effective and similarly safe, and one switch between the originator and biosimilar is shown to be safe and similarly effective.
Falk: Is it possible that a patient wouldn’t know that a switch has occurred?
Herfarth: It’s possible, if the patient is not told. Normally, our infusion centers, as far as I’m aware of, the patient will be told that they are switched to a biosimilar. The insurance will write the patient that they will be switched to a biosimilar. This is very important—a patient who gets this letter should call his physician and ask the physician if this is okay.
Falk: This communication between the physician and the patient if suddenly a switch has been made from a drug that the patient has been on for a while to a biosimilar.
Falk: Remicade is one example of the drugs that you have already mentioned. There are biosimilars that have just recently come on the market. Can you tell us about them? You mentioned them earlier.
Herfarth: That is Renflexis and Inflectra—these are two different companies producing the biosimilar. It might be confusing for some patients. Importantly, is to look at the name if you get Remicade, Renflexis, or Inflectra. If there are any questions, you should talk to your doctor. It is really important that you are aware of what you are getting. That’s the major difference—your doctor wouldn’t care if you’re getting acetaminophen or Tylenol, they just want to know if you take it, but in the setting of a biologic, it becomes more important that whoever gets one is aware of what he’s getting.
Falk: If you were the patient, and you were well-controlled on Remicade, or well-controlled on Humira, and now were given one of these biosimilars, would you care?
Herfarth: The point is, if I’m well-controlled and there is an advantage from the insurance standpoint or other standpoints, and I switch, I think I would have no problem, because I’m aware they are similarly effective and similarly safe.
What I would not recommend, is, if you are just barely stable on the original drug, to switch then to see if you are more stable on the biosimilar. It’s a similar drug, so you will not be more stable. It’s just too risky to switch you in this setting. There’s a higher risk that you lose response. I think patients that are stable can be safely switched to a biosimilar, and vice versa, because it could very well be that insurance would approve to start with the biosimilar, say Renflexis, and then you move to another state in the United States, and the next infusion place has only Remicade available, and you switch to Remicade—that’s fine as well. You can switch from the biosimilar to the originator.
What you shouldn’t do, is to get one-time Renflexis, which is a biosimilar to Remicade, one-time Inflectra, a biosimilar to Remicade, and the next time Remicade. You should not get multiple drug switches in a short period of time, because we don’t know yet if this is safe. The next few years will tell us if this is safe, to switch back and forth between biosimilars and Remicade. This is the interchangeability we discussed—but at the moment, one switch seems to be safe. I would not recommend several switches, at least not in a short time period.
Falk: There are individuals who develop inhibitory antibodies that decrease the efficacy, or how well certain biologics work. If you have developed an inhibitory antibody, for example, to Remicade, is that same inhibitory antibody going to decrease how well a biosimilar works?
Herfarth: Absolutely. These antibodies are what we call “cross reactive.” We have a similar large molecule and there is a high chance—I would say above ninety percent chance that you develop the same antibodies against a biosimilar. Developing an antibody against the originator will not help you to respond to a biosimilar. You will have a similar reaction, or similar no response to the drug. If you stopped responding to the originator, the biosimilar will not be any better than the originator.
You can make the same assumption for, if you take Tylenol, acetaminophen will not be any better if it doesn’t work. If you take Excedrin, which is a different composition of drugs together for your headache.
Falk: The time to switch, when it’s safe to switch is if you’re stable, you’re doing well, there’s clear communication between the physician and the patient, and agreement of the physician and the patient to switch to a biosimilar. Under those circumstances, the switch from the original drug to the biosimilar is okay.
Herfarth: Yes, absolutely.
Falk: If the patient is not really stable on the original drug, moving to a biosimilar is not a really good idea. If the patient has developed an inhibitory or cross-reactive antibody to the original drug, they have a high likelihood of having the same response—or absence of response—to the biosimilar.
Keeping track of the names
Falk: There are so many names of all of these drugs. They’re all in the same class, they’re really all anti-TNF drugs that have been incredibly effective for a number of patients with autoimmune disease. So, it can be very confusing for a patient, and quite frankly, for the physician, to keep track of one drug or another. What recommendations do you have for patients, and for physicians, not to get confused?
Herfarth: I think we clearly have to develop systems to follow the patient to know what they get. We are trying to implement this in our clinic, that we are aware of what type of anti-TNF the patient is on—before, we didn’t need that because there was only one Remicade. We have, first of all, the brand names which are different—Remicade, Inflectra, and Renflexis. The generic names are easier to remember—everything is infliximab—if it’s a biosimilar or an originator. The biosimilars have four letters adjacent to their name, for example, Inflectra is inflixumab-dybb. I don’t know where this is coming from—the FDA made this recommendation. Whenever you see inflixumab plus something at the end, it’s a biosimilar, and then you should be aware that you’re getting this biosimilar. Same will be true—we don’t have the biosimilars yet—for Humira, the generic name is adulimumab, so there will be four letters at the end of adulimumab.
Falk: It’s going to be the same four letters?
Herfarth: No, it’s not the same four letters. For example, Renflexis has the four letters ABDA—don’t ask me where this is coming from—it could be the adulimumab is XYZ-D for example.
Falk: So, it’s the name, probably with a hyphen, and four letters of some kind, is a clue that you’re getting a biosimilar product.
Herfarth: Yes, and patients should really be aware of their therapies as well. I think the modern computerized patient records make this possible. For example, UNC has the EPIC system and something called MyChart, and you can look in MyChart to see what kind of drugs you’re getting and you can follow these. You should be aware that what is in MyChart is correct and updated. If you have any questions about a medication, you should immediately talk to your doctor if you feel there is something wrong in the MyChart documentation.
Falk: Or if a switch has occurred and you didn’t know this happened.
Falk: Is there a good resource that patients can turn to for more information about biosimilars and how to identify them?
Herfarth: The FDA has a website, but I think I would recommend more patient advocacy groups. In my field, that is the Crohn’s and Colitis Foundation. They made a whole website about biosimilars with frequently asked questions. I’m very sure that for every autoimmune disease, patient advocacy groups have sites on biosimilars. I’m sure if you Google “biosimilars” there will be a lot of websites popping up, but I would recommend the FDA or the patient advocacy groups, like the Crohn’s and Colitis Foundation.
Falk: Thank you so much for helping us understand biosimilars and the original drug.
Herfarth: Thank you for having me.