Biosimilars: What Are They and What Are Their Advantages?

Jamie DePolo: Hello, everyone. Welcome to this edition of the Breastcancer.org podcast. I’m Jamie DePolo, the senior editor of Breastcancer.org. Today our guest is Dr. Philip Lammers, a medical oncologist who’s the chief of the Division of Hematology and Oncology at Meharry Medical College and adjunct assistant professor of internal medicine at Vanderbilt University. He has several active research projects on ways to increase minority and underserved population representation in clinical trials. He also studies state-of-the-art cancer treatments including biosimilars, which is the topic of our podcast today.

Dr. Lammers, welcome. Thank you for being here.

Dr. Philip Lammers: Hello. Thank you very much for having me today. I’m happy to join you in the podcast.

Jamie DePolo: So to start, how would you describe what a biosimilar is? How would you explain it to somebody who has no medical background?

Dr. Philip Lammers: : The concept of biosimilars is a little bit [of a] different concept for folks to think about, and I think it causes some confusion for some folks. In some ways it’s very similar to a generic medication, but there are ways that it’s a little bit different. So, generic medications are generally chemically made chemical structures. We can create them in the lab by adding certain amounts of this chemical and certain amounts of that chemical, and we can come up with a chemical structure where they’re basically equivalent to the standard medication.

Biosimilars are different, and it’s really because the product that they are being made to be similar to is what’s called a biologic medication. So over the last 20 years in oncology specifically, we’ve seen a rise in biologic treatment options for folks, for patients with breast cancer and other cancers. And these biologic medications are generally proteins, and proteins are very different from kind of general chemical compounds. Proteins not only have the chemical makeup, but they also have different ways of folding on themselves and different structures that are just a little bit different from chemical compounds. So it’s actually impossible to create kind of a generic protein or a generic biologic drug.

And so biosimilars are really medications that are very similar to these biologic drugs or compounds. So in breast cancer, there are several biologic drugs that are used such as trastuzumab or Herceptin, pertuzumab or Perjeta, and several others that are here and on the way. And so companies are now developing these biosimilar medications to be very similar to the reference product, to the initial biologic medication. So in some ways, people can think about them as similar to generic medications but just a little bit different.

Jamie DePolo: One of the biggest things in my understanding is that a biosimilar -- it’s because the biologic is made from living things as opposed to a generic, which is a copy of just a drug that’s made from chemicals, which are not alive. Is that fair?

Dr. Philip Lammers: Yes. That’s very true. So in general, the FDA and the European societies have come up with pathways for these drugs to be approved, which vary quite a bit from the innovator product, or the initial drug that has been approved. So when an initial drug is tested for efficacy in patients with cancer, it often goes through several different clinical trials to show efficacy.

In biosimilars, it’s a little bit different, but really the goal of the biosimilar drug is to be as similar as possible to the existing drug, or the existing biologic drug, in structure, and in toxicity, and in some ways in efficacy. But the process is very much weighted towards early trial designs where you’re testing the biosimilar drug in the lab to make sure it behaves very much like the biologic drug, to make sure it has the same pharmacokinetics, or the way that a drug is eliminated from the body, the way that it is taken up by the body, to the original drug. And so a lot of the testing that’s done on these drugs is actually in the very early stages, where we want to make sure the drug structure is very similar, where the drug behaves very similar in the lab but also in humans. But there is far less amount of testing done on efficacy.

So sometimes when new drugs come out, we have big clinical trials that try to recruit 1,000 patients or something around the world, whereas these biosimilar drugs may have very much smaller trials, where they accrue maybe 300 or 400 patients, and they’re really just trying to show that they work the same or in a similar way as the original product. So the approval process is different. The FDA has really said, “We want these drugs to be very similar but we are not going to try to reinvent the wheel. We’re not going to try to do lots of big clinical trials that have already been done in the reference product.”

Jamie DePolo: Now, what about the approval process for biosimilars? I understand it’s slightly different than a generic and also slightly different than the reference product that it’s similar to?

Dr. Philip Lammers: That is correct. So, proteins you can’t really just make by putting different chemicals together. Proteins have to be made actually from a living cell or a living organism. And so that’s one of the ways that these biosimilars are different than kind of your standard generic compounds in that biologic medicines and biosimilar medicines are all made from living cells.

Jamie DePolo: So the idea being that if the manufacturers of the biosimilar drug show that it’s extremely close to the reference product, the original product, and the dose is the same, then the idea being that yes, it’s going to behave the same in the body and we don’t need to do as much testing like in phase III trials like we do with a brand new drug?

Dr. Philip Lammers: Yes. That’s exactly correct. So you’re really looking at that biosimilarity in the early testing but not necessarily in large clinical trials.

Jamie DePolo: So I know some people are wondering then, how can we be sure if we don’t have as much testing? How can we be absolutely sure that biosimilars are as safe as the reference products?

Dr. Philip Lammers: That’s a good question, and the FDA has laid out some very strict, stringent guidelines for these drugs where they’re really looking at safety first, and they’re also making sure that the drugs are very similar to the reference product. So in many ways, the early part of this testing on these drugs is very similar to what the other drugs that are already on the market had to go through. So they had to show safety, for sure, and have to show similarity, in this case, to an existing product. So the safety requirements are really pretty similar to the existing drugs in these sort of situations. So the FDA has laid out very strict ground rules that the companies have to follow to prove that these drugs are going to be safe for our patients.

Jamie DePolo: Why do we have biosimilars? What are the advantages, and are there any disadvantages? I’m assuming, like generics, it’s got to do with cost, but are there other advantages?

Dr. Philip Lammers: Yeah. Really cost and access. So, a number of studies have been done over the last few years to show places around the world where it’s almost impossible for patients with breast cancer to get access to some of these lifesaving drugs because of how expensive they are and how difficult it is to get to some parts of the world. And surprisingly to some of us, there have been studies showing in the United States, certain populations, elderly patients and minority patients in particular, don’t get the same treatment and often don’t get the exposure to some of these drugs that other people do.

So I think the big advantage of these drugs being on the market is, number one, hopefully it will bring down the costs of these drugs. These biologic medicines for cancer are some of the most expensive medicines out there today, costing hundreds of thousands of dollars for one patient for a year of treatment in some cases. So as with anything in the market economy, if there are multiple drugs on the market, we hope that the cost will come down. And because there will be more companies participating in making these drugs, we also hope that more people around the country and the world will have access to these wonderful biologic drugs.

Jamie DePolo: I have read a couple of things saying that because the process of making both a biologic drug and then the biosimilar copy of it is very involved, it’s much more involved than making a chemical-based drug like aspirin, that some people are wondering if the price is really going to be that much less expensive, or do you think it’s just because now there’s competition so the price will have to come down?

Dr. Philip Lammers: That’s a great question. So number one, these drugs are never going to be as cheap as our generic blood pressure medicines or as aspirin, those type of medicines that are very easy to recreate in generic labs throughout the country. As you mentioned, the process of making these, because they come from live cells, they are very complicated proteins, they have to be treated in certain ways and followed in terms of manufacturing processes very closely.

You’re right. The cost is always going to be high for these drugs, but we hope that there will be at least a cost savings with these drugs. Now, it’s not going to be $10 instead of a $10,000 drug, but we hope that maybe the price will come down 20% or 30% in some cases. And just across the board with the number of women and patients around the country that can benefit from these drugs, we hope that the healthcare cost to the country as a whole will certainly come down.

Jamie DePolo: Is there any estimate in when we might see a biosimilar approved to treat breast cancer in the United States? I think Herceptin is still on patent until next year, and I’ve also heard that the companies who make the original drugs, the reference products, may be thinking about some legal action because obviously they want to protect their investment. I just wonder, do you think it’s going to be soon? Is it going to be a drawn-out thing? Do we have any idea?

Dr. Philip Lammers: Yeah. Another good question. I think that that’s going to be a tough question to answer. What I will say is there has actually been a biosimilar approved for use in the cancer space. A medication that’s similar to the drug Neupogen, or G-CSF, has come out called Zarxio. And so that drug does not necessarily treat the cancer per se, but that drug is used by physicians to help boost patients’ white count, or immune system, after chemotherapy. So it’s a drug, it’s not used widely. It’s not the long-acting form that a lot of us use more commonly, but that is out and people are using it around the country and so far there haven’t been any major safety issues with that.

But turning to drugs that are used to treat therapeutically, to treat the cancer, you did mention the drug Herceptin, trastuzumab. This drug will be going off patent over the next year or so, and this is when we expect some of these drugs to hit the market. Some of the companies are a little bit further along than others in the production of the trastuzumab biosimilars, but there has been a presentation and a publication of one drug in particular over the last few months, and that drug is being reviewed at the FDA. So it could not become available to patients until the patent of the innovator drug, the trastuzumab, or Herceptin, is up.

And like you said, there may be some legal challenges, they may try to extend the patent on that drug and other drugs, but really this is going to be an issue for cancer patients over the next few years. There are several biologic drugs that will be coming off patent, and Herceptin is one of the first, but this is going to be something that becomes commonplace over the next 10 years, really, as more of these biologics that we’ve been using for 15, 20 years come off their patents and open the door for competitor drugs.

Jamie DePolo: One last question. Do you think there are going to be any issues with insurance coverage for biosimilars, or is it going to be fairly standard, like generics are covered?

Dr. Philip Lammers: Yeah. That’s going to be a great question. You know, I think that we’re all going to have to deal with this kind of in real time and see how things go. I don’t think any of the large insurance companies have come out with any stances one way or the other, but there will be issues with which drugs are on formulary at your oncology pharmacy, and it may differ from one practice to another.

So it’s certainly something the insurance companies are going to be working with, but it’s also going to be something that I think patients are going to want to take more interest in and really take initiative to ask the physicians and the practice where they’re being treated which drugs are available to them. Again, we all hope and think that these drugs are going to be very, very similar to the innovator drug and provide the same benefit to patients, but I think it’s going to be worthwhile for patients to take the initiative and to look into what they will be able to get at their practice and through their insurance company once these drugs become available.

Jamie DePolo: So bottom line is patients are going to continue to have to advocate for their own care, which is something we tell our visitors all the time?

Dr. Philip Lammers: Absolutely. Yeah, and we encourage patients to do the same every day.

Jamie DePolo: Excellent. Well, Dr. Lammers, thank you so much. This has been very helpful and informative, and we really appreciate your time.

Dr. Philip Lammers: I am happy to contribute. Thank you so much for having me.

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