Biosimilars 101 & Inflammatory Arthritis | Ep. 68
Access will soon expand for new biologic treatments for inflammatory arthritis called biosimilars. Learn what they are, what to expect when taking one, including safety and effectiveness, and how determine if they are right for you. Scroll down for show notes and full transcript.
We would like to thank the Amgen for their support of our biosimilar education resources.
Show Notes
If you have an autoimmune, inflammatory type of arthritis, like rheumatoid arthritis, psoriatic arthritis or axial spondylarthritis, or you have a child with juvenile idiopathic arthritis, you’re probably familiar with the class of medications called “biologics.” For many of with autoimmune arthritis, these drugs are life-changing, and access to helps keeps disease under control and slow progression.
In this episode, we’ll explore little known and understood biologic treatments for autoimmune and inflammatory arthritis, called biosimilars. We’ll hear from a rheumatologist familiar with prescribing biosimilars to help manage inflammatory forms of arthritis, including biosimilars basics, what to expect when taking one and how to determine what’s best for you.
About the Guest
Mark S. Box, MD, FACR, FACP (Kansas City, KS)
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About the Hosts
Rebecca Gillett, MS OTR/L (Denver, CO)
Read More About Rebecca
Rick Phillips, Patient Leadership Council Member (Noblesville, IN)
Read More About Rick
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Full Transcript:
Released on November 22, 2022
PODCAST OPEN:
You’re listening to the Live Yes! With Arthritis podcast, created by the Arthritis Foundation to help people with arthritis — and the people who love them — live their best lives. If you’re dealing with chronic pain, this podcast is for you. You may have arthritis, but it doesn’t have you. Here, learn how you can take control. Our host is Rebecca Gillett, an arthritis patient and occupational therapist, who is joined by others to help you live your Yes.
MUSIC BRIDGE
Rebecca Gillett:
Thanks for joining us on this episode of the Live Yes! With Arthritis podcast. If you have an autoimmune inflammatory type of arthritis like me — like rheumatoid arthritis or psoriatic arthritis, or axial spondylarthritis, or maybe you have a child with juvenile idiopathic arthritis — you’ve probably heard the term for the class of medications called biologics. For many of us with autoimmune arthritis, these drugs are life-changing, and access to them keeps our disease under control and can slow the progression of the disease.
In today's episode, we're going to talk about a little known and understood biologic treatment for autoimmune and inflammatory arthritis called biosimilars. We'll hear from a rheumatologist who is the expert in this area and familiar with prescribing biosimilars to help manage inflammatory forms of arthritis, including: biosimilars basics, what to expect when talking one and how to determine what's best for you. Returning as a guest co-host with me again is Rick Phillips.
Rick Phillips:
It's great to be here.
Rebecca Gillett:
Rick is also on our Patient Leadership Council. As patients who take biologics, we all have many questions. There's a lot of people out there with concerns.
Rick, I'm so excited to have Dr. Mark Box with us on the show today. He is board certified in rheumatology and a clinician who specializes in bone density scanning and monitoring. In addition, he is a member of the National Board of Medical Examiners, American College of Rheumatology and the Coalition of State Rheumatology Organizations. Dr. Box, thanks so much for joining us.
Dr. Mark Box:
Thank you.
Rebecca Gillett:
First, please explain to everyone listening: What is a biologic versus a biosimilar?
Dr. Mark Box:
Biologics are medications that we use to treat autoimmune diseases. There are other uses for biologics — including cancer, chemotherapy, multiple sclerosis, anemia — that are used. But we used them extensively since the first biologic drug came along in 1998, and that was etanercept, or Enbrel.
Biologics are drugs that are produced in living tissues as modified to produce specific types of antibodies. These drugs are used to treat autoimmune diseases such as rheumatoid arthritis and lupus.
The drugs, like small molecule medications, have a certain patent or exclusivity for the company that develops them. Once that exclusivity expires, then other companies are allowed to come in and make competing products of that same molecule. Since you can't exactly replicate these molecules because they are made in living cells, the add-on medications, or the follow-up medications, are called biosimilars.
Rick Phillips:
Dr. Box, we are coming into a brand-new era when there will be very large-scale introduction of biosimilars in the U.S. market. Do I understand that Europe has had biosimilars for a much longer period?
Dr. Mark Box:
They have. We've had biosimilars close to five years with the drugs in the rheumatology field. I think for infliximab, or Remicade, the biosimilars were approved about five years ago, so they've been around for a while, and then, more recently, rituximab. These were drugs that were in the IV infusion suite space, and so, many people didn't really necessarily recognize that something might be changing there because that really was more what the physicians were doing based on what your insurance might require as the preferred drug.
Starting January 1 st , adalimumab, or Humira, will be going biosimilar. There will be introduction over the next several years of many drugs that are the biosimilar to what is the most widely prescribed biologic drug in the world. In Europe, they've been around for even a longer period of time. Their patent system was a little bit more lenient in introducing these medications, and so, for essentially the major TNF inhibitors — infliximab, Humira, Enbrel — they’ve had biosimilars going on for at least about five years.
Rick Phillips:
There's really not been patient-reported difficulty with biosimilars in Europe during that period.
Dr. Mark Box:
Yes. A biosimilar has to be a drug that is highly similar to the referenced product, with no clinically meaningful difference in its safety, efficacy or potency. That has to be proven before these drugs can be approved, and they have to go through very extensive testing before they can be brought to the market and the FDA approves them. That's the same thing for the EMA, which is the European Union's version of the FDA.
These drugs are not being made by fly-by-night, small, generic companies. Anybody can make a small molecule relatively easily. These are very, very complex drugs and take very, very complex methods to make. And so, the companies that you see in this market are already in the biologic market.
You basically take a molecule of the originator product. You learn the amino acid sequence of it. That's very easy to do. You can make a molecule that is 99 and 9/10% similar to the original one. One of the things I always tell people to try to realize is that these are made in living cells. Every batch of the originator product can be slightly different, as it is now. But they have to go through a testing process, even with the originators, to show that the potency, efficacy and safety are similar to what they have had over the decades that the medicines have been around.
Rebecca Gillett:
What I think our listeners will hear a lot of is reference biologics, so when we say reference biologics, those are the original drugs that came out, right?
Dr. Mark Box:
Right, yeah.
Rebecca Gillett:
So, that’s the original product. The other thing that I want to touch on, too, is these are biosimilars, and they're called biosimilars and not generic. They're not the same as generic drugs. What is the difference?
Dr. Mark Box:
A generic drug is usually a small molecule, and that's what we call oral medications that you take. Just to kind of give you an idea: Molecules are measured in a unit called daltons, and so an aspirin is something that weighs about 180 daltons. A biologic product like infliximab, it weighs 149,000 daltons, so you're talking about much, much different type of products here.
One is made in a cell, the other is made purely in a chemical reaction. A generic is exactly the same substance as the originator, so an aspirin, whether it's made by Bayer or whether it's made by CVS or whether it's made by Tevia, is exactly the same salicylic acid.
With a biologic product, because you're making a cell line to which you have inserted genetic material to make it make what you want, you are depending on that cell to make something that's very similar because it's got the genetic code, which is essentially exactly the same. The cells do a little bit different.
That has never been something that has been clinically considered significant, because when you look at the efficacy, meaning: Do they bind up the molecule that you want them to bind up in equal quantities? They are overlapping in terms of how well they work between the products that have been approved by the FDA.
Rebecca Gillett:
I think that helps to clarify that for some people, but I still think there are going to be people who are worried. When you say they're not the...
Dr. Mark Box:
Not the exact.
Rebecca Gillett:
...they derive from living organisms, but they're not exactly the same. Should they be concerned about that?
Dr. Mark Box:
Well, I mean, there's always this concern about what's called “nocebo effect,” so when you're concerned about something, you're more likely to have a negative reaction to it. For example, when infliximab was made as a biosimilar, the companies had to do studies with rheumatoid arthritis patients, where they gave each group not the placebo, but the originator product and the biosimilar, the outcomes were the same. The outcomes were the same in ankylosing spondylitis, they were the same in psoriasis, they were the same in Crohn's disease.
In a case where you're blinded and don't know what you're getting, the outcomes are the same. I can't say that objectively I've seen any examples of someone not doing as well with a biosimilar as they did with the originator.
TYLENOL COMMERCIAL
Rick Phillips:
Dr. Box, what is the main reason for prescribing a biosimilar?
Dr. Mark Box:
It's mainly driven by insurance companies. Early on, when the biosimilars came on… Pharmaceutical companies are aggressive. They market their drugs, and in some cases, the originator companies were able to keep the contracts with the insurance companies. Because of the downward spiral of the cost of the medications, with the competition being there, some insurance companies mandate that when we start someone on a new infliximab, that's the Remicade class, we must use the biosimilar for initiation for a new patient.
Most of them are still allowing us to maintain the originator product for people who are stable on the medication. But even in some cases, insurance companies are demanding that you use a biosimilar, and that's really cost. We actually started using the biosimilars on our Medicare patients early on because it was a cost-effective measure for us in the office to use that biosimilar, feeling that we were giving the patients the same level of care. I really found no instances of adverse or loss of efficacy more than I would expect over time with these type of medicines. People do lose efficacy with biologic drugs. That has to do with their own immune systems, but I don't believe it has anything to do at this point that I've seen with biosimilars.
Rick Phillips:
When a person gets a new medication, a new injectable, and they expect to get medication X, but it really is a biosimilar, it will not have the same name. Is that correct?
Dr. Mark Box:
Correct. Going forward from January 1 st , 2023, those individuals who are on Humira may find that in order for them to maintain that medication, their insurance requires the use of the biosimilar drug for it. They will be labeled with the generic name adalimumab, followed by a four-digit code that is just a random set of letters. The biosimilar companies can actually put a brand name on their drug, so you'll see a brand name and then adalimumab ZZPQ to indicate that it is the biosimilar to Humira.
Rick Phillips:
I think that the great angst among patients is going to be when they receive that different named medication for injection.
Dr. Mark Box:
In the first six months, there's only going to be one competitor to Humira, and, interestingly, that is the drug that is going to be made by Amgen, who makes Enbrel. They made the first biologic drug that came on the market 25 years ago. I think that can be a very reassuring thing to patients: that this is a company that knows how to make a drug.
What you have to look at is what we're saving for the health care system in this country, which we do have to understand is being strained by these medications. By reducing costs, we will, I think, allow people to continue to get these medications in a less restrictive fashion, and we will also save money for the next day so that the system doesn't go broke.
Rick Phillips:
You also think that it will spur further development in biologics as some of the patents roll off? I believe that companies who had those original patents and other companies will see the possibility of expanding the offerings.
Dr. Mark Box:
Oh, yes. The pipeline in rheumatoid arthritis, lupus, psoriatic arthritis, is pretty deep. I mean, while you might consider that these are relatively rare diseases: 1% of the population has rheumatoid arthritis. Between 1998 when Enbrel came on and now, if you think of the number of new products that have been produced in this space to treat rheumatoid arthritis, it's still a very lucrative market for the pharmaceutical companies.
It's still a lot of unmet need because we still, at this point, have 20% of patients with rheumatoid arthritis that don't completely respond to the medicines that we have. And so, I don't see this as slowing it down. I do see it as saving a lot. I think the best example to look at is infliximab. Infliximab five years ago cost $850 a vial when there was one company making it. Now, it's a little less than $350 a vial, so it's reduced by $500 a vial.
Some parts of the world don't have these drugs because they are too expensive: Eastern Europe, South America, where they couldn't get these medications, and now infliximab is becoming more available to them through this reduced cost.
Rebecca Gillett:
I know for me and for you, Rick, when we were first diagnosed 20-some years ago, there were like two options. I've been on almost every TNF blocker. Now, I've had options over the years. There's been different drugs targeting different parts of your immune system that have come along, and there's a lot of options for us out there.
The one thing that has been very scary for me every time I've had to switch a medication is that I've had to switch a medication and the unknown. There was a reason to switch, and it was: “This was not as effective as the one I’m on now. I’m still having flares. I’m still having pain. I’m not sleeping.”
PROMO:
Biologics and biosimilars. What’s the difference? And what does it mean for you? It can be confusing. That’s why the Arthritis Foundation provides guidance on what to consider in your own situation. Get the facts from the arthritis community’s most-trusted source of information. Visit https://www.arthritis.org/biosimilars .
Rebecca Gillett:
There's always a fear of switching medications, and so, to know that these drugs are out there, how do we calm everybody's fears? How can they be proactive with their doctor and with their pharmacy and with their insurance and understanding what they're going to have access to?
Dr. Mark Box:
I think in the beginning you're probably not, in this next year, 2023, going to see a big difference. Humira will probably still be the... If you're on that TNF inhibitor, that's probably still what you will get. In the beginning, when that first biosimilar comes along, it may be new starts. So, that will be your new start from the beginning, but I don't think people established in most cases will be forced to change. As time goes along, we may find that what your insurance company requires, in order to maintain that product, is a different brand of it.
I think people should try to be reassured that these drugs are high quality. They are highly similar. The likelihood of them not doing exactly the same thing is infinitesimally low. I wouldn't anticipate, changing from the originator to the biosimilar, that you'll have any difference because really, in those people who are blinded to this process, they don't have any difference. European countries have, and in many cases on a yearly basis, changed what drug is available to their population and not seen adverse reactions.
I think you have to be reassured that there is a quality system here that is outside of any politics or anything else that we worry about that has really reassured that these drugs are available. This is an evolutionary process that has been going on for a decade.
Rebecca Gillett:
From the Arthritis Foundation's perspective, we do hold a position. If you want to read our position statement on our website, at arthritis.org/biosimilars, you can find the full statement. Basically, our position is that these drugs are equally effective and safe, but we are ultimately patient advocates, and we are here to support you and advocate for you. It should be up to you and your doctor if you want to switch, especially if you are in a remission or your disease is stable.
Just have this conversation with your doctor, so you know. Then, call your insurance and find out: “Do you have plans for any changes on your formulary of what you’re covering and how you’re covering?” Just make sure you take the lead. You hold the ball in your court when it comes to advocating for yourself.
For me personally, it's comforting to know that it's been used in the European countries for many years. I know patients who are excited about the promise of lower costs because I know there are patients out there who haven't even had access to biologics and will want to make a switch. How do they start that process? How should they approach that with their doctor?
Dr. Mark Box:
Well, again, so much of this in our country is dictated by what the insurance formulary says. And so, if you're a Medicare patient with IV medications, in those cases there is more of a choice of using a biosimilar versus using the originator product.
With commercial insurances, usually when we send in for an approval for, say, Remicade, they may come back to us and say, "In order to get access to Remicade, you must fail X, Y and Z," which are usually one or two of the biosimilars. Sometimes there is no way around that. It's like, "You will not get anything if you don't do these, period."
I think as new starts are coming along, that's where we really will see the opportunity to let people start with a new product. I have no idea, starting January 1 st, whether Amgen's Humira biosimilar is going to be available on any given insurance plan. We'll have to see, when we start sending in requests for prior authorization, what comes out.
Rick Phillips:
I use rituximab, and I have asked the last two times if the biosimilar's available and if it could be used. Because I'm very excited about the prospect. So far, I've not been able to get it, but I know it's coming, and I am very excited about it.
Dr. Mark Box:
It's interesting that infliximab's been a biosimilar for maybe five years, rituximab only for about year or so. But now we are seeing that when we have new starts, they are demanding Truxima or Ruxience, which are two of the biosimilars for that being the starting product for patients. They are available, and for Medicare patients that would be an option to discuss.
Another issue here is inventory management and control, because it's going to be hard to try to keep, for the IV world, too many different products in your refrigerator for this patient and that patient, depending on what the demands of their insurance are for products.
We've actually gone a couple of times and said, “OK, we'll happily use a biosimilar for your patients, but this is the biosimilar we’ve got in the refrigerator, and this is the one we’re going to stock. Will you let us use it?” We've usually won those cases with them. We still have gone to using a biosimilar, but we haven't used their preferred biosimilar.
Step therapy will apply to biosimilars in a way. Because now what we are seeing with the infliximab infusions are that they are requiring that, in order for you to get the originator product, that being Remicade, you have to have failed one or two of the available biosimilars in order to get that originator product. That's a different form of step therapy, but it is there.
Rebecca Gillett:
I do want to define step therapy for those that don't know what it is. And that is a practice of being told to fail first. So, whatever drug your doctor prescribes you, you're expected to fail that drug first before insurance will cover the drug that the doctor has prescribed for you. Basically, insurance is somewhat dictating what medication you're doing. That is something that we have been successful at the Foundation in advocating for in many states across the U.S. and have been working hard for many, many years to try to get a national bill supported for limiting that practice.
Dr. Mark Box:
That is something that is a big area of advocacy both in the Arthritis Foundation and the Coalition of State Rheumatology Organizations and the American College of Rheumatology — to try to stop this capricious process of step therapy.
Rebecca Gillett:
If somebody ends up taking a biosimilar, are there any side effects they can expect to experience? Are they the same kind of side effects from the reference biologic?
Dr. Mark Box:
Here's the only thing that right now I could say that may be a difference: Several years ago, both Enbrel and Humira, which are the TNF inhibitors that are Sub-Q injectables, changed their formulas so that they took out what was causing them to sting…
Rebecca Gillett:
Citrate-free…
Dr. Mark Box:
Yeah, citrate-free, or phosphate-free with Enbrel, and so that did make a difference. People found them to be much more comfortable. I don't know at this point in time with these biosimilars how well they're going to do. I would really assume the first one from Amgen, who's done this with their Enbrel already, by taking out the thing that caused the burning discomfort, that they will probably do the same thing.
I think the only difference you may feel is if the buffer that's used with it is not citrate-free, that there could be some burning again. That may be a good reason. I mean, that would obviously be a reason to say, "I can't take this," and we go back. OK, but you've tried what it is.
I don't believe that you will have a difference in how well that drug works for you. You should have no more likelihood of an allergic-type reaction to this one, because it is the same molecule. It's a humanized molecule. It should not in any pharmacological or medical sense cause you to be more likely to have any problem with it than the originator product.
I think they all will know that if they want their product to be successful on the market, it has to be citrate-free, and they have to have a friendly type of pen, and it may be even better.
Also in our system, the copay cards are very, very important. Big companies are going to come out with the same type of copay cards, the same type of patient assistance programs that are important to the affordability for the individual of these medications. I suspect that five years from now, we will see the price of Humira drop by probably 50 to 75%. There will be a bottom point of which it can't drop any lower because manufacturing of these is way too expensive for it to go down to what we would think of as oral generic drugs. But it will be less.
Rebecca Gillett:
Well, that's the good news, right? Easier on the pocket for the patient, which it's always not easy, because there's a lot of medications and copays to pay for. It does ease some of that financial burden on the system as it were, as you said, especially the patient.
PROMO:
Whenever you need help, the Arthritis Foundation’s Helpline is here for you, now offering support in Spanish and other languages. Whether it’s about insurance coverage, a provider you need help from or something else, get in touch with us by phone, toll-free, at 800-283-7800. Or send us a message at https://www.arthritis.org/helpline .
Rebecca Gillett:
I'm going to move to our listener segment. We posed a question on social media to hear from our listeners about biosimilars and if they even knew what they were. We asked: "What do you know about biosimilars to treat autoimmune inflammatory arthritis? What are your concerns?" One person just mentioned that insurance isn't covering it yet, and then somebody did ask, "Are they injections or pills?"
Dr. Mark Box:
To use the term "biosimilar," it must be a biologic product. All biologic products have to be injected or infused. There will never be a true generic of any of these injectable or infusible drugs. They will always be considered to be biosimilars because they have to be made in living organism tissues.
Rebecca Gillett:
Well, that answers that question. But it also brings up another point, though: If it is an injectable or an infusion, the biosimilar version of it would be an injectable or an infusion?
Dr. Mark Box:
Yes. If they're going to call it infliximab YYCA, then it has to be administered in the same dosings in the same way as the originator product. If you look at the package label, the dose range, the dose interval, are exactly the same as the originator, and the same thing will be for Humira and their biosimilar. It will be a subcutaneous injection of 40 milligrams every two weeks. Can be accelerated to weekly with certain diseases or certain processes. There would be no other difference.
Rebecca Gillett:
On Instagram, we asked, “What is your biggest concern about being switched to a biosimilar?” Somebody mentioned paying for it and insurance authorization and dealing with specialty pharmacies. That whole process is probably going to be the same?
Dr. Mark Box:
It's going to be exactly the same. Some of it in the beginning will be driven through the doctor's office. When we try to get an authorization, or we try to get your renewal, your insurance company's going to come back and say, "This is our preferred product in this category. Have they failed this one?" That's where it's going to come from in the beginning, as I see it.
Now, as we get more comfortable with these, we may choose, as physicians, to say: “You're a new start. We're going to use this biosimilar as your new start, mainly because I know your insurance company will approve it.”
Rebecca Gillett:
OK. Somebody does mention they're concerned about starting a new one, seeing potential with it, and then insurance pulling out from under them and “having me change because of the cost.” What do you think about that?
Dr. Mark Box:
That's something that probably will be realistic. But again, I think you need to be reassured that you are getting a 99 and 9/10% similar product. Hopefully, as these become less expensive, you're going to be less likely to have the whole class pulled out from underneath you than anything else.
Rebecca Gillett:
EGoldstein7 mentions: developing antibodies again.
Dr. Mark Box:
Anti-drug antibodies is something that happens because, these at best — even when they're humanized and made so that your body won't recognize them as foreign — they are foreign. You're injecting something foreign, and our body's normal response to foreign substances, coming in like viruses or a splinter, is to have an immune reaction to them.
Originally, there was this concern, with infliximab products, that if you had to change them too often, even those subtle differences might lead to you forming antibodies against it. The studies have not supported that. And with the adalimumab/Humira products that are out there… there are, I think, seven of them right now FDA-approved.
Only one of them will be marketed in the first six months.
But of those approved products, two of them are actually considered interchangeable. They did studies where they switched people back and forth multiple times during the period of a year, between the originator and the biosimilar, and didn't see antibody formation. So, they were allowed to say that their product is truly interchangeable.
Now when we're sending something to a pharmacy for Humira, once these two interchangeable products are there, the pharmacist will be allowed under law to dispense whatever is the least expensive product on his shelf to you. I don't have to purposely write that, “Your Humira.” Unless I've written “do not substitute” on the Humira prescription, that will be allowed. Just like right now: I write for Lipitor. It's very doubtful you're going to get brand name Lipitor; you're going to get a generic that's on the shelf in the pharmacy.
However, one thing to note is that laws exist in all states saying notification must be given to the doctor and the patient, within three days, that what has been dispensed is the biosimilar instead of the originator product. That will not happen immediately, because those products that are interchangeable are not the ones that are going to be on the market for the first six months. But they will come. And so, we will see more of that ability of the pharmacy to substitute immediately or from the beginning, the products. That is because they have done the studies to show that there isn't any reaction…
Rebecca Gillett:
Right, through the patients. You just introduced an important term that we're not going to really get into a lot of detail on this podcast, but “interchangeable.” Just as you said, those interchangeable biosimilars aren't even going to be out yet in the first six months of the new year. You'll have to check out our website at arthritis.org/webinars. We did a webinar on biosimilars and covered the topic of interchangeables, so look there for more information.
Dr. Box, as we head into the new year and people are anxious maybe about biologics and biosimilars, please share your top three takeaways from today's conversation.
Dr. Mark Box:
These are products that are proven by our FDA to be highly similar with no meaningful difference in their safety, efficacy or potency. That we have to look at these as cost savings to our system and potentially, eventually, to the individual, in terms of being able to maintain these medications. And that the experience out there with these products, which have been back for nearly a decade in some areas, has shown that they’re equally efficacious and that there are no increased number of side effects associated with these medications across large populations.
Rebecca Gillett:
Thank you, Dr. Box. Rick, do you have anything that you want to share?
Rick Phillips:
My top three takeaways… Biosimilars are coming, and that's number one. Number two: It should usher in a new era of affordability, which should broaden access to these very important medications. Number three: I believe it will increase research and development into further advancing this pipeline. I think it will do that because the companies who are currently producing them at a very high cost will want to press forward in order to get the next level of medication, and more competitors is always good.
Rebecca Gillett:
Yeah, you know, bottom line for us as patients is having the better treatments and access to them. And having access for more people to be able to take these drugs is super important. Thank you, Rick.
Go to our website at arthritis.org/biosimilars to find more information and read that position statement from the Arthritis Foundation. Also, I just want to say any information that you have, or you run into any issues, don't forget you can contact the Arthritis Foundation's Helpline. Thank you so much for joining us, Dr. Box. We appreciate it.
Dr. Mark Box:
Thank you.
Rick Phillips:
Thank you.
PODCAST CLOSE:
The Live Yes! With Arthritis podcast is independently produced by the Arthritis Foundation, to help people living with arthritis and chronic pain live their best life. People like you. For a transcript and show notes, go to https://www.arthritis.org/liveyes/podcast . Subscribe and rate us wherever you get your podcasts. And stay in touch!
Released on November 22, 2022
PODCAST OPEN:
You’re listening to the Live Yes! With Arthritis podcast, created by the Arthritis Foundation to help people with arthritis — and the people who love them — live their best lives. If you’re dealing with chronic pain, this podcast is for you. You may have arthritis, but it doesn’t have you. Here, learn how you can take control. Our host is Rebecca Gillett, an arthritis patient and occupational therapist, who is joined by others to help you live your Yes.
MUSIC BRIDGE
Rebecca Gillett:
Thanks for joining us on this episode of the Live Yes! With Arthritis podcast. If you have an autoimmune inflammatory type of arthritis like me — like rheumatoid arthritis or psoriatic arthritis, or axial spondylarthritis, or maybe you have a child with juvenile idiopathic arthritis — you’ve probably heard the term for the class of medications called biologics. For many of us with autoimmune arthritis, these drugs are life-changing, and access to them keeps our disease under control and can slow the progression of the disease.
In today's episode, we're going to talk about a little known and understood biologic treatment for autoimmune and inflammatory arthritis called biosimilars. We'll hear from a rheumatologist who is the expert in this area and familiar with prescribing biosimilars to help manage inflammatory forms of arthritis, including: biosimilars basics, what to expect when talking one and how to determine what's best for you. Returning as a guest co-host with me again is Rick Phillips.
Rick Phillips:
It's great to be here.
Rebecca Gillett:
Rick is also on our Patient Leadership Council. As patients who take biologics, we all have many questions. There's a lot of people out there with concerns.
Rick, I'm so excited to have Dr. Mark Box with us on the show today. He is board certified in rheumatology and a clinician who specializes in bone density scanning and monitoring. In addition, he is a member of the National Board of Medical Examiners, American College of Rheumatology and the Coalition of State Rheumatology Organizations. Dr. Box, thanks so much for joining us.
Dr. Mark Box:
Thank you.
Rebecca Gillett:
First, please explain to everyone listening: What is a biologic versus a biosimilar?
Dr. Mark Box:
Biologics are medications that we use to treat autoimmune diseases. There are other uses for biologics — including cancer, chemotherapy, multiple sclerosis, anemia — that are used. But we used them extensively since the first biologic drug came along in 1998, and that was etanercept, or Enbrel.
Biologics are drugs that are produced in living tissues as modified to produce specific types of antibodies. These drugs are used to treat autoimmune diseases such as rheumatoid arthritis and lupus.
The drugs, like small molecule medications, have a certain patent or exclusivity for the company that develops them. Once that exclusivity expires, then other companies are allowed to come in and make competing products of that same molecule. Since you can't exactly replicate these molecules because they are made in living cells, the add-on medications, or the follow-up medications, are called biosimilars.
Rick Phillips:
Dr. Box, we are coming into a brand-new era when there will be very large-scale introduction of biosimilars in the U.S. market. Do I understand that Europe has had biosimilars for a much longer period?
Dr. Mark Box:
They have. We've had biosimilars close to five years with the drugs in the rheumatology field. I think for infliximab, or Remicade, the biosimilars were approved about five years ago, so they've been around for a while, and then, more recently, rituximab. These were drugs that were in the IV infusion suite space, and so, many people didn't really necessarily recognize that something might be changing there because that really was more what the physicians were doing based on what your insurance might require as the preferred drug.
Starting January 1 st , adalimumab, or Humira, will be going biosimilar. There will be introduction over the next several years of many drugs that are the biosimilar to what is the most widely prescribed biologic drug in the world. In Europe, they've been around for even a longer period of time. Their patent system was a little bit more lenient in introducing these medications, and so, for essentially the major TNF inhibitors — infliximab, Humira, Enbrel — they’ve had biosimilars going on for at least about five years.
Rick Phillips:
There's really not been patient-reported difficulty with biosimilars in Europe during that period.
Dr. Mark Box:
Yes. A biosimilar has to be a drug that is highly similar to the referenced product, with no clinically meaningful difference in its safety, efficacy or potency. That has to be proven before these drugs can be approved, and they have to go through very extensive testing before they can be brought to the market and the FDA approves them. That's the same thing for the EMA, which is the European Union's version of the FDA.
These drugs are not being made by fly-by-night, small, generic companies. Anybody can make a small molecule relatively easily. These are very, very complex drugs and take very, very complex methods to make. And so, the companies that you see in this market are already in the biologic market.
You basically take a molecule of the originator product. You learn the amino acid sequence of it. That's very easy to do. You can make a molecule that is 99 and 9/10% similar to the original one. One of the things I always tell people to try to realize is that these are made in living cells. Every batch of the originator product can be slightly different, as it is now. But they have to go through a testing process, even with the originators, to show that the potency, efficacy and safety are similar to what they have had over the decades that the medicines have been around.
Rebecca Gillett:
What I think our listeners will hear a lot of is reference biologics, so when we say reference biologics, those are the original drugs that came out, right?
Dr. Mark Box:
Right, yeah.
Rebecca Gillett:
So, that’s the original product. The other thing that I want to touch on, too, is these are biosimilars, and they're called biosimilars and not generic. They're not the same as generic drugs. What is the difference?
Dr. Mark Box:
A generic drug is usually a small molecule, and that's what we call oral medications that you take. Just to kind of give you an idea: Molecules are measured in a unit called daltons, and so an aspirin is something that weighs about 180 daltons. A biologic product like infliximab, it weighs 149,000 daltons, so you're talking about much, much different type of products here.
One is made in a cell, the other is made purely in a chemical reaction. A generic is exactly the same substance as the originator, so an aspirin, whether it's made by Bayer or whether it's made by CVS or whether it's made by Tevia, is exactly the same salicylic acid.
With a biologic product, because you're making a cell line to which you have inserted genetic material to make it make what you want, you are depending on that cell to make something that's very similar because it's got the genetic code, which is essentially exactly the same. The cells do a little bit different.
That has never been something that has been clinically considered significant, because when you look at the efficacy, meaning: Do they bind up the molecule that you want them to bind up in equal quantities? They are overlapping in terms of how well they work between the products that have been approved by the FDA.
Rebecca Gillett:
I think that helps to clarify that for some people, but I still think there are going to be people who are worried. When you say they're not the...
Dr. Mark Box:
Not the exact.
Rebecca Gillett:
...they derive from living organisms, but they're not exactly the same. Should they be concerned about that?
Dr. Mark Box:
Well, I mean, there's always this concern about what's called “nocebo effect,” so when you're concerned about something, you're more likely to have a negative reaction to it. For example, when infliximab was made as a biosimilar, the companies had to do studies with rheumatoid arthritis patients, where they gave each group not the placebo, but the originator product and the biosimilar, the outcomes were the same. The outcomes were the same in ankylosing spondylitis, they were the same in psoriasis, they were the same in Crohn's disease.
In a case where you're blinded and don't know what you're getting, the outcomes are the same. I can't say that objectively I've seen any examples of someone not doing as well with a biosimilar as they did with the originator.
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Rick Phillips:
Dr. Box, what is the main reason for prescribing a biosimilar?
Dr. Mark Box:
It's mainly driven by insurance companies. Early on, when the biosimilars came on… Pharmaceutical companies are aggressive. They market their drugs, and in some cases, the originator companies were able to keep the contracts with the insurance companies. Because of the downward spiral of the cost of the medications, with the competition being there, some insurance companies mandate that when we start someone on a new infliximab, that's the Remicade class, we must use the biosimilar for initiation for a new patient.
Most of them are still allowing us to maintain the originator product for people who are stable on the medication. But even in some cases, insurance companies are demanding that you use a biosimilar, and that's really cost. We actually started using the biosimilars on our Medicare patients early on because it was a cost-effective measure for us in the office to use that biosimilar, feeling that we were giving the patients the same level of care. I really found no instances of adverse or loss of efficacy more than I would expect over time with these type of medicines. People do lose efficacy with biologic drugs. That has to do with their own immune systems, but I don't believe it has anything to do at this point that I've seen with biosimilars.
Rick Phillips:
When a person gets a new medication, a new injectable, and they expect to get medication X, but it really is a biosimilar, it will not have the same name. Is that correct?
Dr. Mark Box:
Correct. Going forward from January 1 st , 2023, those individuals who are on Humira may find that in order for them to maintain that medication, their insurance requires the use of the biosimilar drug for it. They will be labeled with the generic name adalimumab, followed by a four-digit code that is just a random set of letters. The biosimilar companies can actually put a brand name on their drug, so you'll see a brand name and then adalimumab ZZPQ to indicate that it is the biosimilar to Humira.
Rick Phillips:
I think that the great angst among patients is going to be when they receive that different named medication for injection.
Dr. Mark Box:
In the first six months, there's only going to be one competitor to Humira, and, interestingly, that is the drug that is going to be made by Amgen, who makes Enbrel. They made the first biologic drug that came on the market 25 years ago. I think that can be a very reassuring thing to patients: that this is a company that knows how to make a drug.
What you have to look at is what we're saving for the health care system in this country, which we do have to understand is being strained by these medications. By reducing costs, we will, I think, allow people to continue to get these medications in a less restrictive fashion, and we will also save money for the next day so that the system doesn't go broke.
Rick Phillips:
You also think that it will spur further development in biologics as some of the patents roll off? I believe that companies who had those original patents and other companies will see the possibility of expanding the offerings.
Dr. Mark Box:
Oh, yes. The pipeline in rheumatoid arthritis, lupus, psoriatic arthritis, is pretty deep. I mean, while you might consider that these are relatively rare diseases: 1% of the population has rheumatoid arthritis. Between 1998 when Enbrel came on and now, if you think of the number of new products that have been produced in this space to treat rheumatoid arthritis, it's still a very lucrative market for the pharmaceutical companies.
It's still a lot of unmet need because we still, at this point, have 20% of patients with rheumatoid arthritis that don't completely respond to the medicines that we have. And so, I don't see this as slowing it down. I do see it as saving a lot. I think the best example to look at is infliximab. Infliximab five years ago cost $850 a vial when there was one company making it. Now, it's a little less than $350 a vial, so it's reduced by $500 a vial.
Some parts of the world don't have these drugs because they are too expensive: Eastern Europe, South America, where they couldn't get these medications, and now infliximab is becoming more available to them through this reduced cost.
Rebecca Gillett:
I know for me and for you, Rick, when we were first diagnosed 20-some years ago, there were like two options. I've been on almost every TNF blocker. Now, I've had options over the years. There's been different drugs targeting different parts of your immune system that have come along, and there's a lot of options for us out there.
The one thing that has been very scary for me every time I've had to switch a medication is that I've had to switch a medication and the unknown. There was a reason to switch, and it was: “This was not as effective as the one I’m on now. I’m still having flares. I’m still having pain. I’m not sleeping.”
PROMO:
Biologics and biosimilars. What’s the difference? And what does it mean for you? It can be confusing. That’s why the Arthritis Foundation provides guidance on what to consider in your own situation. Get the facts from the arthritis community’s most-trusted source of information. Visit https://www.arthritis.org/biosimilars .
Rebecca Gillett:
There's always a fear of switching medications, and so, to know that these drugs are out there, how do we calm everybody's fears? How can they be proactive with their doctor and with their pharmacy and with their insurance and understanding what they're going to have access to?
Dr. Mark Box:
I think in the beginning you're probably not, in this next year, 2023, going to see a big difference. Humira will probably still be the... If you're on that TNF inhibitor, that's probably still what you will get. In the beginning, when that first biosimilar comes along, it may be new starts. So, that will be your new start from the beginning, but I don't think people established in most cases will be forced to change. As time goes along, we may find that what your insurance company requires, in order to maintain that product, is a different brand of it.
I think people should try to be reassured that these drugs are high quality. They are highly similar. The likelihood of them not doing exactly the same thing is infinitesimally low. I wouldn't anticipate, changing from the originator to the biosimilar, that you'll have any difference because really, in those people who are blinded to this process, they don't have any difference. European countries have, and in many cases on a yearly basis, changed what drug is available to their population and not seen adverse reactions.
I think you have to be reassured that there is a quality system here that is outside of any politics or anything else that we worry about that has really reassured that these drugs are available. This is an evolutionary process that has been going on for a decade.
Rebecca Gillett:
From the Arthritis Foundation's perspective, we do hold a position. If you want to read our position statement on our website, at arthritis.org/biosimilars, you can find the full statement. Basically, our position is that these drugs are equally effective and safe, but we are ultimately patient advocates, and we are here to support you and advocate for you. It should be up to you and your doctor if you want to switch, especially if you are in a remission or your disease is stable.
Just have this conversation with your doctor, so you know. Then, call your insurance and find out: “Do you have plans for any changes on your formulary of what you’re covering and how you’re covering?” Just make sure you take the lead. You hold the ball in your court when it comes to advocating for yourself.
For me personally, it's comforting to know that it's been used in the European countries for many years. I know patients who are excited about the promise of lower costs because I know there are patients out there who haven't even had access to biologics and will want to make a switch. How do they start that process? How should they approach that with their doctor?
Dr. Mark Box:
Well, again, so much of this in our country is dictated by what the insurance formulary says. And so, if you're a Medicare patient with IV medications, in those cases there is more of a choice of using a biosimilar versus using the originator product.
With commercial insurances, usually when we send in for an approval for, say, Remicade, they may come back to us and say, "In order to get access to Remicade, you must fail X, Y and Z," which are usually one or two of the biosimilars. Sometimes there is no way around that. It's like, "You will not get anything if you don't do these, period."
I think as new starts are coming along, that's where we really will see the opportunity to let people start with a new product. I have no idea, starting January 1 st, whether Amgen's Humira biosimilar is going to be available on any given insurance plan. We'll have to see, when we start sending in requests for prior authorization, what comes out.
Rick Phillips:
I use rituximab, and I have asked the last two times if the biosimilar's available and if it could be used. Because I'm very excited about the prospect. So far, I've not been able to get it, but I know it's coming, and I am very excited about it.
Dr. Mark Box:
It's interesting that infliximab's been a biosimilar for maybe five years, rituximab only for about year or so. But now we are seeing that when we have new starts, they are demanding Truxima or Ruxience, which are two of the biosimilars for that being the starting product for patients. They are available, and for Medicare patients that would be an option to discuss.
Another issue here is inventory management and control, because it's going to be hard to try to keep, for the IV world, too many different products in your refrigerator for this patient and that patient, depending on what the demands of their insurance are for products.
We've actually gone a couple of times and said, “OK, we'll happily use a biosimilar for your patients, but this is the biosimilar we’ve got in the refrigerator, and this is the one we’re going to stock. Will you let us use it?” We've usually won those cases with them. We still have gone to using a biosimilar, but we haven't used their preferred biosimilar.
Step therapy will apply to biosimilars in a way. Because now what we are seeing with the infliximab infusions are that they are requiring that, in order for you to get the originator product, that being Remicade, you have to have failed one or two of the available biosimilars in order to get that originator product. That's a different form of step therapy, but it is there.
Rebecca Gillett:
I do want to define step therapy for those that don't know what it is. And that is a practice of being told to fail first. So, whatever drug your doctor prescribes you, you're expected to fail that drug first before insurance will cover the drug that the doctor has prescribed for you. Basically, insurance is somewhat dictating what medication you're doing. That is something that we have been successful at the Foundation in advocating for in many states across the U.S. and have been working hard for many, many years to try to get a national bill supported for limiting that practice.
Dr. Mark Box:
That is something that is a big area of advocacy both in the Arthritis Foundation and the Coalition of State Rheumatology Organizations and the American College of Rheumatology — to try to stop this capricious process of step therapy.
Rebecca Gillett:
If somebody ends up taking a biosimilar, are there any side effects they can expect to experience? Are they the same kind of side effects from the reference biologic?
Dr. Mark Box:
Here's the only thing that right now I could say that may be a difference: Several years ago, both Enbrel and Humira, which are the TNF inhibitors that are Sub-Q injectables, changed their formulas so that they took out what was causing them to sting…
Rebecca Gillett:
Citrate-free…
Dr. Mark Box:
Yeah, citrate-free, or phosphate-free with Enbrel, and so that did make a difference. People found them to be much more comfortable. I don't know at this point in time with these biosimilars how well they're going to do. I would really assume the first one from Amgen, who's done this with their Enbrel already, by taking out the thing that caused the burning discomfort, that they will probably do the same thing.
I think the only difference you may feel is if the buffer that's used with it is not citrate-free, that there could be some burning again. That may be a good reason. I mean, that would obviously be a reason to say, "I can't take this," and we go back. OK, but you've tried what it is.
I don't believe that you will have a difference in how well that drug works for you. You should have no more likelihood of an allergic-type reaction to this one, because it is the same molecule. It's a humanized molecule. It should not in any pharmacological or medical sense cause you to be more likely to have any problem with it than the originator product.
I think they all will know that if they want their product to be successful on the market, it has to be citrate-free, and they have to have a friendly type of pen, and it may be even better.
Also in our system, the copay cards are very, very important. Big companies are going to come out with the same type of copay cards, the same type of patient assistance programs that are important to the affordability for the individual of these medications. I suspect that five years from now, we will see the price of Humira drop by probably 50 to 75%. There will be a bottom point of which it can't drop any lower because manufacturing of these is way too expensive for it to go down to what we would think of as oral generic drugs. But it will be less.
Rebecca Gillett:
Well, that's the good news, right? Easier on the pocket for the patient, which it's always not easy, because there's a lot of medications and copays to pay for. It does ease some of that financial burden on the system as it were, as you said, especially the patient.
PROMO:
Whenever you need help, the Arthritis Foundation’s Helpline is here for you, now offering support in Spanish and other languages. Whether it’s about insurance coverage, a provider you need help from or something else, get in touch with us by phone, toll-free, at 800-283-7800. Or send us a message at https://www.arthritis.org/helpline .
Rebecca Gillett:
I'm going to move to our listener segment. We posed a question on social media to hear from our listeners about biosimilars and if they even knew what they were. We asked: "What do you know about biosimilars to treat autoimmune inflammatory arthritis? What are your concerns?" One person just mentioned that insurance isn't covering it yet, and then somebody did ask, "Are they injections or pills?"
Dr. Mark Box:
To use the term "biosimilar," it must be a biologic product. All biologic products have to be injected or infused. There will never be a true generic of any of these injectable or infusible drugs. They will always be considered to be biosimilars because they have to be made in living organism tissues.
Rebecca Gillett:
Well, that answers that question. But it also brings up another point, though: If it is an injectable or an infusion, the biosimilar version of it would be an injectable or an infusion?
Dr. Mark Box:
Yes. If they're going to call it infliximab YYCA, then it has to be administered in the same dosings in the same way as the originator product. If you look at the package label, the dose range, the dose interval, are exactly the same as the originator, and the same thing will be for Humira and their biosimilar. It will be a subcutaneous injection of 40 milligrams every two weeks. Can be accelerated to weekly with certain diseases or certain processes. There would be no other difference.
Rebecca Gillett:
On Instagram, we asked, “What is your biggest concern about being switched to a biosimilar?” Somebody mentioned paying for it and insurance authorization and dealing with specialty pharmacies. That whole process is probably going to be the same?
Dr. Mark Box:
It's going to be exactly the same. Some of it in the beginning will be driven through the doctor's office. When we try to get an authorization, or we try to get your renewal, your insurance company's going to come back and say, "This is our preferred product in this category. Have they failed this one?" That's where it's going to come from in the beginning, as I see it.
Now, as we get more comfortable with these, we may choose, as physicians, to say: “You're a new start. We're going to use this biosimilar as your new start, mainly because I know your insurance company will approve it.”
Rebecca Gillett:
OK. Somebody does mention they're concerned about starting a new one, seeing potential with it, and then insurance pulling out from under them and “having me change because of the cost.” What do you think about that?
Dr. Mark Box:
That's something that probably will be realistic. But again, I think you need to be reassured that you are getting a 99 and 9/10% similar product. Hopefully, as these become less expensive, you're going to be less likely to have the whole class pulled out from underneath you than anything else.
Rebecca Gillett:
EGoldstein7 mentions: developing antibodies again.
Dr. Mark Box:
Anti-drug antibodies is something that happens because, these at best — even when they're humanized and made so that your body won't recognize them as foreign — they are foreign. You're injecting something foreign, and our body's normal response to foreign substances, coming in like viruses or a splinter, is to have an immune reaction to them.
Originally, there was this concern, with infliximab products, that if you had to change them too often, even those subtle differences might lead to you forming antibodies against it. The studies have not supported that. And with the adalimumab/Humira products that are out there… there are, I think, seven of them right now FDA-approved.
Only one of them will be marketed in the first six months.
But of those approved products, two of them are actually considered interchangeable. They did studies where they switched people back and forth multiple times during the period of a year, between the originator and the biosimilar, and didn't see antibody formation. So, they were allowed to say that their product is truly interchangeable.
Now when we're sending something to a pharmacy for Humira, once these two interchangeable products are there, the pharmacist will be allowed under law to dispense whatever is the least expensive product on his shelf to you. I don't have to purposely write that, “Your Humira.” Unless I've written “do not substitute” on the Humira prescription, that will be allowed. Just like right now: I write for Lipitor. It's very doubtful you're going to get brand name Lipitor; you're going to get a generic that's on the shelf in the pharmacy.
However, one thing to note is that laws exist in all states saying notification must be given to the doctor and the patient, within three days, that what has been dispensed is the biosimilar instead of the originator product. That will not happen immediately, because those products that are interchangeable are not the ones that are going to be on the market for the first six months. But they will come. And so, we will see more of that ability of the pharmacy to substitute immediately or from the beginning, the products. That is because they have done the studies to show that there isn't any reaction…
Rebecca Gillett:
Right, through the patients. You just introduced an important term that we're not going to really get into a lot of detail on this podcast, but “interchangeable.” Just as you said, those interchangeable biosimilars aren't even going to be out yet in the first six months of the new year. You'll have to check out our website at arthritis.org/webinars. We did a webinar on biosimilars and covered the topic of interchangeables, so look there for more information.
Dr. Box, as we head into the new year and people are anxious maybe about biologics and biosimilars, please share your top three takeaways from today's conversation.
Dr. Mark Box:
These are products that are proven by our FDA to be highly similar with no meaningful difference in their safety, efficacy or potency. That we have to look at these as cost savings to our system and potentially, eventually, to the individual, in terms of being able to maintain these medications. And that the experience out there with these products, which have been back for nearly a decade in some areas, has shown that they’re equally efficacious and that there are no increased number of side effects associated with these medications across large populations.
Rebecca Gillett:
Thank you, Dr. Box. Rick, do you have anything that you want to share?
Rick Phillips:
My top three takeaways… Biosimilars are coming, and that's number one. Number two: It should usher in a new era of affordability, which should broaden access to these very important medications. Number three: I believe it will increase research and development into further advancing this pipeline. I think it will do that because the companies who are currently producing them at a very high cost will want to press forward in order to get the next level of medication, and more competitors is always good.
Rebecca Gillett:
Yeah, you know, bottom line for us as patients is having the better treatments and access to them. And having access for more people to be able to take these drugs is super important. Thank you, Rick.
Go to our website at arthritis.org/biosimilars to find more information and read that position statement from the Arthritis Foundation. Also, I just want to say any information that you have, or you run into any issues, don't forget you can contact the Arthritis Foundation's Helpline. Thank you so much for joining us, Dr. Box. We appreciate it.
Dr. Mark Box:
Thank you.
Rick Phillips:
Thank you.
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