Dr Syal reviews his presentation at the virtual AIBD Regionals meeting on April 30 about new and upcoming information on biosimilars for inflammatory bowel disease.

Gaurav Syal, MD, is an Assistant Professor of Medicine at Cedars-Sinai Medical Center, Los Angeles. 

TRANSCRIPT

Gaurav Syal, MD:
Hi, my name is Gaurav Syal. I am an assistant professor of medicine, a gastroenterologist focused on inflammatory bowel disease at Cedars-Sinai Medical Center in Los Angeles, California. I'm going to talk about a few important points from my talk from earlier today on what's new in biosimilars in inflammatory bowel disease. A lot of us have heard about biosimilars. We've had our reservation about biosimilars, et cetera, but now we have emerging data about their safety effectiveness, et cetera. So I reviewed the FDA approval pathway of biosimilars in the US and I think there are a couple of important points to highlight there. So the biosimilars do not have to go through the long process of doing these large studies phase three clinical trials, and then being evaluated by the FDA about the safety and effectiveness. And generally this standard period for a new medicine takes several years.

Now, FDA has devised an abbreviated pathway for approval of biosimilars because by definition biosimilars are highly similar to the originator product. So there are no meaningful differences in the safety and in effectiveness of a biosimilar compared to the originator product so that's what the biosimilars are. And because they highly similar and there is already existing data from the originator product about safety and effectiveness, the biosimilar manufacturer does not have to go through the same long process. What the FDA wants is studies to analyze the product to make sure the product is highly similar as I said, and there are no meaningful differences that could impact its effectiveness and safety. There are some subtle differences that are acceptable, but those differences should not impact again safety and effectiveness. So once the manufacturer has proven that, then they generally would have to do some study, at least one study, or a couple of studies in one or more of the indications where the originator product is already approved for.

For example, if a product is approved for rheumatoid arthritis, ulcerative colitis, Crohn's disease, spondyloarthritis, the manufacturer of the biosimilar could choose one or two of these indications and boost clinical studies and those to prove that the biosimilar is not inferior to the originator product and the safety is similar. And once they have done that, then FDA allows a concept of extrapolation. So even if the biosimilar manufacturer does study only in rheumatoid arthritis, and they prove that the biosimilar is similar in efficacy and safety, then the FDA will approve it for all the indications where that originator product is already approved for and that's how the process has been abbreviated by the FDA. So that's important to understand that we may not see studies for every biosimilar in inflammatory bowel disease before they're approved for inflammatory bowels. Traditionally, most of the studies have been done in RA or enclosing spondylitis or psoriasis before the biosimilars are approved.

There is another important concept regarding biosimilars, which is interchangeability. So when the biosimilar manufacturer does what I've already mentioned, they prove biosimilarity. So proof of biosimilarity is what we've talked about, FDA approves it for all the indications that the originator product is approved for. Now, interchangeability is a different concept. Interchangeability, it requires not only the proof of biosimilarity, but it also requires additional proof to basically show that if there are multiple switches, if the medicine, originator product, and the biosimilars are switched back and forth in a one patient and a particular patient, then that patient should not have any compromise in the effectiveness of the medicine or the safety of medicine. So there is an additional requirement that usually is met by doing these multiple switch studies.

If the biosimilar manufacturer is able to do a multiple switch study and prove that the biosimilar is equivalent and safety and effectiveness to the originator product, then the FDA will give them the interchangeable status. Interchangeable status means that when you prescribe a medicine, an originator product let's say, and the pharmacist who actually receives the prescription has the ability to change it without requiring your approval to that biosimilar, to the interchangeable biosimilar, so they can be changed at the pharmacy level without requiring provider intervention. The only caveat is that this is subject to state pharmacy laws, so some states may allow that some states may have some other important factors that will have to be met for the pharmacists to be able to do that on their level, so this is another important concept.

So now coming onto the evidence about biosimilars, we have all heard about the studies which introduced biosimilars in the arena of IBD. Now the research has advanced further in reassuring us that biosimilars are truly safe and effective, so there are multiple biosimilars where the studies have been done exclusively in IBD and they have shown to be effective. There are also studies which have been done with single switches, which means either from an originator product to a biosimilar or one biosimilar to another, or from a biosimilar to the originator product and they all have shown that it is a safe practice to do these things. There has been a concern about multiple switches, which very likely in a clinical practice, that the patient may end up having to switch multiple times back and forth between these different originative product and biosimilars. And is that safe and effective?

And there are some studies, they're observational studies, so in scientific terms, we will say this is still low quality data, but a lot of these studies now have show own that it is again safe to do that. One important point, I want to highlight that we will also be seeing some interchangeable biosimilars in the near future. There has been one interchangeable biosimilar for adalimumab that was approved very recently by FDA and so we will be seeing that coming on in the market, along with a many other biosimilars for adalimumab in the next year in 2023, once the patent runs out. There are already in many infliximab biosimilars, which are out there in the market and being used.

The last point I want to highlight about is the placebo effect. So a placebo effect is an important consideration when we talk about biosimilars. Patients have concerns when they hear that their insurance wants to switch them from the originator product to a biosimilar that they've never heard of. And rightly so, they might feel that they're losing control of their disease, their disease is going to flare, they're going to have some side effects. And placebo effect basically refers to the patient's perception influencing what they feel about effectiveness or safety of the medication, so it's the opposite of placebo effects of, so placebo effect is without receiving any drug, some patients might get better. This is the opposite, even though the patients are receiving the actual drug biosimilar in this case, but because they have reservations about the biosimilar, they may perceive the biosimilar to be less effective or causing side effects where it truly might not be the case.

So how can we minimize placebo effect? The placebo effect in fact can lead to increased drug discontinuation because the patient doesn't feel it's effective, or they feel they're having side effects, et cetera, so patients may not want to stay on their medicine. The way we can minimize placebo effect is with patient education. So I think when in this era where we're seeing more and more biosimilars in the market, I think we should talk to the patients about what a biosimilar means. Definitely when there is a question about them being switched from the original product to the biosimilar before it actually happens for non-changeable biosimilars, the provider usually is informed that X, Y, Z third party pair wants to switch your patient from originator product to a biosimilar.

So that gives us an opportunity to actually talk to the patient, reassure them that these are highly similar products with no meaningful differences in safety effectiveness, and even antibody risk. And there are also a few studies, which I've shown that when you educate the patients, the patients actually have a positive perception about the medicine and they're more likely to stay on it, they're more likely to not experience any change in the effectiveness or perceive that they are having any additional side effects. So I think addressing placebo effect is key in the era of biosimilars. That is all, thank you for your attention.