Part 2: Nabeel Khan, MD, Discusses the Significance of a VA Study on Biosimilar Switching

To watch part 1 of this interview, click here.

The Center for Biosimilars® (CfB): I’m Tony Hagen, senior editor with The Center for Biosimilars®. Today, we’re talking with Nabeel Khan, MD, an associate professor of clinical medicine with the University of Pennsylvania, and an author of a retrospective, real-world study that demonstrated safety and efficacy for patients with inflammatory bowel disease [IBD]. They switched from reference infliximab to the biosimilar Renflexis, or from biosimilar Inflectra to Renflexis. The findings showed a high rate of continuation for patients on Renflexis. Findings from the study were presented at the American College of Gastroenterology 2020 Annual Scientific Meeting.

Let's get into the topic of double switching. For this study, you were able to evaluate both patients who were on reference infliximab [Remicade] and those who were on a biosimilar infliximab [Inflectra] who switched to biosimilar Renflexis. This enabled you to study switching from 2 sides. How has that been an advantage?

Khan:I think this double switching has been a very important issue that we wanted to look at because of the fact that each time a new molecule is introduced, there is a question of whether there is immunogenicity and whether there is any antibody formation. That is a very important question, especially for the future, when you may need to switch again or something else may happen. So, this was a unique feature [of the study]; we had a significant number of patients who underwent a double switch in a relatively short time period.

Mechanistically and at the molecular level, we wanted to see whether there was an increased risk of failure with a double switch versus a single switch, based on the fact that these are all protein molecules and they have the propensity to have some development of antibodies against them. That was an inherently important question for us to answer. We were able to look at that in this particular study because we had a relatively high number of patients who had a double switch versus a single switch. And we found that there was really not much of a difference.

We haven't done the full statistical analysis on it yet. There is no P value that we can show right now, but we have the initial results and we are expecting the manuscript to be out very soon. We are going to submit the manuscript for publication, and there will be more detail on this. But in the preliminary analysis, we did not find much of a difference between doing single or double switches.

The value of knowing how patients will or will not progress on a biosimilar and then on another biosimilar is important because the pricing might be different. In the private sector, for example, you might find it attractive as a clinician or a patient to switch to a cheaper form of a biosimilar. And you would want to know that if the patient has received one molecule or another, that switching will be OK.

Multiple studies have shown that there has been a delay in biologic usage. Perhaps one reason for the delay is the cost aspect. [Garbled].

So, hopefully, by showing that these cheaper drugs are safe to use, there can be greater utilization of them and more people on biologics, which has shown to have an impact on disease over the past 20 years of use. The best efficacy always occurs when you use [the drug] early in the disease. If you use it earlier, within the first few years of the disease, that is always much better. So, the aim is to, obviously, increase the utilization of these drugs and show that there can be some cost savings along with safety for the patient. Reduced cost may lead to better utilization of that drug.

CfB: Tell us about the continuation rate findings and the significance of these. Is the 83% continuation rate a very strong number?

Khan:Yes, 83%, I agree, is a very relatively strong number. A lot of these patients were stable when we started off. And that was a clinical question that we really wanted to answer. If you look at the NOR-SWITCH study, it was somewhere between 26% and 31%, but, again, those are people who started on therapy.

So, there are different numbers out there. It's not an exact science. And obviously, all the patients were not controlled. We looked at everybody. We did not look at a [group] based upon their [past medications]. Our criteria were that they had to be stable. It was not that they had 3 or 4 drugs before they were stable. There are multiple different parameters that can impact your stability.

But if you look at all data across the board, this compares very favorably: 83% or so were still on the drug at the end of a year. So, I think that is about the best data you will get by looking at this particular subgroup, which is chronic disease, which has its ups and downs and has a different avenue of disease course [than other conditions]. CfB: Can you discuss the reasons discontinuations occurred, and do you have any thoughts or conclusions that you drew from these data?

Khan:So, they're pretty spread out. People were spread out across the board: They developed antibodies, had a chemical relapse, had a hypersensitivity reaction, which was also small. Some developed cancer over that time period, which obviously can happen; they developed infection. Patients sometimes refused to continue treatment any further.

So, it was scattered, but nothing really stood out. We could see that there was not a particular reason for stopping treatment. There was a smattering of different reasons for discontinuation across the board, including infectious malignancies, lack of clinical response, which we expected. So, if you take out the lack of clinical responses, it was about 8% to 10% on that basis. It was a whole smattering of different reasons. There was no particular signal that emerged, when we looked at the reasons for discontinuation.

CfB: Do you think you could have performed the same study in a private clinic or a commercial insurance setting?

Khan:I don't think that would have had the same level of granular data. We had all the colonoscopy reports. We had the the follow ups and the clinical visits. We could look into each time they came into the clinic for an infusion. We looked at the factors that were recorded and all the individual notes.

It would be a very massive undertaking if, for example, 30 big institutions decided to get together, looked at all the records, and decided they wanted to do this kind of study. They could probably do that but that would require collaboration from multiple different investigators from multiple different institutions who could then collect all the data. So, the answer to your question is yes, but it's very cumbersome to do. It would require a lot of effort, as well as coordination, in order to achieve this, but it could be done.

CfB: What are the further implications from your findings for the medical community? What may people infer from this study that we haven’t already talked about that might be of value for treating patients in this setting?

Khan:What we have seen is that—and again, this is one of many other studies, just to put that into context—we are getting more data on switching. The amount of money that is available in health care is limited. I think we all have to look at that aspect. But if there is a drug, the most important thing is that it should be safe and effective, and that is what we're looking at. If there is a drug that is safe, effective, and a lot cheaper, then we should offer it as an alternative to our patients so that we can increase the utilization of this drug. Obviously, if it is much cheaper, then there's money to be saved. That's a call that should be made, saving health care money, but without compromising efficacy and safety.

That is why the VA has always been very patient centric, as well as physician centric. And that is why there's always a voluntary decision whether you want to make the change, or not. And what we're hopefully showing is that our aim is to help patients and physicians decide if they want to make the change or not. That is what the real-world data are about, to give some real-world experience so that patients and physicians can see what the data are, and that can help them make the decision one way or the other.

CfB: Just as a closing thought. The second study publicized by Samsung Bioepis noted a huge, 800-fold increase in the use of biosimilars in the VA. That's quite something. What might account for this level of confidence within the VA versus outside.

I'm not familiar with what the numbers are on the outside so, I can't really make a comparison. You have to look at what the starting point is and how many patients were on [the drug]. I don't think the VA is very different from the private sector, on that basis.

I just want to just clarify that the findings from the VA are generalizable to the private sector also. I want to make that very strong point. VA patients are very much the same as those in the private sector. In fact, they have a little bit greater access to care and medications because they don't have to pay anything for the medications. All of their infusions and everything else is free. So, that, I think, is one aspect. I've been in the VA for 10 years and I have never had [a problem] writing a prescription for a biologic or biosimilar infusion. I also worked in the private sector, and in the private sector, sometimes the insurance agencies will refuse to [approve] something. So, the VA is definitely not worse and maybe better than what it is in the private sector.