The Center for Biosimilars® (CfB):I'm Tony Hagen, senior editor for The Center for Biosimilars®. Today, we're talking with Jorge Garcia, assistant vice president of the Oncology Service Line at Baptist Health South Florida and also a member of the Association of Community Cancer Centers' Board of Trustees. Garcia explained how Baptist Health gave pharmacists latitude to issue biosimilars to patients to reduce administrative complications and save money. He also discussed strategies used by innovator companies to keep biosimilars off the market and the effect this is having on patient access.

Reimbursement is a significant barrier [for biosimilars]. At Baptist Health, you've managed to increase biosimilar use by putting the pharmacy in charge. Can you describe how you achieved that and what you learned from this experience?

Absolutely. So, I think for a successful biosimilar implementation, one of the key components is that for every patient and every administration, you have to [check] out the benefits. And we do that, again, for every patient on every administration, because the patient's benefits could change throughout the course of the therapy. We see that a lot with Medicaid patients and older patients that have life changing events and other things of that nature.

So, prior to our new process, our authorization team would go ahead and get an authorization for whatever the doctor was prescribing, and when they were not successful getting an authorization, they would have to contact the provider again and have them write for a different product based on what that health plan required. And that process was convoluted. The physicians, sometimes, would not get that message on time, or it would take them some time to update the system to the new orders. And this would be, obviously, frustrating to the authorization team and very stressful as the date of treatment got closer and closer and we still didn't have the right orders for that patient.

What we did to eliminate that is we, today, follow a facility preference approach where when we review biosimilars in P&T [pharmacy and therapeutics committees], we provide our authorization team with our facility preferred products. So, regardless of what the prescriber prescribes, our authorization team will always try to get an authorization for our preferred product. And if they're not successful getting an authorization for our preferred product, then they tailor to whatever the health plan provides. And they document that in the EMR [electronic medical record]. When our pharmacists are verifying that product under the product dispensation, we see the notes from the authorization team, saying specifically which product the health plan approved, and our pharmacists are able to independently switch to the product that the patient has benefits for.

What that did in turn is it eliminated the providers from being a part of that workflow. We do have an automatic substitution policy that we had in place way before biosimilars existed. And we just added our biosimilars to that policy. And of course, we have provided input about what goes into that our substitution policy that basically allows us to independently make those changes without having to consult with the providers every single time.

This has been a huge satisfier for the providers, because what they want is for the patients to get the drug. They know that a lot of this is heavily payer dictated and they don't want to be involved in the logistical piece of it. All they want to know is that their patient is going to get the drug that they intended. Our authorization team is also not having to constantly be contacting the providers to have things changed. So, this has really been a best practice that has been transformational in our ability to manage the day-to-day, where we leave very little room for error there, because we do that benefits investigation on a dose-by-dose basis, obviously, patient-by-patient.

CfB: So, a doctor will not prescribe by brand; he or she will prescribe by the generic name of the product, say trastuzumab or bevacizumab. And your team will decide on whether you can get preauthorization for the biosimilar that goes by that name or whether you have to use a brand product or something else, is that correct?

That is exactly correct. And if, in any way, the provider wants to keep the brand names, they have the ability to write ”medically necessary,” just like we would write in a prescription. But we don't see that very often at all.

CfB: To make a system like this work in harmony, you need to overcome certain complexities. You may need to educate all the stakeholders in your institution. Can you describe how you accomplished this and how you smoothed the way for a process like this?

Absolutely. I think when we think about a biosimilar implementation, a few stakeholders come to mind. Obviously, the pharmacy, nursing, and the providers. But there's more. There are the IT [information technology] teams. Typically, those IT teams have a long agenda of priorities, so the biosimilar agenda has to fit into those. They’re an important stakeholder to keep in mind. Also, with the type of capabilities that they can provide to support this process, I mentioned that we moved our program to document it in our EMR and that required a simple interface that IT was able to do for us. And we also have drop-down options for multiple products, and you just have to work with your IT team to understand what kind of capabilities they can lend to you to make this process successful.

But it also requires including the registration team for some products, like pegfilgrastim. What product you choose dictates whether the patient is going to get treatment that day or the day after. So, [the registration department] has to understand that to be able to register patients appropriately. And then, the business office, the authorization team, and others. In my experience, those clusters of teams can vary within one organization. So, I will have to meet with a group of folks if I do a biosimilar implementation in an outpatient facility. If I am doing the same biosimilar implementation in an inpatient facility, there is a different nursing team, a different pharmacy team, and a different authorization team. So, you have those clusters of teams that are going to work closest to that site of care to be able to have it be successful.

CfB: We've discussed the pegfilgrastim differentiation and how an innovative product can take market share away from biosimilars, just as Neulasta Onpro has done. Patent thickets around adalimumab [Humira], have prevented biosimilars from reaching the US market. How are these things affecting the success and the sustainability of the biosimilar market?

Yeah, there's so much that goes into this. And I really appreciate this question. But I think the important thing to recognize is that biosimilar companies take a lot of risk when they decide to pursue a biosimilar. We know that there is no patent protection for biosimilars. So, you could have any number of players in that market when you decide to pursue biosimilar adalimumab. You know that many other companies may develop a biosimilar and they will play in that space. You’re never guaranteed a market share of that, if at all. We need to recognize that component.

In the space of adalimumab specifically, we know this is the one biologic with the highest cost at a global scale. Here in our country, we see that that product has lifted the entire patent exclusivity period. And we still cannot pursue biosimilar options due to patent litigations and other things until 2023. That's concerning. We know, per the FDA website, if we go today, we know that there are several adalimumab biosimilar programs that have been completed and approved. And those companies are standing by until 2023 to be able to give us a biosimilar option.

And again, I think, in our industry, we all understand the full patent exclusivity period and how necessary that is to support innovation and innovative companies. That's not the argument here. The concern is more so that once those products have gone through the entire path and exclusivity period, how many more years in addition to that do we provide exclusive market access? That's a concern. I think it is less of a concern in other countries that have completely different patent protection laws, and I think that is why Europe has been so successful and we have seen a lot more market penetration of biosimilars in general.

One other point to make here, specifically in the case of adalimumab and specifically as it relates to the level of risk that pharmaceutical companies have when they pursue biosimilars, is that by 2023 when biosimilars for adalimumab may be able to enter the market, the standard of care may be something different. AbbVie [Humira's manufacturer] itself has a couple of new products that are demonstrating better outcomes. And so, when we get to 2023, again, the standard of care may no longer be adalimumab or the biosimilar version of that, but it may be something else. However, these companies have already invested a ton of resources to get their product studied and approved. So, again, lots of risks are involved when it comes to pursuing a biosimilar.

CfB: A recent report by Amgen was very positive on the health of the biosimilar market, and they described rising market share in a number of the 7 different basic drug categories for which biosimilars have been approved. But then if you talk to other people, such as consultants and so forth who are trying to open up those corridors to biosimilar access, they are very discouraged. And they say that the market is not very healthy at all. Depending on who you speak to, it's a great market or it's a very sour market.

Absolutely, and what we see is that a number of biosimilar development programs have actually been dropped by multiple companies. Obviously, companies try to have their intel on this, and they assess, through the development period, if it's still worth the risk that they are taking based on the evolving market. In the case of adalimumab, like I talked about before, clinicaltrials.gov is listing a number of studies just trying to assess outcomes with adalimumab compared to all other options. So, depending on where those studies go, again, by 2023, the recommendations may be very different from what they are today.

CfB: Yeah. And, of course, if the recommendations for your products aren’t good, this could be devastating for these 9 companies that are lined up to bring adalimumab products to the market.

CfB: And caught in the middle of this issue are the patients. They'd like cheaper medication, but they've got to wait, in case of adalimumab, wait until 2023 to get a cheaper product. So, alongside access to lower-cost products goes affordability. So, you cannot expand the number of patients being treated if you can’t lower the price. Can you discuss these issues?

Absolutely. So, a couple of angles that we could take with that question there. I think, especially looking at European models, when you have access to products at a lower cost, you can get more units of that product to make available to more patients. And so, with biosimilars you do look at increased access. It is believed that that access is going to translate into better outcomes. We have ongoing studies trying to paint the full picture there. I think again, Europe is a little bit more advanced that than we are with that regard.

But in models, when we think of the patient out-of-pocket [costs] we think of the typical insured patient, but the reality is that we have patients that are underinsured or completely uninsured. In our geographical area of South Florida, we have patients that are self-pay and we have patients that are international patients [who have to] cover a lot of those expenses directly. So, this means different things to many of those patients' categories. But to your point, in the case of adalimumab, they're not having a biosimilar option at a fraction of the cost the way that they do for other biologics that there is a biosimilar available for.

And I really think, from a provider standpoint, our goal is to make sure that we have a parity approach, so that we present that provider and that patient with options, and based on their situation, they can decide financially what is the best choice. And we do see in our experience that patients are highly sensitive to their financial responsibility, even when it may come down to just their out-of-pocket responsibility. So, when you have that discussion with the patient, and you educate them, in our experience, we see a lot of patients favor biosimilar options.

In our practice, we have a class—a chemotherapy biotherapy class—that every patient must undergo before they begin treatment. We talk to them about biosimilars. I cannot give you any examples of a single patient that have reached out and said, "I am not comfortable with the biosimilar options," and we've had hundreds and hundreds of patients.

So, again, I think patients as stakeholders in understanding the clinical part of the discussion, which is done by a nurse navigator, and the financial part, the out-of-pocket with our financial navigators, tend to be very supportive of biosimilars. But we have to be able to present them with that opportunity. And that's what it boils down to. Sometimes due to a payer restriction, we cannot present them with a biosimilar opportunity or some other times due to just no access in the marketplace, like in the case of adalimumab. Patients are not able to drive that benefit today.

CfB: Providers are often concerned about using biosimilars and they prefer to look at clinical data rather than the type of evidence that the FDA relies upon for biosimilar approval. Can you discuss this issue here? Why can't doctors be persuaded on pharmacokinetics and other types of evidence rather than going for comparative data, which is not considered all that reliable?

Yeah, but I think we have to really look at the approval process for biosimilars, which is not to reestablish the safety and efficacy of the compound because that has already been done by the innovator company. The goal is really to demonstrate biosimilarity and or interchangeability. And so, we do rely heavily on analytical studies. But we also do clinical studies for pharmacokinetics [PK], pharmacodynamics [PD], and immunogenicity. And I think that's [where there are] misconceptions. I think some believe that there are no clinical studies at all. But we know that that PK, PD, and immunogenicity studies are there to support every FDA approval.

I think the other component to keep in mind is that if those studies do not yield sufficient evidence, that pathway definitely does call for a phase 3 clinical trial; in this case, it will be more so a confirmatory trial to just try to resolve remaining uncertainty.

Now, the way things have been going here in the US, the FDA has been able to gather enough evidence just by having the PK ,PD, and immunogenicity studies and not requiring those phase 3 studies. But we are seeing that some companies are taking the initiative to have more of a phase 3 type of study design, or, we have not seen it yet, but again, the FDA can request that study if they deem that necessary.

I think what we have to keep in mind here is that balance. The goal of biosimilars is to try to bring product options to the market at the lowest feasible cost. And if we have very robust confirmatory trials, that can get very, very expensive. We already talked here about how there is no path and exclusivity for biosimilar companies. So, they will be doing all of these trials pretty much like the innovator companies did to bring their product into the market with no guarantee of product utilization because there's no patent exclusivity. So, the model itself is not sustainable by just having multiple companies do all of these studies at the phase 3 level.

We followed a different approach looking at most sensitive patient populations and looking at extrapolation and other methodologies, to, again, show that there is biosimilarity. The safety and efficacy of the compound has already been proven.

And I guess, just to close with this question, today, we do have 5 years of pharmacovigilance of biosimilars being exposed to large patient populations in things like extrapolated indications or patients that were interchanged because their insurance required them to change between products. And so far, we are not seeing any indications to pharmacovigilance that there is any clinically meaningful difference in terms of safety or efficacy. Furthermore, beyond the use of biosimilars in our country, we know Europe has another 6 years on top of our 5 years of experience. And in both of these 2 markets that I follow closely, we have not seen any incidents of any biosimilar that have been removed from the market due to a safety or efficacy concern.

Videos

Jorge Garcia, PharmD, MS, MHA, MBA, assistant vice president of the System Oncology Pharmacy Service Line at Baptist Health South Florida, discussed how Baptist Health increases biosimilar use and how innovator companies fight to avoid biosimilar competition.

Part 2: Jorge Garcia on Giving Pharmacists Latitude to Switch to Biosimilars

Hi, I’m Skylar Jeremias for The Center for Biosimilars®, your resource for clinical, regulatory, business, and policy news in the rapidly changing world of biosimilars.

The American College of Rheumatology’s (ACR) Convergence 2020 was the annual meeting of the ACR. This year, due to the pandemic, the meeting was hosted virtually from November 5 to 9. During the conference, a number of study findings were presented on biosimilars used to treat rheumatic diseases. Here are the top 5 biosimilar articles from ACR Convergence 2020.

Number 5: One study of multiple biosimilar switches for patients with a variety of rheumatic musculoskeletal diseases demonstrated a 

 and no major changes in disease activity or function.

Number 4: In a study of the use of infliximab biosimilars among patients with gastrointestinal and rheumatologic conditions, investigators found 

Number 3: Investigators presented evidence of what they say are 

 of a multibiomarker disease activity score in patients with rheumatoid arthritis.

, including one on application methods for Celltrion’s adalimumab biosimilar candidate (CT-P17), were reported at the ACR Convergence 2020.

 at the meeting shed light on performance of Pfizer’s and Celltrion’s versions of adalimumab biosimilars.

To read all of these articles and more, visit 

Here are the top 5 biosimilar articles from the American College of Rheumatology (ACR) Convergence 2020.

The Top 5 Articles from ACR Convergence 2020

Here are the top 5 biosimilar articles for the week of November 16, 2020.

 to bring 5 biosimilars to treat oncology and autoimmune diseases to South Africa.

Number 4: US rheumatologists who prescribe tumor necrosis factor (TNF) inhibitors are familiar with biosimilars; however, there is broad awareness only of infliximab biosimilars, according to 

Number 3: The International Generic and Biosimilar Medicines Association (IGBA) has 

 Global Biosimilars Week, an attempt to build momentum for the use of biosimilars.

Number 2: In Europe, the pandemic has revealed problems within health care systems and the need to increase access to biosimilars and reform health care policies, according to a presentation at the Terrapinn Festival of Biologics Basel 2020.

of Samsung Bioepis’ proposed ranibizumab biosimilar (SB11) show that primary end points were met for best corrected visual acuity and central subfield thickness.

The Top 5 Biosimilar Articles for the Week of November 16

The Center for Biosimilars® (CfB): I'm Tony Hagen, senior editor for The Center for Biosimilars®. COVID-19 [coronavirus disease 2019], has disrupted treatment for many patients across the health care spectrum. It comes at an inopportune time for the growth of the biosimilar market, which represents enormous potential savings for patients, as well as improved access to medicine. We spoke about this issue with Jorge Garcia, assistant vice president of the System Oncology Pharmacy Service Line at Baptist Health South Florida. Garcia is also a member of the Association of Community Cancer Centers' Board of Trustees. He discussed how biosimilar access has been affected by the pandemic and what we can look forward to.

During the United European Gastroenterology Week, we heard that mortality is rising, due to the fall off in doctor visits and cancer screenings. How is patient ability to afford care playing into all of this?

Well, I think what's really important to recognize is that this year, throughout COVID-19, oncology patients have not been coming to see their oncologists or there have been less diagnoses been made. And that's been very relevant. In fact, we now try to just run campaigns to tell patients to not delay their oncology care, to come and receive their services, especially diagnostic services, that we have found ways of conducting those tests. So, I think it's hard to tell exactly how that's affecting their ability to afford care.

Perhaps this year, they are seeing less out-of-pocket costs associated with the amount of care that they receive. However, when they do come back, with potentially delays in diagnosis and in need of more complex care, there could be a delayed onset of expenses due to patients not getting health care as frequently as they probably would have, had COVID-19 not happened.

And, of course, with people losing their jobs, they have less family income. Are you hearing from your patients that this is an issue for them? Are they applying for more assistance through the doctors’ offices? How's that going?

I think that makes a lot of sense. And we definitely have that theoretical concern. We have some patients who have lost benefits through their companies. And so, that always becomes an access issue. At that point, we actively try to work with pharmaceutical companies' programs designed to help patients when their financial abilities have changed. But, as you know, that could sometimes be a lengthy process or a process where patients don't quite meet criteria. So, there is a patient-by-patient assessment that needs to be done.

And do you think broader access to biosimilars could help with any of the problems discussed so far?

I think in general, the core value proposition of biosimilars is to reduce cost and to maintain that same high quality of biologics. And I think [after 2020], given all of the added expenses and overall financial uncertainty for health systems in general, pharmacy leaders and other administrators are probably going to have more pressure than ever before to be able to be good stewards of health care costs in general. And, again, biosimilars are like a low-hanging fruit when it comes to achieving some pretty attainable cost savings within a drug class. Biologics are among the highest cost category when you compare them with all drugs. So, I do think that in the future, this may help with the uptake of biosimilar utilization.

Now, there's a low rate of adoption of biosimilars in the United States. How do you think this is affecting the real savings from these drugs at the moment?

So, in the United States, we're only 5 years into this since the introduction of the first biosimilar filgrastim [Zarxio] in 2015. Almost 5 years in, we've seen that there is a relatively low uptake of biosimilar utilization in general. And there are many contributing factors to that. But when we look at the market opportunity, where a reference product is still being utilized but biosimilar options are available, we see that overall, not looking into any product specifically but looking at the entire market, the vast majority of that market opportunity has not been tapped into. So, I think that as health care leaders, it really lends an opportunity for us to try to rethink how we bring down barriers to be able to provide biosimilars an opportunity for higher market penetration.

Biosimilar access…what's happening at the clinic level that might be preventing patients from getting access to biosimilars? Not coming in for screenings might be one thing but, in the clinic, perhaps you haven't got enough time or [ability to] concentrate, because of other priorities, on biosimilar reviews and get doctors thinking in terms of trying new medicines.

Yeah, you bring up a lot of great points there. So, in our existing oncology patient population, for those that already have a plan of care and receive infusions, we have not seen a significant drop in patient volumes. I think patients, relatively speaking, understand that although COVID-19 is a threat, not being compliant with their chemotherapy is also a threat. So, we have to keep a balance there. And, again, our infusion volumes have not been drastically impacted.

On the clinic side, for new patients is where we see a reduction in patient volumes, potentially from patients in the community that are standing by and trying to wait for things to be safer before they come seek out oncology care. And so, probably the initiation of new treatments in general, including biosimilars and other pharmacotherapy, is seeing a slow down with regards to new patients.

I also want to say that specifically for pegfilgrastim and the on-body [Onpro] injector, we are seeing that specific biosimilar sector has been more impacted because of our efforts to try to minimize the number of visits that the patients make to the cancer centers. And that on-body injector does provide the ability to avoid 1 visit. And so, I think in the pegfilgrastim space, the biosimilar options that do not have on-body [injectors], those are definitely seeing a reduction in utilization.

That's interesting. And we're heading into our first COVID winter, or maybe, hopefully, our last, but what we'll see is even more hesitancy among patients to seek treatment and even more careful measures by doctors, perhaps, to make sure that transmission does not occur in the clinic. Can you comment on how that relates to what we were just discussing about Onpro injectors?

I think what we are probably looking at is as we continue to monitor this pandemic and as we see that the risk level is lower, practices will probably begin to shift back to more of the prefilled syringe products, because, again, that's where the cost savings are. We do not have an on-body injector biosimilar that allows us to have those cost savings. So, in the market today, the only on-body injector is the reference product [Neulasta Onpro], which we know comes at a premium cost.

So, I think as soon as the number of [COVID-19] cases begins to go down—of course, this is very specific to the geographical area—practices will probably try to make a determination as to when it's back to start shifting back to the prefilled syringe so that there could be those cost savings to the practice and to the patients themselves.

Are you interested at all to see how biosimilar usage patterns may change once the data emerges on the pandemic and how that has affected drug use across the board? Or are you already seeing signs? You just described pegfilgrastim, which is a great example, but is there anything else that you're seeing in terms of usage or anticipate?

[I haven't seen] a clear trend on how the pandemic is specifically playing a role in biosimilar adoption. I would probably anticipate that overall this year we have seen a slowdown. We are not going to conferences in person. We are not having discussions as actively as I have seen before in the marketplace to transition to new biosimilars.

You mentioned something that is key before and that is that there's a number of different priorities this year. And so, on the practice side, the leaders that would lead a biosimilar implementation have a number of other things they need to worry about. And so, I think from that standpoint, we are probably seeing less efforts and energy being devoted to the implementation of biosimilars overall. Probably next year, as we get a vaccine and probably move more into our plan for how we transition our practices back to normal, I think biosimilars will be a part of that agenda. How do we transition back to normal with some cost savings along the way?

To watch part 2 of this interview, click 

Jorge Garcia, MS, assistant vice president of the System Oncology Pharmacy Service Line at Baptist Health South Florida, discussed how the pandemic has interrupted oncology care for patients and affected the utilization of pegfilgrastim biosimilars.

Jorge Garcia Talks About COVID-19’s Effect on Pegfilgrastim Biosimilars

Here are the top 5 biosimilar articles for the week of November 9, 2020.

Number 5: Investigators at the American College of Rheumatology (ACR) Convergence 2020 meeting 

 of what they say are successful, first-time tests of a multibiomarker disease activity (MBDA) score in patients with rheumatoid arthritis (RA).

Number 4: Medicines for Europe, a generic and biosimilar trade association, contends in a 

 that legal and regulatory loopholes increasingly keep competing drugs off the market

 including one on application methods for Celltrion’s adalimumab biosimilar (CT-P17) were reported at the ACR Convergence 2020 meeting.

Number 2: Alberta, Canada’s deadline for switching patients to biosimilars is months away, but the province has already seen 

 at the ACR Convergence 2020 virtual meeting included data from safety and efficacy trials for Pfizer and Celltrion versions of adalimumab.

The Top 5 Biosimilar Articles for the Week of November 9

To watch part 1 of this interview, click 

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?

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 

 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?

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?

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?

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?

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.

Nabeel Khan, MD, an associate professor of clinical medicine with the University of Pennsylvania, explains how a recent infliximab switching study builds support for use of biosimilars and early treatment with these agents. 

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

Here are the top 5 biosimilar articles for the week of November 2, 2020.

Number 5: Biosimilar orphan drugs might not be cheaper than innovator orphan products, owing to multiple factors, but 

 could change this, a presenter said at the Terrapinn Festival of Biologics Basel 2020.

Number 4:The American College of Rheumatology (ACR) has 

 in opposing a UnitedHealthcare (UHC) plan that could increase patient out-of-pocket costs.

 and other governmental entities can get more biosimilars into circulation, faster.

 could lead to new forms of pharmacodymamic measurement that improve speed and efficiency of biosimilar development and approval.

Number 1: The FDA may require comparative clinical efficacy for biosimilar approval, but on top of all the other required and available evidence, these trials 

The Top 5 Biosimilar Articles for the Week of November 2

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.

Switching patients with IBD is a difficult decision because you’re worried about the effects this might have on disease stability. Can you discuss these issues?

Sure. So, I think this is a relatively new area. So, that is one of the reasons why there is some apprehension, because it is relatively new and data oriented. The first big trial that was published was the NOR-SWITCH study, which looked at a very big cohort of patients with multiple different conditions, and the switch had to demonstrate a noninferiority of 15%, which was met.

Since then, there have been multiple different follow-ups on this [garbled]. So, there have been more biosimilars that have been introduced to test that. So, as time has passed and more data is coming out, it has become a little bit easier to switch patients on those products. Part of the aim of our study was also to show what the impact of switching was because a lot of the European data has shown that it is safe to switch.

So, we also wanted to look at that outside the trial basis—the NOR-SWITCH study was within the trial basis—so, we looked at it outside the trial basis to see what the impact was upon switching, and we found that it was quite safe to switch the patients, at least in our preliminary data. And we hope that with this there can be further utilization, within the states, of increased utilization of biosimilars, and all anti-TNF [tumor necrosis factor] drugs for that matter.

CfB: So, you've found that switching is safe, but what are the concerns among doctors and patients when they're presented with the idea of switching and the newness of biosimilars? What sorts of concerns come to their minds immediately?

So, I'm going to break it down [into multiple parts] One is the patients. The patients want to be stable on something and don't really want to switch. The inherent thing on that basis is that you're taking something away that someone is stable on. And as the old saying goes, if it isn't broken, why fix it? I mean [those that have switched] are stable. They're doing well.

Obviously, the biggest concern before switching is about the patient's stability and then, they're a little bit worried about whether a biosimilar will have the same effectiveness as the previous drug they were on. So, they are worried that the effectiveness of the drug may or may not be the same. Those are the questions they have. Then, they're also concerned about the side effect profile and whether they're going to get more side effects or whether they will get more of a drug reaction when they switch. Those are the predominantly major questions that do come up: efficacy and safety.

Physicians also have the same kinds of questions. They may not be comfortable with a patient being on [a biosimilar]. So, there's a reluctance to switch on that basis. And as long as [a patient] continues on [a reference product] and the patient is doing well, they think that there's not really much of a need to switch. And that is perfectly understandable. You have somebody who is doing well and is stable on [the reference product]. There's no harm in continuing them on that particular drug. And then, the other concern is what will happen to the immunogenicity, whether a patient will develop antibodies to the newer drug. And from that perspective, you may need to do multiple switches to see whether a patient will develop antibodies or not. So, those are the primary concerns. Again, efficacy and safety are the 2 basic issues that you will be looking at.

Also, what are the long-term consequences of it. This is a third concern that comes up because the data have all been relatively short term, so far. We don't know what happens in the long term. Anti-TNFs have been around for about 20 years and reference infliximab was introduced in 2000. In 20 years, there's been a good degree of data and there's a greater degree of, let us say, patient awareness. So, like with all new things, it does take some time, but in the end, our aim is to show what is the effect and what is the impact of the new change. We're not recommending whether one product or the other is better. We're just looking at what is the impact of the change and whether this is a viable thing to do or not.

CfB: These diseases are very upsetting to patients in terms of the symptoms that they develop, and this causes a great deal of anxiety, as well, for patients when presented with a possible treatment change or switch to a biosimilar?

It’s not a treatment change, so let's first discuss that. Generic drugs have been around for ages. The whole concept of switching from the original to the generic is not a new concept. That concept has been around for a while. The newer concept is that you're getting a biologic agent and now you're switching from originator to a generic biological agent. And because of the fact that these diseases, like you correctly mentioned, have a lot of potential to be, clinically, very debilitating and have long-term complications, patients are very concerned about that.

So, obviously patients are concerned about that and those are very valid concerns. And all educated patients have an idea of what exactly is going on, but this happens with every medical condition. Whenever you change an originator drug to a generic drug, people have questions about efficacy and safety. I think that can be extrapolated to patients with ulcerative colitis or Crohn disease, more so because they can have pretty significant clinical manifestations as well as long-term complications.

CfB: These issues are said to be a chief part of the resistance to using biosimilars. The VA has proven to be a good place to try a switching study. What is it about the structure of biosimilar use policies or formulary policies that has facilitated a study like the one you have done?

The facilitation of this in the VA was not based so much on policy but on the VA's centralized pharmacy benefit management system. So, if you want to do a study, you have these 9 million veterans who fall within the VA health care system. You have a record of all the medications that they're on and you have long-term longitudinal follow up. So, if you were to try to do a study in the private sector, it would be difficult because you are pulling information around from here and there.

Now, the other thing is that you can individually look at all the records to see what happened to the patient because there is so much research that is done in the VA. The VA's record system is so comprehensive, and it is shared nationally. Like I can look at a record of somebody who lives in California to see how he did after the switch was made.

Now, obviously you cannot do this within the private sector health care system because you can't access somebody in a capital health care system. [For example,] we cannot look at Kaiser Permanente's health care system and see what happened to those patients individually after switching. You may have some official medical records data on that, but they are not very granular, where you can go into every individual patient's chart and really see what exactly is happening to them.

So, that is why the VA is very good for doing this kind of research, because of the fact that you have all this data that is recorded. Especially with infusions, patients have to come in and get those infusions. So, you know exactly what is happening to those patients because they’re coming in every 8 weeks, or 6 weeks, or whatever regimen they're on. And then, you can see the impact of the change on that. So, you could probably see these kinds of things outside of the VA, but because of the way the electronic medical record system is set up and the commitment to develop this electronic medical record system for researchers to evaluate what is happening across the nation, it's easier to look at this within the VA.

CfB: Records are very important for your study, but so are policies that encourage doctors to use biosimilars. Could you have done a study like this on the private side or not?

So, let me clarify, it's not that they are encouraging all doctors to switch people. The VA is very open to letting the doctors do what they want to do. The availability and cost savings associated with biosimilars is pointed out to doctors. And if they feel their patient can be placed on that product, they can voluntarily do that. It's not something that we are forced to [do]—let me clarify that. There is no coercion in the VA. The VA does what is best for the patient and for the patient's care.

With every new drug that does come out, the VA will educate physicians that there is a new drug and that if they feel that this can be a safe substitute for their patients who are on another therapy, then they can switch them. If they feel it is not safe, then they don't have to do that. It is not that the VA is forcing every patient to automatically change over to this drug. It is a decision that is made literally between the physician and the patient. They decide whether they are going to go ahead and do that or not do that. And if both parties decide not to do that, there is no portion of the VA that says, "No, you have to do that."

Nabeel Khan, MD, an associate professor of clinical medicine with the University of Pennsylvania, discussed a study in which patients were switched from reference and biosimilar forms of infliximab to another biosimilar infliximab, Renflexis.

Part 1: Nabeel Khan, MD, Discusses an Infliximab Double-Switching Study 

Bhuvana Sagar, MD, the national medical executive at Cigna Health Care, discusses how Cigna has balanced using multiple biosimilars for 1 originator while also maintaining cost efficiency.

As more biosimilars enter the market, competition for market share overall helps to decrease the total cost of care; however, too many choices for a reference drug can create cost inefficiencies.

Sagar explained that in order to manage this, Cigna met with its large providers, including community oncologists and others, to gain feedback on current practice issues.

Knowing which drugs are on the market and which ones are gaining the most market share helps to lower the unit cost for prescriptions and ensures cost-efficiency for both patients and employers. Sagar said that working with providers is how Cigna makes sure that providers can accommodate their policies as easily as possible.

Bhuvana Sagar, MD, the national medical executive at Cigna Health Care, discusses the importance of maintaining cost efficiency when juggling multiple biosimilars for 1 originator in the practice setting.

Bhuvana Sagar, MD, Discusses Maintaining Cost Efficiency While Using Biosimilars

Here are the top 5 biosimilar articles for the week of October 26, 2020.

Number 5: Earnings fell overall for Biogen, although biosimilar revenues continued an 

 and were up 13% for the third quarter of 2020.

 discuss Amy Coney Barrett's Supreme Court seat and how that might affect deliberations on the Affordable Care Act and the Biologics Price Competition and Innovation Act (BPCIA)

Number 3: The strong growth of biosimilars Pfizer recently launched in the United States are part of the success story for the 

, although reference etanercept (Enbrel) sales have seen major erosion.

Number 2: Investigators from the University of Utah said they found no additional safety or clinical risks in a study of patients 

 from originator infliximab to infliximab biosimilars.

Number 1: Investigators derived a set of 

 for improving biosimilar use from 44 interviews with physicians, hospital pharmacists, nurses, patients (or their representatives), and regulators across Europe.