So it’s fundamental. I think the greatest value for sponsors is this ability to extrapolate between indications once they’ve established high similarity. We often hear this discussion, and Carlos, I’m going to ask you this question about the most sensitive population, that you are only studying the biosimilar limited confirmatory clinical studies in the most sensitive population. Can you help us understand what the most sensitive population means and how you choose which studies you do clinically for a biosimilar?

Sure. I just wanted to highlight a couple of things about extrapolation and I'll get to the question. It will lead to that. I want to emphasize a couple of things. Extrapolation has to be scientifically justified by the sponsor. It’s not automatic. And as Gillian mentioned, it is based on the totality of the data that show that a biosimilar is highly similar to a reference product and that you don’t expect any clinically meaningful differences between one and the other. Other aspects also taken into account when determining extrapolation, for example, include the mechanism of action. But the essential component here is that if the molecules are highly similar to the biosimilar reference product, then they should behave the same across all indications. That is number 1.

Number 2: I think it is absolutely understandable why clinicians would feel uncomfortable prescribing a biosimilar if there are no clinical data because, as Gillian mentioned, they are used to clinical data. That’s how they make determinations. So here it is incredibly important that providers, clinicians, prescribers understand the biosimilar concept because without understanding it and understanding how that leads to extrapolation, there will be this discomfort and resistance. 

I also agree that the FDA is in a really special position, because they granted the extrapolation of indications, to be able to educate about that. 

I think the last thing I’ll say and I’ll get to your question, I promise, is that for the biosimilar paradigm to be successful and for sponsors of biosimilars to be able to bring these products to market at a lower cost, the development costs have to be lower. And with new biologics, the majority of development costs are spent in clinical trials, and we’re talking about sometimes hundreds of millions of dollars, depending on the product and the size of the trial. By scientifically justifying extrapolation, then a manufacturer can do a study in 1 population, and this is where we’re getting towards the most sensitive population. The Sandoz approach to this is we try to identify a population where a few things happen. 

Number 1: We see the greatest effect of the particular biologic on that particular disease stage, so the biggest delta. And that allows us to see that if there are any clinical differences between the biosimilar and the reference product, they will be identified. So that’s one concept.

Secondly, we’re looking at populations that are not highly variable. So you can actually, when you measure the impact, attribute it to the biosimilar or the reference product. And we’re also looking at populations that are not necessarily using concomitant medications that could obscure some of the measurements that you’re looking at. So, for example, patients who are receiving other immunosuppressants may be difficult to evaluate immunogenicity on, or compare the immunogenicity between products, between the biosimilar and the reference product. So that is how we choose the most sensitive clinical population in order to determine biosimilarity. But it’s also important to note that is the last step in biosimilar demonstration. 

It hinges on having demonstrated that, analytically, the reference product and the biosimilar are highly similar, that it’s a structural and functional perspective, that you’ve demonstrated, if applicable, in preclinical models that there’s no difference from a clinical performance perspective, and that you’ve evaluated bioequivalence to pharmacokinetic, pharmacodynamic evaluation in patients or in human volunteers, depending on the situation. So this is the last step in the biosimilar development paradigm, if you may, and hence, why the ability to extrapolate from that indication hinges on all of the other information and data. 

I think you’re making a good point there. These are confirmatory studies.

And if you haven’t established high similarity analytically in the first place, you can do all of the clinical studies in the world and you’re never going to be a biosimilar. So I think it’s very important that the clinical studies address what is variously called “residual uncertainty.”

Videos

Selecting the Most Sensitive Population for Confirmatory Trials

 So, I’m going to move to the next issue, which is extrapolation, which is another much misunderstood issue. So by way of introduction, extrapolation is the use of a product for more than 1 indication, but for a biosimilar, when the studies are limited to other than complete clinical studies in every indication. Now, it’s the same as comparability, where if you make the same molecule, ultimately, it has to do the same thing clinically in all of the indications.

So I think what’s confused this debate a lot is that people are assuming it’s extrapolation between indications that may be fundamentally different diseases. So I just want to clarify that it’s not. It’s the same molecule, and it has to do the same thing as the reference did, as the premanufacturing change did. But it does mean we have more limited clinical data sets specific to the biosimilar on the day the biosimilar is launched.

Physicians are used to seeing clinical studies on each indication at the day of approval and launch of an originator product. So maybe to our physician, how much is this misunderstanding, based on the molecular match being the basis of extrapolation—how much is that confounding biosimilar uptake if there are no specific clinical studies on the biosimilar available to put in front of the physician?

 So, I want to answer that question in a couple of different ways. First of all, extrapolation is something that’s very important—that the FDA kind of grants its designation to a drug when it’s approved, and maybe the FDA can play an important role in helping physicians understand what extrapolation is. And the second thing is, in oncology, if you trace back the history of how we use drugs, a lot of times we may not have phase 3 randomized controlled studies in all of the indications that we use. We initially, before [the National Comprehensive Cancer Network, NCCN] came into existence, used to use compendia listing for indications that were not part of the FDA-approved indication.

Subsequently, with NCCN establishing a robust pipeline evaluating, analyzing, and granting these data—like, you know 1A, 1B, or 2A&mdash;we are very comfortable that even if the drug has not undergone all clinical trials in all indications, if it comes into the guidelines, whether they’re the [American Society of Clinical Oncology, ASCO], [American Society of Hematology, ASH], or NCCN up to 2A, we would be very comfortable using that drug in those categories. Now, what the FDA could do is to help physicians understand about how extrapolation is kind of derived, and how it probably would be helpful.

Also, getting into the NCCN, or ASCO, or other guidelines would help a product get appropriate payer coverage, because we just don’t need to kind of look at the approval process; we also want to look at are payers and whether we cover that or not.

So, I think extrapolation is a very important part of the educational piece that does to be highlighted, and the FDA would be the most competent authority to do that in conjunction with not-for-profit educational forums.

The Extrapolation of Indications

 For clinicians, do you think this whole idea that the originators vary but biosimilars vary too, and they’re all within the same range as overseen by the same people at the FDA—is that a useful message?

 It probably would be a very useful message because there are a lot of physicians who are on the fence right now, not understanding the class as a whole. So something coming out from the FDA highlighting that the originator has undergone multiple modifications without compromising the quality, efficacy, or safety—it would reassure the physicians who are prescribing that yes, I’m not going to compromise the quality of care because I’m choosing something that’s likely less expensive but I’m going to sustain and maintain the quality of care.

It would be extremely helpful information coming out from the FDA. Because for me, I don’t have personal expertise in judging all these aspects. But I trust the FDA as a very reliable source of information that would help me make very important treatment decisions.

 And this is a good message, I think, that the FDA is doing its job. They are overseeing all biologics to the same standard, consistently. Therefore, physicians, patients, providers can have equal confidence.

 Just to give an idea of the scope of biologics that have been available since recombinant technology actually became available—we’re talking about the 1980s&mdash;there’s a recent publication&mdash;actually, this year&mdash;that identified approximately 260 biologics that have been approved since. And you can expect that virtually all of them, or most of them except maybe the most recent ones, have undergone some manufacturing change. And in just 3 cases were there any issues between the pre— and post–manufacturing change product&mdash;1 of them having some significant safety issues… and some of these happened, like, decades ago, right?

 And the scrutiny and the process and the released specification for products now are even tighter, but that should speak to how controlled manufacturing changes are and how the comparability exercise is so very well refined. And understanding, again—like you mentioned, Gillian&mdash;that the scientific concept behind comparability and biosimilarity is the same would, I think, go a long way in accepting biosimilars as high-quality products.

 And certainly one thing that I’ve always noted is, given the extent of the data by about the time a biosimilar is approved, on both the originator and the biosimilar, we do have to bear in mind that the product that we always know the least about at the point of initial approval is the truly innovative product, and we all want those approved. This is a risk—benefit exercise. We’re trusting the FDA to it, and they’re doing it based on some very, very well-founded science and principles. So I think that context is important because we want the new, cool products too.

Clinicians' Understanding of Manufacturing Changes

 So, comparability is an issue that’s raised in the context of biosimilars. Comparability is a regulatory tool developed in 1996 whereby manufacturing changes can be made to an existing biologic. Then it was adopted internationally in 2005 and under so-called [ International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use, ICH]. Now, comparability—you can make a manufacturing change to an existing biologic as long as you show that the critical product quality attributes, including immunogenicity, haven’t changed. That’s been used extensively for many products including, I believe, infliximab&mdash;it’s published; it’s been used over 50 times since the product was approved.

Now, I say in general and shorthand, that makes every originator biologic essentially a biosimilar to itself. It’s been subject to changes, but the important point is, the clinical outcomes are no different. In the US, it’s an entirely confidential trade secret when comparabilities occurred, and most physicians, most providers, and patients—they don’t know that’s happened to their existing medicine because the label on the product doesn’t change.

 And because there’s no difference in the clinical performance.

 You could say that comparability is already the standard for extrapolation between indications and even interchangeability. So from a manufacturing perspective, does it matter? Is it important for physicians to know about these changes in the US in order for them to be more comfortable about biosimilarity? How much do you think education goes back to these fundamentals, understanding the variations of biologics both batch to batch, pre— and post–manufacturing change? But fundamentally, to this citizen petition that the clinical outcomes are unchanged—that’s the important other part of both comparability and both biosimilarity.

So, Carlos, do you find, as a manufacturer, there’s any understanding? Is there interest? Where are we on this fundamental understanding of biosimilarity and comparability being the same as a scientific asset?

 So, manufacturing changes, as you mentioned, occur frequently, and they’re there for very good reasons—for example, if there’s a scale-up in the manufacturing process that represents a change or there’s a change from one manufacturing line or facility to another or if there’s an improvement in the process. All of these are good justifications for manufacturing changes. But they do introduce potential variability in the product from an analytical perspective, from a characterization perspective. And again, as you mentioned, the pre—manufacturing change product and the post–manufacturing change product have to be shown to have the same clinical efficacy, safety, and no difference, no change in immunogenicity.

This is not well known. This is not well known among providers. In fact, when you describe this manufacturing change and the fact that it does result potentially in a change to the product, they’re not aware. But I think what’s critical is also what you mentioned. These changes occur frequently. They occur for good reasons, but there must be a demonstration that there’s no clinical impact. And they can happen multiple times, as they do, and you mentioned the example of infliximab. It’s been available now for a long time and has undergone many manufacturing changes, some of which are relatively minor; others may be somewhat less minor.

But as long the pre— and post–change product is shown to not have any change in the clinical effect, then the product remains on the market. There’s no change in the label. And I believe in that case, it’s interesting to make that known, because it provides some insight into biosimilarity because you’re absolutely right—the scientific concept between the comparability exercise of manufacturing changes and the biosimilarity exercise in demonstrating that a biosimilar is highly similar to the reference product is essentially the same. And you get a lot of “ah-has” from prescribers, even more so when you mention, then, that it is conceivable that a reference product is a, quote, unquote, “biosimilar of itself” over time&mdash;that also raises an ah-hah moment. And I believe that for products that have been on the market for many, many years, a product that was first launched compared to a product that’s currently available in the market is probably a different product from an analytical perspective, but, again, the efficacy&mdash;the clinical performance&mdash;has to be the same.

 So basically, what we know, then—and FDA did lead the world in 1996 with comparability protocols as the basis of manufacturing changes&mdash;is that the FDA knows how to do this. That’s 22 years of experience, by definition, with the very biologics that are the referenced products for biosimilars.

So, Julie, we talked about the experience in Europe. The European regulators have been absolutely explicit that biosimilarity and comparability are the same. Do you think we need that from the FDA too? Is that an opportunity—again, in terms of a primary source of educational materials&mdash;for FDA to add to this clarity? That doesn’t mean they have expose for individual products when comparability is being used, because in the US, that’s a trade secret; in Europe, it’s public. But would it help for the FDA to articulate some of these primary principles and, quite frankly, laud their experience on successful use of comparability?

 Thanks, Gillian. And yes, I think it would be supportive and helpful if the FDA was to clarify this. But I think—and I go back to what Carlos said&mdash;it’s important to understand that both Pfizer and Novartis Sandoz are innovator companies and biosimilar companies, as well. And I think if the FDA could clarify this but also clarify that the standards for biosimilar and its innovator biologic or its reference product are not different…So, I think those are very important as far as manufacturing changes, comparability, the data, and everything else goes. So we need to simplify that message. The FDA should take the lead on that and then continue to provide…

 This is not anything new we’re asking really at the FDA.

 In fact, they’ve got everything on their website, which I personally find phenomenal, because there’s so much stuff there.

 But you need to know for it look for it, so we’re essentially asking simple summaries.

What Juliana is asking is the basics, right? Just understanding some of the basics would clarify some of these misconceptions. For example, the quality standards and requirements of biosimilar manufacturers and reference part of manufacturers are exactly the same. As Juliana mentioned, at Novartis, for example, we manufacture our original, originator biologics and biosimilars in the same manufacturing facility. So the standards are the same, and this is the same in the [European Medicines Agency, EMA] as it is in the FDA. There’s this perception that somehow the standard and the requirements for biosimilars are lower than the referenced products, and that’s just not true.

Biosimilarity, Manufacturing Changes, and Comparability

 Let me address the comment that Kashyap made, which is that the FDA approves a product, and then your opinion is that the responsibility for education should be more at the provider level, or from providers or personal societies.

Again, as I mentioned, I think every stakeholder should be involved in education, and it can take many forms. But what we’ve observed from the FDA in the last year or 2 is a different approach.

For example, when they published their biosimilars action plan in July of this year, that is something that I thought was somewhat unexpected from the way the FDA normally operates. I think it has a lot to do with their perspective—a lot to do with the Commissioner, Scott Gottlieb, who really believes that biosimilars are part of the solution to increasing health care costs, so they’re taking action. We’ll see how far it goes, but I have expectations that they will actually adopt a different approach to biosimilar education and their interest in adoption in a healthy biosimilar market rather than the FDA did before.

 And then others can get that information out there.

The FDA's Approach to Biosimilar Education

 So, what I’m hearing a lot of is basically that the business model is not relevant to the safety, efficacy, and quality of these products. The FDA has made that determination; they then need to help get the message out. So, do you believe that the primary source being FDA is essential to the physicians, the stakeholders you work with? How does the dissemination by others make a difference, or doesn’t it? If the FDA is the primary source, is that the only source? Can we accept European analyses? Are they pertinent, or does it all have to come through the FDA?

 So, probably there’s a difference in the European healthcare market and the US healthcare space. In Europe, you have the government-controlled contracting system. If the government decides they need for a common entire country, it’s going to be utilization, and then they’ll go with that.

In the US, you have to realize that the FDA’s role kind of pretty much is done when the information is sent out, but then you have to jump through the hoops of physicians, you have…[GPOs, group purchasing organizations], you have a contracting structure. Here, like, 50 states—and each state has its own managed Medicaid plans. You have Medicare Advantage plans, and you have pharmacy benefit managers. So the system is a lot more complex in the US compared to Europe.

So my suggestion is, yes, we definitely need the reassurance about the safety, efficacy, immunogenicity, and other relevant parameters of the biosimilar class as a drug class. But for the utility pattern, for the end users, unless physicians who are the gatekeepers of prescribing medicines—unless the message is out to them, either through national meetings, associations, not-for-profit educational utilization forums like this one&mdash;it’s not going to have an uptake. So no matter how many things we do to FDA following the [EMA European Medicines Agency] model, in the US, at the end of the day, the part of panel, the prescription of physicians, is the one that will determine the utilization?

 Yes, that’s where it’s worth emphasizing…and then, Juliana over to you…that most of these medicines are both prescribed but also administered by the physician. And in that sense, they’re a little bit different from a lot of the drugs where they’re dispensed in pharmacies separately from the person who prescribes them. So I just want to make that point clear that the physician is intimately involved in both prescribing and administering the medicines. Juliana, you had a point there?

 No, I agree. But I do think…the physician plays a very, very key role in all of this. So does the insurer.

 The insurers need to provide access to these products. The insurers and the [PBMs, pharmacy benefit managers] need to cover these products. But the FDA needs to combat the misinformation.

 What we’re thinking, then, is a catch-22.

 Because the biosimilar cannot say it’s better, then. Therefore, most physicians, most providers, could say, “Well, if we stick with the reference, that’s fine; we’re getting that option available to our patients.” So, we’ve got to level the playing field so that the value in terms of competitive pricing, alternative supply of the biosimilar, can contribute, get market share, and be part of this multisource marketplace that we now see in Europe.

 Yeah, a competitive marketplace. And you’re proactively engaged across stakeholders to support biosimilar uptake. It’s not going to just happen if not all the stakeholders are engaged. I’ll talk a little bit about what Carlos mentioned about what we did with EMA when we first launched, and the EMA had their congresses and continue to have them. Because we don’t have that model in the US, the Biosimilars Forum, of which we’re members, started that model independently, and the FDA—every few months we have over 60 stakeholder groups to a workshop and the FDA is there, the EMA is there. We have multiple physician groups, pharmacy groups, patient groups. Payers are there. It’s about supporting the biosimilars market. What do we need to do? And we started just with education and how we can get that. And as you mentioned, everyone has different information, and that’s why it’s very key that we go back to the one trusted source of information and education about biosimilars, the FDA. We also have to simplify this. We’ve made it very complicated. And really the source, the FDA&mdash;there are no clinically meaningful differences in a biosimilar, and the safety and efficacy is there. It’s that simple. We need to simplify it.

 And that’s what we’ve seen in Europe. So maybe the most pertinent information from Europe is in their multiple, multiple million days of patient treatment with these products, that is in 10 years what they’ve seen.

 Seven hundred million patient days of experience over 10 years and no difference from a clinical perspective. No unexpected adverse events that you otherwise would not see with a reference product. That’s a lot of experience.

 And the EMA published that. The EMA—so the authorities, the regulatory authority published that information and those statistics in their educational materials for healthcare providers.

US Versus EU Education on Biosimilars

 Well, then certainly I think what we’ve seen is that half of the problem is not exclusively wrong in the statements, but they’re ill impressions, and it starts with the name. For basically 15 years, we’ve seen that “biosimilar” means similar and not the same. But that forgets about no meaningful clinical differences having been determined by FDA. Now, obviously at this point in the debate, we’re not going to rename biosimilars as anything else. So what do we now do about it, given that complete information is a challenge? People use shorthand. Does this mean that we have to target specific populations in those settings where this misleading information is already out there? Is it certain stakeholders? For instance, you’ve alluded to the patients perhaps being less concerned if their healthcare providers have confidence.

So, is it physicians, patients, nurses, payers? For any of the panel, are there particular people who’ve got to have this full understanding, using FDA with primary sources? FDA does have on their website already that every biosimilar approved by them is as safe and effective as any other biologic. What is the form of the information that we need? What do these stakeholders need to receive?

 So, I think the stakeholders need to receive, and this is key in order to combat the misinformation, they need to receive the FDA educational materials. And as either industry or physician groups or patient groups, other stakeholders—insurers and payers&mdash;we need to help disseminate that. We need to proactively help the FDA to get that&mdash;those materials&mdash;down to the physician office level. It’s the source. The FDA needs to be the source of all truths about biosimilars.

 Just as in Europe we see all that with the [EMA, European Medicines Agency] and with the commission. Carlos, as a physician and as a sponsor, what have you seen similarly? You have launched products, too.

 Sure. A couple of thoughts based on the question that you asked: You’re right that because biosimilars are highly similar to the referenced product but not identical by the nature of the fact that they’re biologics. That is a handicap, if you may, although biologics are inherently variable. That’s just the way they are, because unlike a generic that is manufactured through chemical synthesis, biologics need to be produced in living organisms, and that by its nature introduces some variability that occurs from lot to lot, for example.

And I think a lot of the misinformation or misunderstanding comes from that. A generic is identical to the reference product because it’s a small molecule, and, therefore, you expect the same clinical effect. Biologics are so complex, and the biosimilar is not identical to the reference product; maybe you’re going to see some difference in clinical effect. But like you mentioned, even though there is this variability in biologics that makes a biosimilar not be identical to the reference product, it must meet the criteria of no difference in efficacy, safety, and immunogenicity, and I think that’s what’s lost. And I think education—basic education&mdash;on what a biologic is would go a long way, obviously adapted to the audience.

But to add to what Juliana said, where should the source of education come from? Certainly the FDA, I completely agree. It’s a trusted source; it’s independent from manufacturers. But I’d like to talk about how EMA went about this, right? EMA started education, but they brought in a series of stakeholders in order to create guidance documents. This included manufacturers; it included professional societies; it included patient and patient advocacy groups; it included payers and others. And so now they created this consensus among all stakeholders that put out educational material, and I think went a long way. I think the FDA should look at that and maybe try to do something that is similar.

In the end, I think it is a responsibility of many stakeholders to educate about biosimilars—not just the FDA&mdash;and it could be done through a single multistakeholder setting, but certainly patient advocacy groups, professional societies, manufacturers, and managed care to their membership should also assume that responsibility. I think for biosimilars to succeed…the educational effort has to be multiprong.

Targeted Education for Biosimilar Stakeholders

 So, one would be most polite in using the term “misinformation.” What are we actually saying? We’re saying that some companies are promoting a concept that is overtly misleading, that biosimilars are somehow—let’s say, less effective&mdash;in nature of their development, which means they’re less reliable than the reference product, is that right?

 So…those misleading pieces of information are outlined in [Pfizer’s] citizen’s petition. But I want to go back to what Carlos said—and we saw this when we launched the first biosimilars in Europe 10 years ago, and the same misinformation was introduced in Europe, and we’re seeing that again today in the US, and it’s to lower the confidence and the prescribers and the patients in using biosimilars.

Ten years ago, we asked the [EMA, European Medicines Agency] to help us with that, and the same programs and actions…that Carlos outlined were taken by the EMA 10 years ago, where they were the source. And this is key. The FDA, like the EMA, needs to be a primary source of education on biosimilars regarding their safety and efficacy, and we need to help distribute and disseminate that information.

The FDA, like the EMA, needs to combat the misinformation that’s out there about biosimilars and send letters to these companies, the reference product companies that are doing this, or other organizations. It’s time. We need that here in the US.

 So, Kashyap, as a physician, as a provider, what have you seen from the clinical side, working with patients about this sort of misinformation that’s out there? Are you seeing it in day-to-day practice? Do you understand what’s being alluded to here by the sponsors?

 Thanks, Gillian. I think I have a little different perspective on this. I was not so much aware of this misinformation campaign, for the lack of better words. I wouldn’t use that, but I’ve done some intensive physician education at 5 national meetings in the last 2 months, and I was very unpleasantly surprised to find out so many misconceptions among physicians who are the prescribers.

I spoke at 3 large meetings and 1 of the national conferences, and the first question a lot of physicians asked me was “So, what’s the difference between a generic and biosimilar?” And I said, “Oh, where do I start here?” Because there’s a huge difference between a generic drug and a biosimilar. The generic drugs do not have the new trials; they are simply chemical components called [API, active pharmaceutical ingredient]. You buy it in a bulk, like kilograms or a ton, and convert them into the tablets.

But because there was a perception that there’s not a lot of difference between the generic drug and biosimilars, they say, “Well, why are they priced so high?”

And I said, “Listen, these drugs have to undergo multiple steps that establish the totality of evidence compared to the referenced product. It’s not an easy task. It’s not an easy solution, and that’s 1 of the reasons why you don’t see a huge price, or you definitely would see some of incremental decline in the price, but you don’t expect them to behave like generic drugs that happened back in 2004, 2005, 2006, when the paclitaxel went generic, when carboplatin went generic, when cisplatin went generic.”

So there’s a lot of misconception. It may not be intentional that they’re not learned, but we have to do a lot of—at least now&mdash;education at the physician level to have them become aware of what biosimilars are as a different class.

And the second observation I made was that patients were not as much reluctant with biosimilars, and then I’ll share, when our discussion points in the direction, that for patients who are least likely to resist adoption of biosimilars, I think the providers, the nurses, the mid-levels, and maybe the peers of the team that we need to work with in educating about biosimilars and what the class of drug is.

Combating Misinformation and Misconceptions About Biosimilars

 Hello, and thank you for joining The Center for Biosimilars

 Stakeholders Summit entitled “Provider Education on Biosimilars.” I’m Gillian Woollett, senior vice president at Avalere. Participating today on our distinguished panel are Juliana Reed, vice president, Corporate Affairs, Global Biosimilars lead at Pfizer; Carlos Sattler, MD, head of Clinical Development and Medical Affairs at Sandoz; and Kashyap Patel, MD, medical oncologist and CEO of Carolina Blood and Cancer Care. Thank you so much for joining us. Let’s begin.

So, Pfizer recently submitted to the FDA a citizen petition asking for guidance on how product sponsors can communicate about biosimilars. Why did you see the need for this citizen petition?

 Thanks, Gillian. So, Pfizer saw in the marketplace educational materials and other materials created by reference product sponsors that created doubt and confusion about the safety of biosimilars. These materials, as we create the doubt and lower the confidence, will lower the uptake of biosimilars, so we felt it was necessary to file the citizen petition and ask the FDA to proactively do something about the misinformation about biosimilars in the marketplace.

 So, Carlos, does Sandoz have an opinion on both the issues raised in the citizen petition and also the ask that Pfizer has for FDA to provide additional guidance?

 Thanks, Gillian. We do, we actually do. We’ve also seen a lot of misinformation out there on biosimilars. I think it’s really important to take into account the following: Healthcare providers, prescribers, must be free from any influence that inhibits them from making the best decisions for their patients. Misinformation and unbalanced information on biosimilars inhibit them from making these decisions. So we believe that something must be done, and we agree with the citizen petition. But beyond the citizen petition and the fact that it requests that guidance be authored or created by the FDA in order to take care of this misinformation, there are other steps that the FDA, we believe, can take.

For example, they could partner with a Federal Trade Commissioner and identify the sources of misinformation. They could send letters to the sources of misinformation, to the companies and others that are doing this, to tell them to stop. They could make the names of these companies and other groups that are spreading this information public so that stakeholders, patients, physicians and others know who are spreading this misinformation. And finally, they can continue with the educational efforts that they’ve embarked on but specifically addressing some of the topics of misinformation that are out there.

Pfizer's Citizen Petition on Biosimilar Communications

Do anticancer biosimilars have a role in bringing down the cost of oncology care?

The role of biosimilars and the cost of cancer care remains to be determined. There is little doubt that the introduction of generics in the small molecules made a tremendous difference in terms of reducing the cost of cancer care. It was counterbalanced by the introduction of predominantly new biologics.

So that was the last 10 years, and now we’re entering a phase where the equivalent of “generic” biologics is starting to make an impact on the market. What we saw in the small-molecule generic was discounts ultimately as high as 80% or 90% as the third or fourth generic drug came to market. It has been argued that we will never see that kind of a discount in the biosimilar market because the compounds are far too complicated to manufacture and the regulatory burden on manufacturers to meet FDA muster is substantially greater, and that’s undoubtedly true.

But let’s remember that if you look at the cost of care over the last 10 years—the rise in the cost of cancer care related to drugs&mdash;are actually due to 2 classes of agents, 1 being oral specialty pharmacy agents where the increase is by far the greatest, but the second are the biologics.

So, even a 10% or 15% discount for a biosimilar agent that is embraced by the clinical community could mean millions or even billions of dollars for a payer. So, the answer is yes.

Now the fascinating thing is this week*, Coherus announced they were going to come in at 33% lower than the reference product, which is Neulasta. That has rocked the market a little bit and may wind up being a bellwether for what we’re going to see as we see other biosimilars, including the big therapeutic biosimilars which we’re going to see coming in the next couple of years—biosimilars for Herceptin and Rituxan&mdash;we will see.

 reduce the cost of care. The question is how much.

Michael Kolodziej, MD, vice president and chief innovation officer at ADVI Health, Inc, discusses how much anticancer biosimilars will impact the cost of cancer treatment.
 