Amgen Inc. (AMGN) Earnings Call Transcript & Summary

[Audio Gap] what's happening out there. So I'm not going to introduce everybody and waste a lot of time because we've got 5 panelists. But I'll just give you their names and titles. We've got Eva Temkin, who's acting Director of Policy, and the Office of Therapeutic Biosimilars and Biologics at the FDA. And Julie Jamil, who is Biosimilars and Policy Science person for Medicines for Europe. We've got Martin Schiestl, who is the Chief Science Officer at Sandoz, part of Novartis. And Leah Christl, Executive Director, Global Regulatory R&D Policy at Amgen. Before that, 14 years, I believe, we saw you at the FDA. And Stacie Ropka, who is a partner at Axinn. So thank you, panelists for joining us today, and I'm going to jump right in because we have a lot to talk about.

So let me start with Europe. We'll start with Martin and then go to Julie. And why don't you tell the audience what you expect from the clinical biosimilar development world to happen from the regulatory perspective in the future. Tell us what you're expecting in Europe. Martin? Tell us who you are first and then tell us what you have to tell.

I have to just start with the first just the correction of the top titles and interactive regulatory sales policy at Sandoz.

First mistake of the day.

But I'm with the development organization of Sandoz since 25 years. So since the beginning, when we started into biosimilar endeavor. And especially the question you raised on the clinical development piece and the biosimilar development is one of the hot questions at the moment. It was always discussed throughout the year, and we have seen also developments like excepting biomarkers instead of this very large efficacy studies. But in the last 2 years, the discussion has increased on the value of this efficacy studies as a whole, and there are quite some papers and also discussions at conferences, all of this and the predecessors. And also last year, they came up guidance from the U.K. regulatory agency on streamline development. And I think this is also the way the future will look like so that we also see more complex biologicals, which can be developed as biosimilars without the need for this very large efficacy studies. So that evidence to insure safety and effectiveness of biosimilars will be done by other means on the quality part, on the kinetic sides, additional data studies, but I think this is a major development we're seeing right now. Certainly, it will take time, but I'm pretty sure that in the long run, we will see adaptation of these requirements.

And so are you saying there'll be less data needed for require -- needed for approval, more data or just different data?

I would say different data. I mean, we have seen in the last couple of years, what we can do, for example, at the quality level. Questions can be discussed there in south already there. There is now plenty of experiences in clinical trials, comparing biosimilar candidates and reference products. So therefore, I would say it's a slight shift in the data. But in a sense, to use them more efficiently and to even come to better decisions when it comes to biosimilar evaluations.

So Julie, you're with Medicines for Europe, why don't you tell us what you do and what your take is on this?

Thanks, Andrew. So yes, at Medicines for Europe, we are a trade organization, representing the interest of patent medicines producers, and that includes biosimilar makers. I think just to bounce on what Martin has just said, and zoom out a little bit. The regulatory framework actually serves a purpose for patients for accessing -- making medicines accessible. And I think the pressure we've seen on health care systems over the years and more, obviously, recently, I think is showing that this efficiency gains need to be achieved throughout the framework and regulatory systems, obviously offer some room. And in Europe, now we have 15 years of experience. The first biosimilar was approved in 2006. There's been many applications. I think there's been 70 approval or nearly 70 approvals. That means there's a lot that has been processed, both in terms of approval, but also those applications that have not been approved. And all that is a massive amount of data that can inform better the regulatory process. And again, at the service of an efficient regulatory framework. So I think that's basically -- I'm expecting like Martin that this will become a reality, the shape of which is yet to be formed again as we discuss the best way forward.

Okay. Well, thank you for that. So let's skim across that ever-warming pond over to the U.S. And Leah, why don't you tell us what you're thinking from a U.S. Perspective, what the future is holding?

Sure. So I think the U.S. perspective aligns very well with the global perspective, really. And when we're talking about this evolution of the data that we might be seeing, I think it is important to remember regulators like the EMA and the FDA, I think, have always taken a flexible approach in terms of what data would be necessary to support biosimilarity. I think that's been a hallmark of especially both of those 2 regulators. And that has influenced the global regulatory environment. There's certainly no one size fits all. There's been -- what's been referred to as the totality of the evidence approach. So I think there are evolutions that we're seeing in terms of scientific methodologies, what it is that we know about biological products, how they work, why they work. But there really isn't, again, a one size fits all. And I think we're going to see FDA and EMA be more open and hopefully, that will influence other regulators about what types of data and studies are really necessary to demonstrate biosimilarity, looking at those evolutions in science and making sure that we're answering the questions that need to be answered about biosimilarity. But there still are products that we don't know a lot about. And there's new biologics being approved all the time. So you're always going to be in that place where you know more and more about products the longer they're on the market. But if you have newer products that are on the market and you have those intellectual property protections are expiring and they're on the market for a shorter period of time where you might expect to have biosimilars coming on to the market, you still might need some different data for those newer products than you might for some older products where you would have some additional knowledge on. But I think the regulatory pathways are set up to allow that and then to recognize that from a scientific perspective and be flexible. And I think that's the good thing about the regulatory pathways that we have, and we've had over the years.

Yes. So before starting with Amgen, you were at the FDA for more than a decade. And based on those years, do you agree with Martin that we are going to see even in the U.S., different types of evidence? And is that evidence going to be really based on the product moving forward? Or is it going to be as you say, blanket regulatory policy for all biosimilars?

So not to age myself here, but it was 16.5 years.

16.5.

So as I said, I think that the regulatory pathway in the U.S. from day 1 has been flexible in a way to allow this approach of different types of data. FDA has already approved products based on pharmacokinetic and pharmacodynamic endpoints versus more traditional efficacy endpoints. And so that's what we're talking about, where you have the knowledge of the products, and you've been able to move forward, again, about understanding how they work and why they work in the body, you can target the data that you need to look at, are there clinically meaningful differences between the products and look across the spectrum of different scientific studies, whether they be in the analytical space, looking at functional data or pharmacodynamic endpoints versus those traditional clinical endpoints. And so I think that's always been there. So I expect that FDA is going to keep moving forward with that same type of an approach. And Eva can comment on this as well from the FDA perspective. But I think in my experience, my time at the FDA, it was one of the reasons that FDA was hesitant to put out product-specific data or product-specific guidance because it does remove some of the flexibility on that product basis about what data you might need depending on what you're seeing with that particular product. There certainly are products where we know enough like insulin, where you can have product-specific guidance that would make sense, but it doesn't make sense for every product and you want to preserve that regulatory and scientific flexibility for what it is we're talking about.

And Eva, that was a great introduction.

Yes. Thanks. And since we're doing bio correction time at the beginning, I also have to -- this last Friday was actually my last day at FDA. So I'm back in private practice as of this morning. But happy to talk a little bit about these issues from my very, very recent experience at FDA. And I think that there's taking kind of a step back, there's a real push and pull that regulators are grappling with around these issues. And on the one hand, there's a desire, and I think appropriately a desire to have efficiency wherever we can and to really harness the flexibility that's built into the section 351(k) pathway, and to exercise that flexibility appropriately. The other side of that coin is that we also have patients and health care providers that need to be driving uptake and utilization of these products. And in order for that piece of this puzzle to be successful, we need to think about what are their expectations. What are they use to seeing biosimilarity and interchangeability are really complicated context for a lot of patients and for a lot of health care providers that are used to seeing large amounts of clinical data and labeling? And so biosimilars are sort of uniquely situated in that they both have this flexibility, but also an expectation of a certain amount of data associated with them. And so as we have mentioned, as we have different levels of comfort and experience with different products, we're able to exercise that flexibility more and more. And so I would like to point to the guidance that we published, the draft guidance that FDA actually [indiscernible] something we published on immunogenicity considerations for insulin products, specifically in November of 2019, which was a really big effort that my office undertook to put out into the world flexible thinking on products that we really understand well, that they're well-characterized or relatively simple structurally. So we were able to say in this context, in these circumstances, we know that we don't need this particular kind of data, right? So there's an opening of a real example of that kind of flexible thinking. I know that FDA and OTBB, in particular, is working really, really hard on additional product class specific guidance. There's actually a mechanism built into the statute for publication of product class specific titles. And I think that being able to get that thinking out into the world as it develops and solidifies, will be really helpful in this space also.

Well, it's a really good perspective. So there's a number of lawyers on this panel, but the one we're going to go to for the legal analysis is Stacie. So Stacie, why don't you tell us what your perspective is of what the future for biosimilars and biologics on the regulatory side holds?

Well, let me just say for a moment that I was a scientist for over 20 years before I became a lawyer. And so if I can just put my science hat on for a second, I would like to add to what Eva just said about insulin. I was getting a graduate degree in the early to mid-80s in endocrinology, and we were discussing insulin then. And I just want to say that now that the insulin products are being regulated as a biologic and as Eva said that FDA put out a guidance for how interchangeability in the United States might be found for insulin products. I'm really sincerely hoping that insulin, so well-known and a fairly simple protein that FDA will be able to work with those who are thinking that interchangeable designation so that the immunogenicity clinical trial, which seem to drive up the cost of development for follow-on biologics will not be required. And that FDA can then leverage this outcome for other molecules, again, perfectly appreciating that starting with other simpler proteins to build confidence in that process as a whole. But insulin, as many people probably know, it made the move just about a year ago from being regulated as a drug to being regulated a biologic. And by putting it into the biologic regulatory category, it means that any of the follow-on products are going to go through the BPCIA pathway and will be subject then to FDA's regulation. And this gives FDA an opportunity to approve a product under a pathway that they've been able to work with very successfully for many years, but now they're going to be able to marry a simpler protein with a path that they understand and perhaps come to some conclusions about what people do seem to talk about. I know we're going to talk about more later on these trials about immunogenicity and how that can be shortened or improved so that it doesn't become the financial burden that it can be for biosimilar or interchangeable development.

And I just want to jump in and add one thing on the insulin guidance, which is exactly what you're saying, safety, that what that guidance really says is that for biosimilar and interchangeable insulin products, the agency is not expecting to require comparative clinical immunogenicity data. And I'm a lawyer and not a scientist, but my understanding is that the elimination of that requirement will save many, many months and potentially millions and millions of dollars from the development of similar and interchangeable insulin. And so hopefully, can catalyze some additional development of those products?

Yes, absolutely.

And so since you brought up a specific disease diabetes, I'm going to bring up another one, which -- or at least a category of them. It's not a secret that the next round of medicines going off-patent that will open the door for biosimilars are in the orphan drug space. And they -- those types of drugs present their own unique challenges, right? So why don't we go to the regulators first to Leah, tell us what are some of the unique challenges that orphan drugs, biosimilars may face? And what is your expectation of what's going to happen soon.

Right. So this space for orphan and rare diseases has been the topic of conversation for many, many years. And I think it remains a topic of conversation regarding the challenges around this because it's not overtly easy, developing any product to treat an orphan or rare disease is challenging in and of itself from the standpoint of conducting clinical trials where you have a limited patient population, and again, really understanding how to create a data package that's going to be support of that program. When you're talking about biosimilarity, it can be considered even more challenging. You have issues for a biosimilar manufacturer about access to the reference product, which a lot of times for orphan and rare conditions is heavily controlled. And so you're trying to have access to that product so that you can test it and then develop your own manufacturing process to create a biosimilar that's highly similar to that product. So that's kind of part of that first challenge. Then when you're thinking about what additional data do you need, and then we look towards the concept of comparative clinical testing, whether that's pharmacokinetics, pharmacodynamics, traditional efficacy endpoint, comparative immunogenicity, all product-specific factors that you would look at. Those same types of challenges come forward if you have for testing even an originator product in that setting. Again, small populations that we're talking about and the concept of being on clinical investigational treatment when there's maybe something out there that folks are stable and comfortable on raises some additional challenge. And so I think here is the place where we talked about before, to have these scientific and regulatory flexibilities. We need to have a balance, as Eva talked about with having a pathway and data expectations that health care providers and patients are understanding that regulators really are having a sound approach to that you are answering the questions about biosimilarity that need to be answered. And maybe this patient population is even more concerned about that of making sure that, that product is truly biosimilar and there's truly no clinically meaningful differences. But where should you look for flexibility from the regulatory and scientific side. Can you conduct studies maybe in healthy subjects because you're looking for certain endpoints? Certain -- if you're looking for pharmacokinetics, so exposure in the body, does that need to be in a patient population or can you have some flexibility there to answer this question about similarity of exposure in the body to make sure that the product is going to be circulating in the same way, getting towards the target in the body. So those are the kind of flexibilities that we can look at. Are there things that Martin alluded to for the analytical side of things from the structural and functional standpoint, how well do we understand that molecule or other things that we can do outside of clinical studies that would give more data around similarities between the products to be having the answers to those questions about biosimilarity. But again, recognizing for health care providers and patients that they need to have confidence in what regulators are doing. So you can't just throw out the standards and say this is hard. So we're going to sort of lessen the data package simply because it's more difficult. We need to find ways that are right from a scientific perspective to answer the questions, to maintain the confidence in this regulatory pathways and what regulators are doing when they're approving a biosimilar.

So you bring up a really good point. And Eva, I'm going to ask you in a second to dovetail off of what Leah said. But can you address the following proposition. The proposition is that if you want biosimilar uptake, you've got to have buy-in from the physician and the patient community, unless you're going to live in a country where they make them both irrelevant and the payer just makes all the decisions. But assuming that we're not in those environments yet, whatever. What is your take on how changing the data maybe arguably lowering the data, some may argue that you're lowering the data, how would you address that when you're just starting to get buy-in from the physician community, especially -- and Julie, I'm going to come to you with this in Europe because you've had buy-in with the physician community. And that buy-in, I think, over time, has resulted in greater uptake and confidence in biosimilars and greater patient understanding of them and many places around the world model -- want to model what the European experience has been. So there's a lot there. So Eva, why don't you tell us what you think about that because we're nervous, the patient community, which is, I think that -- wait a minute, we're just starting to accept these biosimilars, now you're going to change the data required for it. We know that means you're going to lower it, and we know that they're going to be unsafe, right?

Not right. I do think it's a delicate balance. I will say, if I've learned anything in my time working on biosimilars, it's how many stakeholders really need to come together to make this program successful. So it's the regulators, the industry, the patient groups, the health care providers, the CMS and reimbursement and insurers, the patent folks, we work with the FTC. There's -- across the board, there's really multi-stakeholder effort that's necessary, but I do think 1 thing that always comes up is the importance of patient education and health care provider education and comfort levels in those groups being really key to success for biosimilars in the U.S. And I think information and comfort level really varies across different disease categories and different types of health care providers. So you may see very different acceptance from the oncology community, from sort of the GI community, from the diabetes community, it's a really wide variety. I think one thing that I feel very strongly about and that I think is really important to keep in mind is that there's not a lowering of data. There's not a lowering of approval standards. So that's not something the FDA does, right? We have an approval standard. And any products that we approve or that the FDA-approves and we keep touching myself, any product that the FDA-approves is -- has met that standard, right? And there may be different paths to get to that same endpoint. It may be that 1 product is approved based on more analytical data or tighter analytical data and a different PD endpoint or whatever it is that gets us there, but I don't think, ultimately, we need to quibble about whether or not the standard has been met because we can have faith in the FDA approval process on that front and know that approved biosimilars are safe and effective, just like their reference product. And before return, I might just to touch on the orphan's question. I think a lot of these issues are really scientific issues, and they're the same scientific issues that plague orphan product development in all product categories. They're not necessarily unique to biosimilars, right? So enrolling clinical trials is difficult when you have small patient populations. And all of those difficulties that we think of when we think about orphan development. And I think, ultimately, for biosimilars, the key is going to be really thinking about extrapolation and the way that we've done that for indications and cross indications for biosimilars, and whether we can harness any of that thinking even in other product categories to really help support work in development. So I just wanted to touch on that too.

That's a good point. So Julie, you and Europe have been long lauded as being the pioneers of biosimilar development and have really shined in how uptake can be accomplished, including all stakeholders, in my opinion, anyway. So what about the orphan drug situation in these rare diseases where you're not going to have the largest patient populations to pull from. What's the European take on that?

Yes. Thanks. So I think I would like to reconcile what the considerations we've had on the science and the regulatory with the other side of the coin, and you refer to patient views and what's the take there. I think in the orphan space, in Europe, at the moment, at least, we're up for a very big overhaul of the regulation and legislation around this. Because still there is an assessment of the 10 years of the legislation in Europe and a feeling that, yes, it has delivered. So there are more medicines available. But the price tags are really high. So it's both a problem for patients and for health care systems, if there is no perspective of competition ever. And I think that's another part that we need to reconcile. Also within the existing medicines that have orphan indication, there is still inequity in access, depending on which country across Europe you're looking at. So when you have both this overall access and the very long-term impact on health care systems and the equity issue. Obviously, a natural way of thinking about it is how can we foster competition there when time is right. And I think that's why I'm expecting that there will be quite a substantial amount of discussion, again, not only scientific, but bringing the science and the regulatory processes to serve that purpose and meet those objectives -- of health objectives overall. Also for Europe, what we've looked at is, it's about 30 products that are going to lose protection exclusivities or less. So that's a nonnegligible pool of products for which competition could be there. But one of the really key point is for the orphan originator product development, so every innovation about it, there's been a lot of support by the regulatory processes, a lot of incentives all along the development to foster that development and to help create those new medicines for patients. I think one reflection that we may have, again, collectively with the patient groups, with the doctors, with the payers is, is it possible without incentives or without even looking at the suitability of the existing framework for off-patent competition to get that competition going. And what we see, again, facts for now is that less than 11% of those orphan biologics have candidates in development at the moment, biosimilar candidates. So that gives you a little bit of a perspective on the difficulty probably for developers to overcome the risks that are set for in front of us at the moment.

That's a really good perspective. So with that, I'm going to move to the next topic, which is something that's been talked about as long as I can remember, real-world evidence, really hard to say. But real-world evidence has been something the patient community, the physician community is longed for, for a long time. And all of a sudden, another silver lining of COVID, it seems like every day there's another real-world evidence story coming out about COVID of this population and that population and the vaccine works on this one, and these are side effects. And the amount of data that's coming out in almost real-time is really hard to keep up with, at least, and mind boggling, but amazing from our perspective compared to when we used to see data. We're in 2021, so the latest data we had in 2017, and so we're going to build policy off of that. So real world data now is something that's completely different from how we used to talk about it. So why don't we jump in, again, with the regulators first here. Eva, why don't you tell us how real-world evidence is going to play a role in the future of biosimilars?

Sure. So I think it's a tough question. I do think there's generally a role to be played for real-world evidence and real-world data in product development. What that looks like specifically for biosimilars is a little bit tricky. And I say that partly because if you think about what we've been talking up about for the last half hour, which is streamlining clinical programs to support the demonstration of biosimilarity and really the commensurate focus on the analytical data, it's not clear how that fits in with the idea that we should be turning to or relying on real-world data to support a demonstration of biosimilarity. And so I'm curious, I don't know if Leah, you have thoughts on kind of where this is all going from the development perspective. But I do think there needs to be more discourse around it and more conversation about what -- one, what is the role? Two, what does the data need to look like in order for it to be useful and reliable? And how can the FDA then incorporate that into review of 351(k) BLA biosimilar, the same way that there's, I think, legitimate questions about what those things look like for an innovator biologic.

Yes. And so Leah, what do you think on that?

Yes. So if you said, Andrew, I think this concept of real-world evidence and real-world data is expanding over time. And I think it's encompassing data that maybe wasn't really the first thing that people thought about years ago when we started talking about real-world evidence that it was a very clinical focus and it was supposed to be, maybe answering questions in lieu of clinical trials. I think we have an opportunity here in the face of biosimilarity to use the real-world evidence and data that we're seeing to help support development, especially around biosimilars. I think it provides opportunities for learning about the biological products that are on the market. What we would be concerned about from a safety perspective, if you have rare adverse events that you might not see in a clinical trial, but the product has been on the market for a certain amount of time, that can help to inform the development of a biosimilar about how you should be designing any sort of studies? What endpoints or what data would you want to be collecting? Where would your concerns really be that you would want to focus from a similarity standpoint about ensuring that the products were truly similar? So I think that there's a lot of opportunities to use this evidence and data maybe differently than folks originally thought it might be used, specifically in this space. But to Eva's point, in order to do that, it does have to be collected in a way where you can tease that information out, but then also there's sufficient data and information to be informing decisions, informing trial design, informing how it is that you might be using endpoints that can help give information about even pharmacodynamic endpoints, how does the patients are responding, making connections between what would be more traditional clinical efficacy versus things that you might look at that we refer to on a mechanistic pathway. So biologically, how is it working? Are there other things that you could look at? So I think that there's a way to mine the data ultimately, but it does have to be collected. It needs to be there. It needs to be sufficient. And it needs to be collected in a sound way so that you can have confidence and then using that data in the ways that we're talking about.

Julie, what about the European perspective on this?

Thanks. So I think just bouncing back. I think one of the safeguards that we really need to have in the framework is that obviously, everybody loves data. And a lot of us have sometimes scientific background, and so more data the better. I think the safeguard that I would call for here is -- and the question is, for what purpose? Because we can collect a lot of data and turn out that, like a few years down the road, we're asking questions to a database that's very rich, but that does not answer your actual question. So I think it's very important we ask that proactively because there's a lot of means today to process a large, huge amount of data. The only underlying thing I would say is let's have a purpose, an agreed purpose, be it regulatory or other. And in Europe, we've had a few experiences where, for instance, medical societies have used registries, for instance, in the biosimilar context to look at, can I use this medicine earlier, not that the treatment cost is more efficient. So for instance, in chronic diseases, let's use that in rheumatoid arthritis a bit earlier. And that is really useful. It's useful for patients, it's useful for doctors, it's useful for health care systems. The thing is, we were lucky if -- in a way, because the question was asked, and it could be answered. But I'll come back to that safeguard because I think it's really important we know why we're collecting data, what's the intent and the intention behind.

One idea that I think you're -- I completely agree with you, Julie. I think it's a really good question. And the 1 idea that kind of always comes to my mind in the answer to that question is, at least in the U.S. context, when we're looking at products that are approved as biosimilar and that may be thinking about making a move to interchangeability, is there a role there, particularly with regard to immunogenicity, when we have experience using a product as biosimilar, how can we harness that experience to make the move to interchangeability. And I think that's like a really good idea of like the -- an example of the kind of purpose that you're talking about?

I would like to add that real-world evidence helped a lot to increase confidence in biosimilar, many of you mentioned of interchangeability. I think they have a lot of switching evidence now there. And what Julie mentioned also that with evidence of the originator product, of reference products can also inform biosimilar development. And Julie, you mentioned also that -- so the monitoring of the product on the market, there are always scientific questions, very real-world evidence that a place. It will just go to 1 potential area of application that was just discussed by the real-world evidence can inform approval of biosimilars. And here, my personal opinion is that real-world evidence is maybe a good tool for innovative product development, but not so much for biosimilar because it's not sensitive enough to detect the differences of products which are already similar. So therefore, it's my personal, yes, opinion here that all this evidence needs to be created pre-approval, does not mean that it needs to come from clinical pieces, but it can be on structural analysis, functional analysis and other means. But I'd argue to separate really the -- what is the question we have on the table and what is the best tool to solve it. And I think then we can get much more clarity of the use of real-world evidence in biosimilar development.

All right, can anyone else make comments they want to share? All right. So one of the things I'd like to do is work in questions from the audience during the presentations if they fit because often, we don't get to them at the end. And so Martin, while you have the microphone, one of the panelists had -- one of the panelist -- one of the...

I would say, the increase of the scientific knowledge of these products, and for those who are not familiar with this guidance, I mean it's really revolutionary in a way that it proposes it for many, if not most, future bias of candidates, no clinical comparative efficacy study is needed. And this goes beyond what is currently already accepted for molecules like filgrastim or insulins. There is still some efficacy comparison, at least at an earlier endpoint or in this case of pharmacodynamic endpoint is necessary. So this is really the revolutionary new concept. But it's -- I think it's based on reviews of biosimilar approvals up to now, also evaluating the value of these studies, what's the sensitivity of these studies and also acknowledging the state-of-the-art we have now at the analytical and functional characterization. So I think it's really the way it will go. Certainly, it will take time until those products will hit the market, so to say. And maybe this also addresses one aspect, which has been discussed here at the panel earlier, and this is about the confidence in this product. And that -- especially as prescribers, the patients need to have this confidence. But when we look at the U.K. guidance, it will take, I don't know, 3, 4, 5 years until this product will be there, and I hope that at that time, people will much better understand the biosimilar concept per se, what is the database behind it and therefore, has also a chance to be accepted by the users and patients?

So Leah, I know I might be catching you off guard because I don't know if you've read the guidance, but you were very involved in creating the guidance for the United States. What do you think about the new U.K. guidance, if you know anything?

Yes. Yes. Quite familiar with it. So I think as we spoke before about sort of the evolution of regulatory standards. As Martin said, I think that what MHRA has done in terms of issuing this guidance has taken that very big step forward for the things that we've all been talking about, about the evolution of the data that's necessary to support a demonstration of biosimilarity. I think all of us recognize that there's a way maybe to view products on a continuum. We also have to recognize that globally there's not a definition of biological products. So there's differences in -- especially between the U.S. and Europe about what they consider to be a biological product. So we have some products that are regulated with biosimilars in Europe that are regulated as small molecules under a different pathway in the U.S. So I think the regulators have, again, taken different approaches about what data is necessary to support approval of those products through an abbreviated licensure pathway. And as we spoke before about, I think that regulators have always tried to maintain flexibility there and really think about what data is necessary for that specific product for approval of the pathway that they're under. Again, I view things on a continuum that there are certainly products where you know a lot about them. They're well characterized. You can have a very robust analytical characterization, how they work, why they work, you know the things about them in terms of their critical quality attributes, you may have good pharmacodynamic endpoints, good understanding about them. But then there's going to be products that are more complex, that maybe you have some uncertainty about the mechanism of action. Maybe you have multiple mechanisms [indiscernible] uncertainty about biosimilarity coming out of that analytical exercise where then you would look at what additional clinical data is necessary. I think that the MHRA guidance still include those concepts of looking at things on a product-specific basis. I do think that this is a very bold step to say, in general, they didn't think that compared to clinical data would be needed. As Martin alluded to, that might take sort of time to implement as to what that really looks like in practice. So I think the evolution and more and more of a view of biosimilarity of looking at a product-specific level and thinking about products on this continuum of complexity and what we know about them.

Anybody else have anything to add? No. Okay. So another good question came from the audience. And it said that what are the panelist thoughts about Europe and the U.S.A. having mutual recognition for product approval? In other words, if the FDA approves it, EMA automatically approves it and vice versa. This has been talked about for a number of years.

I can give it a go. I don't think that's a very common discussion point we have among industry participants to this biosimilar field. But I certainly, looking back to the question we touched upon on orphan, I think that is making a bit of more sense because if you see regulators are working on joint assessment on some very complicated, very difficult or narrow population or difficult to make products. So in a sense, I'm not talking about mutual regulators being actually able to do that. But yes, that's my take on this personal piece.

Yes. It would be certainly nice from, I guess, the cost perspective and from getting access quicker perspective if they had cross approvals. I know a number of countries will look at a drug and say, well, if this is approved by the FDA or the EMA, then we're going to automatically approve it. I wonder if the WHO has a role there or you think that each country wants to have autonomy and have their own regulatory systems set up and approval set up, anybody?

Go ahead.

Eva, go ahead.

I was just going to say, I think it's an interesting idea and maybe one that is more complex than it might seem at the initial level. I actually did a lot of work on the first mutual reliance initiative in a different role at FDA, and the levels of complexity in getting to that point I think, can't really be understated. We have different legal systems. We have different health care systems. We have different disclosure permissions and requirements and protections on intellectual property. And so navigating that, I think is complicated and difficult. And the one thing I would say that I think kind of dovetails with the question, maybe isn't exactly the question, is how do we support global trials, not necessarily in cross approvals or reliance on approvals for approvals, but how do we support the kind of need that industry has to have data generation and trial that can support multiple regulatory regimes across the world.

And Martin, what were you going to say?

Yes. I'd say it's a mutual agreement of biosimilar approval will be a kind of utopia, so but from my experience in the industry, I would say, we were quite happy if the detailed requirements, like for example, on the study endpoints, are converging so that it's easier to make program which can be approved by both regions. And to your comment, Andrew, what the other countries, so there are quite a lot of countries were accepting an approval by FDA or by EMA to make a more formal approval in their country so that they don't repeat all the review stuff. So there is -- and also at the WHO level, there is also a lot of encouragement to work sharings between agencies. So not everybody has the capacities like EMA or FDA has. So this is a very important aspect here.

Yes. From the layman's perspective, it seems like it could be done. It seems like put the legal stuff aside, put the different health systems aside, if you could just agree on what should it take for approvals of these drugs, and there could be some mutually agreed upon body that says we have prove it and everybody agrees. I know it's a fantasy, but it sure would be nice. Although from the patient perspective, I think I like the safeguard that independent bodies around the world are evaluating these drugs independently, it's another safeguard, but it's at quite a cost to the health systems and ultimately to patients and providers. So -- I interrupted somebody.

Yes, I was going to say with this, I think this is something that FDA, EMA and other regulators have tried to look at. And so FDA and EMA way back when started to biosimilar cluster to try to talk about study design aspects to help look at scientific alignment, recognizing that the concept of harmonization, where everyone agreed on the certain regulatory aspects of it or has a mutual recognition or reliance aspect is, is challenging. Again, there's the differences in the legal pathways in the health system. But I think as regulators, FDA and EMA originally looked at one point the FDA had their legislation and said, hey, we should talk about where we can have scientific alignment and really focused on that. And over time, that grew to include Japan's regulatory agency, Canada. I think it's expanded since then to include some other regulators as Swissmedic, I think. I don't know if anyone else has joined, but really looking at trying to focus on the scientific aspect to help support global development. As Martin indicated, there is a lot of support from WHO in terms of helping to give advice about what pathway should look like in these emerging markets that where maybe they don't have the same regulatory capacity to then provide them with support. There's also the International Pharmaceutical Regulators Programme that was looking at how to help support again these emerging market areas by looking at training opportunities or white papers, looking at the regulatory consensus about how to approach things like extrapolation and issuing white papers to help support what regulators are doing. So for those who want to do their own review, that they had a good framework to do so and help to sort of globally align the concept of even what a biosimilar was, that it was compared to a reference product and the types of data that would be expected.

Anyone else on this?

Yes. Andrew, so I think what's very important, and I think I echo what Leah has been saying, I think, again, if we shift a bit perspective, U.K. recently separated from EMA in terms of regulatory jurisdiction. And so while an evolution of any kind is really welcome, and that's, I think, how science should make things move. I think another angle is really to look at that we are not creating divergence at least for too long or -- because that is complexity added to how you develop medicines. And I think cluster like ideas, like Leah was referring to, are really needed to keep that conversation going and keep maybe the dialogue and alignment going forward because complexity is never really, really linked to access or availability in the end. That is just an additional hurdle.

Yes, really good point. So we only have a couple of minutes left. So I think I'll just ask one general question to the panel. We're living still in the time of COVID and the pandemic. We've seen clinical trials slow way down. We've seen approvals be affected by not being able to go in person anymore. These hearings and how all these in-person reviews we've seen slowdowns all across the drug cycle, except for COVID. So how will COVID affect biosimilar development, say, this year, 2021 or 2022? Or has anybody heard anything about how it can have long-term impact? Anybody have any thoughts on that?

So I'm happy to start with that just from a development perspective. I think for the development of biosimilars, we've seen the same impact, as you said, on ongoing clinical trials or initiating new clinical trials, thinking about how to change how we're approaching clinical trials. And it's not an issue that's specific to biosimilars. And I think that regulators have looked at where they can have flexibility, incorporating aspects of telemedicine, different types of oversight, different types of way to collect data remotely. We've seen a lot of digitalization that's coming into this as well to keep these development programs moving forward. I think that there was that slowdown, that little blip of everything is coming to a halt and things having to change, but I think regulators very quickly stepped up and worked together globally how to keep drug development moving. So I think that those flexibilities, once they were implemented across the board and obviously this did impact biosimilars as well. But then we saw development be able to continue in a more seamless fashion that we were used to, but just with the differences that were implemented. I think now going forward, there's a discussion of what flexibility can be retained, whether that, again, more remote clinical trial management, digitalization. And again, this is not a biosimilar specific issue, this is any drug development program that we're talking about. What types of alternative tools can you put into place for facility inspection, whether it be for a new product or you're doing post-market surveillance inspection and thinking about, again, what regulatory flexibility can remain in place. They are still sound and fit for purpose and make sure that the appropriate safeguards are still there. So I think going forward, that's going to be a big topic of conversation for regulators.

Really good point. Anyone else?

Developers are still interested in developing biosimilars. And if there was any slowdown experienced in 2020 because people were staying home, not in the lab as much, there is still -- there's still a desire to develop biosimilars. They still reach out to me to ask about how -- what biosimilars they should pursue from a patent standpoint because [indiscernible] helped them out with the due diligence. So I suspect that the pipeline, if anybody else has noticed that if it's been slightly, I don't think it's going to disappear. I think the pipeline is going to start flowing again so that as things shake out better at the research and development level, we're going to see the pipeline filling up that way, and it will go forward. And then in the regulatory realm, you'll be fed again, an FDA applications will come in and approval process as we go forward.

And I think to your point, Stacie, too, as we come out of the pandemic hopefully, we're really going to, I think, see an increased or renewed emphasis on patient access and drug pricing and how do we create cost savings for the health care system overall. And any time we talk about that, I think biosimilars are a really big piece of the puzzle.

I would even go further. I think the necessity imposed on that by the COVID pandemic has created a lot of innovative way to look at the use of biosimilars. Changing the practice, using them early in prophylaxis, et cetera, just because that prevented people from getting infections by going to the hospital, for instance, or things like this. So there's been a very fresh eye at looking at biosimilars, not as just replacing something, but as just something to do more with what exists already. And I think that's also a dynamic impetus that we're seeing.

Really good points, everyone. So we have come to the end. Thank you, Martin. Thank you, Julie. Thank you, Stacie. Thank you, Eva. Thank you, Leah. Thank you all for your time. Thank you to the World Biosimilar Congress for inviting me to moderate this panel. And stay tuned for the next panel. So with that, I will end this. Thank you all.

Thank you.

Take care everyone. Have a great day.

Thanks, again.

Thank you.