 titled “Regulation, Policy, and Litigation in Biosimilars.” I am Amanda Forys, senior director of Reimbursement Policy Insights at Xcenda. Participating on our distinguished panel are: Ha Kung Wong, partner at Fitzpatrick, Cella, Harper, and Scinto; Molly Burich, associate director of Public Policy: Biosimilars, Pipeline, Reimbursement at Boehringer Ingelheim; and Dr Angus Worthing, practicing rheumatologist at Arthritis and Rheumatism Associates, and chair of the American College of Rheumatology’s Government Affairs Committee. Thank you so much for joining us. Let’s begin.

First, we’re going to talk about biosimilar regulation in the United States and Europe. The FDA is currently reviewing industry feedback on its interchangeability draft guidance. Molly, will biosimilar manufacturers seeking interchangeability have an effect on how reference product sponsors attempt to protect market share?

 That’s a great question. I think it will. I think the purpose of interchangeability, from an FDA standpoint, is really geared towards proving that switching products for any given patient will result in the same clinical outcome as the originator. Therefore, we believe that the designation of interchangeability will be meaningful. It will be meaningful from a patient standpoint. Hopefully, it builds their confidence in the product they’re taking. We really believe it will be meaningful from a physician standpoint, as the data will be built and designed exactly for switching. So, we think it will have an impact on behavior across the industry for those designations when they’re given.

 Yes, I’d like to also mention something about reference product sponsors (RPS). I think that to a certain extent, they’re really going to move to protect their products even more strongly because of the fact that interchangeables act like traditional small molecule generics. They can kind of piggyback on the marketing and education of the branded drug. And so, they’re going to look for ways to protect and get additional IP (intellectual property). And, I can see a lot more challenges from interchangeable manufacturers on IP that is owned by RPS. In particular, of the interchangeable guidance, they actually talk about how product presentation, for instance, including labeling, packaging, and delivery device design is actually really important and has to be looked at. And because of that, I can see reference product sponsors looking to get IP around those aspects (to kind of protect their market share as well).

 Yes, and that’s a great point. I think that the interchangeability guidance was probably the most long awaited guidance that the FDA released, as it pertains to biosimilars. There were industry, physicians—every stakeholder was really interested to see what the FDA was going to require. I think the reality is, it’s a high bar and appropriately so for what it’s trying to prove.

Biosimilar Interchangeability and Market Share

 Dr. Worthing, we don’t have an interchangeable biosimilar on the market yet, but how would the designation of interchangeability affect you as a provider in your clinical prescribing practices?

 Great question. Molly is right—doctors and patients have been waiting, I think, for the interchangeability guidance. I think it would help build confidence. As a rheumatologist and somebody who writes prescriptions for biologics, there’s 2 general situations in which a doctor might write a prescription for a biologic. One instance is for a patient whom hasn’t taken the drug yet, and they’re new to the drug. And then, there’s the situation where we’re writing a prescription for somebody who’s already been on the reference product for some time, might have been doing well, and we’re writing a prescription for them (for the biosimilar) to change over and move. I think in the first instance, we’re getting a really good amount of confidence in the FDA pathway, which shows that the structure, and function, and anticipated usefulness, safety, and efficacy of biosimilars are biosimilar to their reference products. And to me, that kind of matches up with the first clinical situation&mdash;where I’m prescribing a biosimilar to a patient who’s not yet taking a drug.

Where the interchangeability pathway comes in boosting confidence is in that second situation—where a patient might be doing well on a drug and both the doctor and the patient are interested in knowing if a biosimilar (which might be cheaper or they might have easier access to it), is going to work the same way, not cause any more side effects, and still keep their disease under control. And that’s where I think the pathway that the FDA has drafted, which we saw this winter, really helps boost confidence. The pathway suggests a clinical trial design where manufacturers start patients on the biologic reference product and then switch 3 times (to the biosimilar, back to the reference product, and then back to the biosimilar), and confirm that they’re just as safe and effective. I think that will help (in that situation). We can be confident in telling a patient, “This drug might seem new to you, but it’s going to work just as well as the drug you’ve been taking.”

 That actually ties a little bit into a follow up question I was thinking of. You’re currently comfortable with the pathway. You’re currently comfortable with a patient (as you’re saying, kind of a new patient) and a new start with the FDA guidance. This is really about that switch patient (your continuing patient), and thinking about switching therapy. What evidence are you currently relying on (looking at products that have been approved) to make sure that you’re comfortable prescribing them?

 Right now, we’re looking at 2 different kinds of evidence, mainly. One is looking at analytical data. That’s data in the test tube, and data about the molecule and how it works, and looking at the mechanism of action to make sure it works the same way as the reference product. And then, the second kind of data is clinical trial data. Clinical trial data includes putting the drug into people who have the disease (where the drug is applying for indication) and making sure that it works just as well and has as few safety signals compared to the reference product. So, right now, we’re looking at those 2 kinds of data and judging that these biosimilars work just as well as their reference products.

 Can I ask a question, Angus? I’m kind of curious about this. As a first-designated interchangeable gets approved into the market, do you think this is going to be a tipping point, where because biosimilar uptake has been a little bit slower than anticipated, more physicians will be more likely to prescribe biosimilars? Or, do you think that they’re going to start saying, “Well, biosimilars are somewhat inferior to interchangeables,” and just ignore them because they don’t have switching studies? They don’t have the presentation studies and the FDA’s blessing.

 Great question, Ha Kung. I think that depends on a lot of variables. One is looking at how good the data is for that interchangeable. We want to see the data from clinical trials right in the FDA package insert. We want to know about them. All doctors, when they’re talking to their patients, should learn about the drug and how well it works. I think if that happens, and then on the payer side, people who are paying for the drugs (insurance companies, pharmacy benefits managers, the government), if they also see the value of the interchangeable drug, I think that we’ll get good market uptake. You were referencing how the biosimilars market hasn’t taken on as quickly as hoped. I think we’re all interested (from a provider’s and patient’s perspective), in getting the prices down. That’s all we’re talking about today with biosimilars—trying to reduce the prices. And really, that’s probably going to hinge on market uptake and getting more biosimilars into the market.

 Yes, and I would totally agree, Dr. Worthing. Coming from a manufacturer’s perspective, I think it’s very important that all stakeholders understand that a biosimilar that’s “just a biosimilar” is not less safe or less quality. It’s quite the opposite, actually. I think the bar for biosimilarity is high, to Dr. Worthing’s point around analytics, in particular. But, I think it’s going to be beholden for all stakeholders to understand that, in fact, a product with just a biosimilarity designation isn’t less anything. It’s different. If you pursue interchangeability, the purpose of that is different. Therefore, I think to Dr. Worthing’s point, manufacturers will look at things, product by product, and make that decision, which is a very significant investment. As Dr. Worthing mentioned, it’s a large-scale clinical trial. Because of the number of switches, it requires a lot of time. Therefore, it’s not an overnight proposition.

I think we’ll see some molecules in some markets where interchangeability is very important, and I think we’ll see other areas where it’s less important (because of how the product is given to the patient or in the disease area). If it’s for an acute use in oncology, I think you’ll see that things will look very different (from an interchangeability standpoint) versus in a chronic use, where a patient might be on it for years or decades.

Interchangeability and Rheumatology Prescribing Practices

 When we’re talking about the confidence in the biosimilar pathway and achieving biosimilarity, a lot of my colleagues and experts (in the biosimilars field) will discuss a biosimilar as being akin to a new batch or a new lot of a reference biologic drug. And the way we talk about that is we know that since 1998, when the first biologic in rheumatology was approved, that drug is different from the drug that’s coming under the same brand name now. It has shifted because of a change in manufacturing techniques (often improvements). We now know, with analytical detail and technology that’s available these days, that a biosimilar might be more like a current reference biologic than that reference biologic was similar to when it was started (when it was first FDA approved). And thinking of it in that light, you can consider a drug that has achieved biosimilarity status, according to FDA, as a new batch or a new lot of the reference product.

 I was just thinking that since you’re a specialist, that might be something that you would look one step further at (to figure that out). But for the average healthcare provider, they may be looking at this from the perspective of the history with small molecules, where you have a generic drug which has an exact ingredient that’s identical. They say that a pharmacy, or a pharmacist can actually make that substitution and that the interchangeable is really kind of the biologic version of that. Whereas, the biosimilar is just another product. So, in some ways, if you’re looking at it as somebody who’s not digging deeper, doesn’t it somehow make it sound like the interchangeable has been blessed by the FDA as being safer or substitutable for this product?

 Yes, I think that that’s certainly part of what some people are thinking. I think the FDA has made it very clear that that is not true—that it’s less safe because, of course, the hurdle for biosimilarity is where you determine whether the product has enough of the analytical similarity to be considered similar. But I definitely agree. There will be that perception, and I think that, in part, that’s why Europe doesn’t have the designation of interchangeability. And the reason for that is because they believe in the science of biosimilarity. They leave it up to the individual countries to decide. Hindsight is 20/20, right? We’re only 7 years in (in the United States), but I think that thinking that there could be a perception that an interchangeable is a higher quality product or has a higher level of safety or efficacy is incorrect. I think the FDA will continue to try and reiterate that. The reason why they’re 2 different designations is they’re approving 2 different things. It’s a worthwhile point because I think stakeholders, as they learn more about it, couldn’t actually go to that. And the truth is, it’s a different pathway and it’s a different approach from small molecules for many reasons, and the least of which is the complexity of the molecules.

Molly brings up Europe and I think that’s an astute observation. The difference between the biosimilar pathway and the interchangeable pathway is probably in the eye of the beholder, at this point. For me, biosimilar designation means that a drug is expected to work as well and have the same safety issues as the reference product. Like I said—a new batch of the old reference product. On the other hand, I think interchangeability is an excellent idea in the multi-payer, multi-state market (like in the United States as compared to Europe), because patients that I prescribe drugs for can be expected to move, change insurances, graduate into Medicare or their formulary, or their same old insurance might change year to year. They may actually expect to switch back and forth from a reference product to a biosimilar, so I’m thrilled that the FDA proposes to study drugs like that.

Biosimilars, Interchangeability, and Perceptions of Safety

 Let’s talk a little bit more about the FDA. A recent paper argued that bridging studies are redundant and should not be required in the clinical development of biosimilars. What potential challenges could be associated with using a single global reference product?

 As Dr Worthing mentioned, it’s a great question. Reference products, in a lot of ways, are biosimilar to themselves. Your product that was created in 1998 looks very different than what’s being manufactured in 2017. I think that the FDA, including bridging studies between the United States, the European Union product, and the biosimilar is really just trying to ensure that any differences (that would be natural because of the process of these) are accounted for, clinically, and are reflected in the clinical data of the product. It’s certainly possible that the agency’s thinking evolves as the biosimilar pathway evolves.

For now, I think the bridging study that’s required makes a lot of sense to, again, build that confidence in physicians who will write prescriptions for biosimilars, payers who will potentially require them, and patients who ultimately take them and want to make sure they’re getting a high-quality product that’s not going to create any issues with their disease.

Yes, I have to agree with that. I’ll just say that biological products, with different manufacturing sites and, of course, post-approval changes in manufacturing (and this is something that Angus and Molly mentioned as well), there is some product drift. There can be some issues there. You don’t want to have differences that emerge in the critical quality attributes of the product. So, I agree. It definitely makes sense the way it is.

Global Reference Products in Biosimilar Development

 The FDA and EMA [European Medicines Agency] have signaled a need for greater regulatory alignment in terms of sharing inspection information, and the agencies have entered a new agreement to share full inspection reports with one another. How has the industry received news of this change in the types of information being shared among regulatory bodies?

 My impression, from at least people that I work with, from the intellectual property (IP) side is that there is some concern about the fact that confidential information can be included in these types of reports. And they are, often, because a lot of this is manufacturing information. In the United States, obviously trade secrets are very important to manufacturing. A lot of those things can be included in these inspection reports. Typically, the FDA has been sharing redacted reports to take out the trade secrets. But with this type of cooperation, which is good, you want to have cooperation and want to make sure resource management is done correctly. But you always run the risk of disclosing those trade secrets.

As anybody who’s worked with trade secrets knows, once it’s out there, it’s out there. You’re not getting it back. KFC’s secret recipe of 11 herbs and spices—when it’s out there, it’s gone, right? You’re not going to be able to recover that. The more times it’s duplicated, the more times it’s sent out. You send it out to a regulatory agency in Europe and they say, in their press release, “This agreement recognizes that Europe has the authority and demonstrated ability to protect confidential information.” Well, that leaves industry in the position of crossing their fingers and hoping that’s true. It’s a little bit scary, from an IP perspective.

 Do you think that this type of relationship is a wise use of resources? Or, do you think this is something that could potentially delay approval and subsequent availability of biosimilars?

 I think it’s to be determined, in a lot of ways, because it’s a relatively new development. But, I do think that the timelines, often, are different between approval in different countries. So, that’s built in to the process already. I think the bigger question is, how much are the agencies going to be able to keep what should be proprietary, proprietary?

 Yes. Since 2012, the FDA has had authority to actually share the trade secret information to European regulators, but they haven’t. They’ve actually only given redacted reports. So, it goes to show that the FDA does understand the importance of this—to, particularly, biologics. A lot of times, that’s the really important aspect of making your product.

Inspection Reports and Proprietary Information

 Now we’re going to talk about reform at the agency state and federal levels, which is definitely an interesting topic in today’s political climate. Let’s talk about the FDA first. In the FDA’s drug price action plan, the agency explains that it will prioritize the review of generic drug applications until there are 3 approved generics for a given small-molecule drug. Is there any expectation that the FDA would do this for biosimilar products?

 I don’t know if there will be, but I think it’s a possibility. My only concern is that I don’t think that it actually gets them to the market any faster. In the typical situation, you’re looking at this new biologic exclusivity that exists, and that’s a 12-year period where you can’t get approval of a biosimilar anyway. In getting priority review, the FDA can be slow, but 12 years slow is pretty slow. I don’t know if that’s going to be an issue. Now, that does make a difference, obviously, to some of the things that are being looked at today. Like Zarxio and 

, that regulatory exclusivity is already gone. In that respect, perhaps that might help, but I don’t really see the real benefit. With the small molecules, that was kind of a policy that was put in place in light of this high profile Daraprim and EpiPen (epinephrine) stuff that was going on in 2016. Their goal was to try to increase competitors for products that have already gone generic. That’s not really an analogous situation to a biologic BLA [biologics license application] product and biosimilars.

 That’s an interesting perspective. Molly, do manufacturers see this issue differently?

 I agree with much of what Ha Kung said. I also think part of it is that we’re 30-plus years into the generic pathway. At this point, the FDA, in particular, Commissioner Scott Gottlieb—who has probably been one of the more vocal FDA commissioners on lowering drug prices, given what a challenge they are in the United States for patients to handle&mdash;is broadly trying to implement policies on a pathway that’s been around for a while. We’ve certainly seen success in lowering drug cost and high levels of generic utilization across the country. I think that it’s probably too soon to implement something like that for the biosimilar pathway.

I agree with Ha Kung that I’m not sure it really speeds anything up. I think that the commissioner’s comments in support of the biosimilar pathway are important to hear, and it’s great to see that the head official at the FDA is supportive of this pathway that obviously was implemented in a different administration. I think that the commissioner and his deputies will continue to support the pathway, and I can certainly envision, down the road, that we’ll learn things that we don’t know right now. We are 7 years in with 7 approved products, and only 3 launched. So, I think we’re in our infancy and we won’t see any type of policy like this, but I do think Commissioner Scott Gottlieb is focused on lowering drug prices. We certainly, as a manufacturer, believe biosimilars is one part of the solution for that.

 Do you expect the FDA’s recent announcement of a new alignment between the Center for Drug Evaluation and Research and the Office of Regulatory Affairs to speed up the process of drug approvals?

 I think internal alignment in the FDA is probably always beneficial. I think that the FDA has a very wide purview on what they manage. Of course, drugs are a big part of it, and that’s certainly the part that people pay a lot of attention to. So, I think internal alignment and removing some of the backlog that we’ve seen in generic approvals is important. Again, I don’t know how much of that applies to biosimilars, given the infancy and also given the complexity of biologics, quite frankly. But, I do think improved alignment is probably always best for patients to be able to get more competitively priced products that are safe and effective, and the FDA is doing their job in that way.

Our goal here seems to be to improve the public health response to keep pace with acceleration and scientific innovation in a way that establishes modern legal authorities and also allows for global expansion of markets. At the American College of Rheumatology, we’re excited about anything that will speed safe and effective drugs into the marketplace, because it lowers cost and increases access. So, we’re excited to see Commissioner Scott Gottlieb leading some innovative concepts. This kind of intracenter, or intraagency cooperation is probably going to be helpful, especially because we’ve noticed that there are a lot of positions that the FDA has unfilled. It is sometimes difficult to hire the experts that are needed to issue the guidance and approve the drugs. So, this kind of innovation can only be helpful in getting drugs out of the pipeline and into the marketplace.

 I’ll also just comment, though—I don’t know how much faster things will get. I often say that things are slow, but the FDA has actually been pretty good about getting NDAs [new drug applications] approved. According to the FDA, in 2016, there were 159 more ANDA approvals than in 2015; and 242 more NDA approvals than in 2014. The fact of the matter is, NDA approvals are actually getting through the FDA relatively quickly, so I’m not sure if it’s really necessary to make it any faster. Obviously, the safety and efficacy portion is what we really care about.

Reforms at the FDA Level

 Let’s turn to the commercial market. I think this is an interesting area where we’re seeing some dynamics between plans and reference manufacturers. What we’ve seen is that some of the health plans are bypassing the adoption of biosimilars on their formularies because they have had favorable contracting relationships with the reference product sponsors. Let’s talk about that a little bit. Let’s talk about what the implications of that could be—first, from how the federal agencies might react to this. Is this something that the FDA or the Federal Trade Commission (FTC) could view as an anti-competitive relationship between manufacturers and plants?

 That’s a really well-timed question, Amanda. Just yesterday,* Pfizer sued Johnson & Johnson (J&J), in district court, alleging that the contracts and rebates with the insurers and providers for Remicade are anticompetitive under the antitrust laws. And essentially, what we have there is J&J offering rebates to insurers for Remicade in order to not have contractual commitments with Inflectra. What they’re saying is, “If you want to get these rebates, then don’t cover the biosimilar.”

The question is, is that anticompetitive? Although it sounds, in high-level context, that it might be, the fact of the matter is that J&J has come out and said, “Listen, what we’re doing is we’re providing Remicade to what’s called an ‘economically uncontestable group.’ So, it’s a group of people who are already taking Remicade and they’re not going to switch to anything else. They’re going to continue taking it, so it doesn’t really matter.” And, “The portion that’s contestable is not really that big of a deal. That’s just new patients taking infliximab therapy.” But it could be. Pfizer is alleging that J&J is leveraging the incontestable demand in order to lock up the contestable demand. They’re trying to get the new patients, too, by making sure that health plans are not going to cover Inflectra, the biosimilar.

It’s unclear what’s going to happen. The complaint was just filed. We don’t know what J&J is going to say about it. Certainly, it will be very, very interesting. Part of this is a discussion that this might just naturally be out of the fact that it’s a biosimilar and not an interchangeable. The fact is, biosimilars need to be specifically prescribed, and if that makes the demand for the innovator biologics incontestable, then is that really the market power that the FTC is looking to kind of curtail where it’s unclear?

 Dr. Worthing, how could something like this affect your patients and their access to these products? What are you concerns there?

 We’ve got a lot of concerns. The way that the system is currently working, it appears like a biosimilar manufacturer who is trying to get into the marketplace needs to contract with a pharmacy benefits manager (PBM). The way that this is working brings up a lot of concerns. As we’re talking about, here, today, the purpose of biosimilars is to try to reduce cost and increase access to drugs. But the way a pharmacy benefits management company designs formularies for payers appears to be that there is an extraction or payment system of rebates and fees from manufacturers (on the one hand) and payers or pharmacies (on the other hand). That fee or rebate is a combination of the list price multiplied by rebate percentage, multiplied by the market share. And so, if a biosimilar doesn’t have much market share, yet, because it’s a new drug, they could offer a higher rebate percentage or they could raise their list price in order to get on that formulary and pay the PBM.

And so, it’s concerning that there appear to be these incentives to increase price and increase rebate percentages in order to get on a formulary. The way the system appears to work, it might actually disrupt or prevent the process of biosimilars reducing costs. What does this mean to patients? It appears that if a patient is paying a co-payment or a coinsurance on their drug, the way the system is set up, they may actually pay a percentage of the list price as opposed to the discounted or rebated price. To some people, this seems to be unfair. Or, because of this rebating process, they might just not have access to the drug that the prescription is written for in the first place. The American College of Rheumatology that I represent has a lot of concerns about this, and we’re happy to be educating stakeholders and talking about this in the public forum.

Biosimilars, Formularies, Contracting, and PBMs

 Molly, if what we have talked about is set in place and it’s hard for a patient to have coverage for a biosimilar, what effect could there be for the formulary placement of biosimilars and reference products, downstream? How do you get your product adopted by providers? What do you do? Who actually drives that uptake?

 It’s a great question. I think we believe that health plans play an important role, certainly. They make formulary decisions—good, bad, or indifferent. I think the challenge of biosimilars is that what we’re really trying to do is help bend the cost curve and be a part of the solution for high cost specialty drugs. They’re high cost to all stakeholders. They’re high cost, certainly, to patients (as we know). They’re also high cost to health plans and employers. So, there has to be some support from the payer community as well as the physician community, and, certainly, patients who we want to buy into the promise of biosimilars. But we will need payers to be willing to push biosimilars.

It really comes down to the long-term sustainability of the market. If the first few biosimilars that are on the market as approved, are coming to the market, or whatever their status may be, if they can’t get the type of uptake that really does start to bend the cost curve, I think all stakeholders will grow tired of the hope. I think physicians will say, “This isn’t really helping my patients.” I think patients, if they don’t see a change in their cost share, will grow tired of it. And I think this will also affect the manufacturers who are investing a great deal of money in biosimilars. They are significantly more expensive than bringing a small molecule generic to the market. And they are much timelier. I think that you will see that the sustainability of the market in the United States will start to wane. I don’t think that’s good for any stakeholder, so I think it’s probably all about finding the right balance. To Angus’s point, we want to make sure that physicians are driving treatment choice and making decisions on what’s most appropriate. But at the same time, for the patient in whom a biosimilar is appropriate, and certainly when we hopefully see interchangeable biosimilars, we’ll start to see even more utilization.

I caution that we are in the early days. We have 3 products launched. No single defined the success of the generic market on the first couple of products, so I think we have to give the market some time. But I think it’s also fair to acknowledge that payers, health plans, and pharmacy benefit managers all play an important role and are important stakeholders in this, just as physicians and patients are.

Biosimilar Uptake and Health Plans

 What I find interesting about the biosimilars market is, you’ve got this whole concept of what products are placed in formulary. Then, on the actual use of the products and billing and claims processing, you have a whole other issue, which I’d like to talk about next. In addition to concerns around how private payers are going to put these products on formulary, you also have a lot of concerns with the actual billing and coding policy for biosimilars.

As all of you are aware, CMS (Centers for Medicare & Medicaid Services) has finalized its policy that says that all biosimilars to a reference product will be grouped into their own billing code, and that will be separate from the reference product. In addition, for the biosimilar, when you, as a provider, bill for a service, you will put the code for the biosimilar. Then, you have to add a 2-digit modifier that specifies the manufacturer of the product. It’s a random modifier code. This is a totally different policy than anyone has ever seen before with the billing guidelines from CMS, and the use the of the modifier for an actual manufacturer is unprecedented.

Above and beyond what you’re looking at with formulary placement, how could actual implementation of a coding and payment policy affect provider willingness to use these products—if there are any concerns around claims processing and timely payments and, ultimately, the uptake in the development of these products?

 The American College of Rheumatology would actually like this specific policy to be changed, and we’ve said that to CMS in our comments. When a provider or group or hospital has a patient that they’re taking care of and wants to provide a specific drug, it’s pretty important for the doctor, for example, to be able to provide that drug to the patient on an individual basis. One theoretical biosimilar in a family costs more for that doctor or hospital to purchase, compared with another biosimilar in that reference product family. But, if it’s the right drug for that patient, there’s pressure because of the system for that provider or group not to provide that drug. Financially, it might not be viable. It might lose money, and you might have to switch that patient to a different site of service—perhaps make them drive farther to get a hospital-based infusion or switch to the cheaper drug. That system should switch to having each drug be reimbursed on its own merits, based on its own cost. Additionally, it’s important for a drug to have its own code. A lot of doctors and systems track which drugs people receive based on that code. And so, having an individualized code would be very helpful for pharmacovigilance and for tracking what people are taking.

 Do you think the modifier code meets that, or do you think that adds more of an administrative burden versus “Here’s the separate code”?

 I’ll believe it when I see it, but it might mean that doctors would have to get to know, like you said, a very new system. They would have to track what modifier matches what drug. Again, we’ll sort of see if that system works.

 Yes, I think this raises great points from the physician perspective. I will say that from a manufacturer’s perspective, there are equally as many concerns around this blended policy. Part of the concern is that during the approval process, the FDA is reviewing each biosimilar relative to the reference product, not to one another. In other words, biosimilar A is not compared with biosimilar B. We think that putting all products on the same code kind of assumes that they are the same. Again, we’re 7 products in. We just saw the approval of the first therapeutic oncology agent, not yet marketed. It’s very early—in this market&mdash;to implement a policy that sort of equates all these products together. One thing we know about biologics is that they are different and patients react differently. That’s just the nature of the being. So, we feel like the policy is challenging in that way. It’s sort of assuming they’re all equal, and we don’t know that to be true. That’s never been proven from the regulatory agency standpoint.

The other piece is that by only putting biosimilars together in the same code, you’re half generating a competition that, I think, the agency wants to see. Fundamentally, CMS is in a bit of an unenviable position of trying to lower drug costs and trying to do things that are in their purview. That’s probably why they developed this policy, but we feel that true competition is across all products, including the innovator, too. Right now, the innovator is in its own code. And that potentially, to Angus’s point, gives more stability, from a reimbursement standpoint. Therefore, a physician may be more comfortable continuing to bill that reference product. They know the reimbursement is stable. They’ve been doing it. They don’t have to add this modifier, which is a change in process. All these things together could potentially inhibit biosimilar utilization.

Similar to what we talked about earlier, what we need to be doing now is developing policies and having a reimbursement framework that supports biosimilars and a sustainable biosimilar market. If we don’t have that, I think patients could ultimately lose out on lowering the cost of drugs and paving the way for innovation. So, we have to make sure that any policy’s coding and billing support a long-term, sustainable biosimilar market.

CMS and Blended Reimbursement Codes

 I don’t know if any of you are aware—being in the health care industry&mdash;but we have a new president who is very interested in repealing and replacing Obamacare, or the Affordable Care Act (ACA). There [have] been some really interesting, unsuccessful movements around that so far. We’ll see what happens in the coming months, but let’s talk about how biosimilars could be affected by this.

The Biologics Price Competition and Innovation Act (BPCIA) was actually part of the Affordable Care Act, but it’s not necessarily something you hear very many people talk about when they say, “Repeal and replace.” Do you think that would be a section that would be left intact if the ACA were repealed and replaced? Yes or no? And then, the other question is, if it’s intact and if you think it will stay as is, do you think Congress will address changes? Or, do you think they will punt it to the court and let the courts keep making decisions on some of the questions that have been left lingering with the BPCIA? Molly?

 I will start by saying yes, I think it will remain in place. I think that it’s clear that policy makers on both sides of the aisle want to see drug prices come down. And, I think they all recognize that the biosimilar pathway, which was part of the original Obamacare/ACA, is an important part of that. So, to date, we have not heard whether that would be in jeopardy. I don’t think that it would be, purely because of the concerns over drug pricing.

 Another reason it would probably stay is that the Congressional Budget Office might score a bill that repeals biosimilars pathways as more expensive, because Medicare and federal insurance will have to pay more without a biosimilar pathway. So, I think we’re probably all in agreement.

 Yes, I can confirm that we are in agreement on this. Honestly, the BPCIA also, from an IP (intellectual property) standpoint, forms the litigation pathway for biosimilars. And, honestly, I think it was meant to be kind of analogous to what was done of Hatch—Waxman—it kind of allows for a process to deal with IP issues prior to the product actually launching, rather than having to worry about declaratory judgment actions and preliminary injunctions and all this messy stuff in the courts that nobody wants to be involved in. So, why not get it done early? I think the problem is that there are a lot of loopholes there. There are a lot of issue there, but I certainly think that the BPCIA will stay intact.

 Do you think we’ll see changes to it added in, or do you think they’ll let the courts decide as things come up?

 I am of the mind that the courts still have a couple of questions to answer. Right now, as it stands, after Sandoz v Amgen, the entire litigation pathway is optional. That is a little bit of an issue, because I suspect that Congress didn’t spend all that time drafting a statue to be a convoluted pathway to litigation that was meant to be not only optional but fully in the hands of the biosimilar manufacturer. In the Sandoz v Amgen case, the Supreme Court actually came down on this. They basically said that there really is no remedy if you don’t take the first step. And the first step was, after the biosimilar applicant actually filed the application, they were supposed to supply that to the reference product sponsor, along with manufacturing information, within 20 days. The big question was, “What happens if I don’t do that as a biosimilar manufacturer?” And the answer from the Supreme Court is, “Tough luck—go sue them.” And that’s what will happen. You’ll have to bring a declaratory judgment action. So, you might think from the outside, That’s fine. They still have a remedy. They can still go to the courts. But, the fact of the matter is that the BPCIA litigation pathway was meant to narrow down the IP so that you could focus on the aspects of what should be challenged now and what should be challenged later.

As we’ve talked about, biosimilars and biologics are so much more complex than small molecules, and they have so much more IP. If you look at a typical 

—listed small molecule product, maybe you have 1, 2, or 3 patents. And outside, maybe you have 10, but that’s a very rare thing nowadays. But biosimilars and biologics—you can have 50, 60, 70, 80 patents and all different aspects of it. And, of course, the products are not exact copies because they’re made from living cells. So, infringement is an issue.

So, how do you narrow all that stuff down and do this in an orderly way? Well, Congress thought BPCIA would address that. But, now that it’s optional, it makes it a little bit of the Wild West again. I think that is an issue, and I wouldn’t be surprised if Congress wanted to revisit that—if they had the opportunity.

 I have another ACA question. The Independent Payment Advisory Board (IPAB) has not been the most popular policy on either side of the aisle. Can you all talk a little bit about the IPAB? What are they all about? Why does everyone want to get rid of it?

 Sure. The Independent Payment Advisory Board, IPAB, is not yet in place. It’s what would be an unelected board that would report to Congress with suggestions on how to tamp down Medicare expenditures if the system grows to be too expensive. A lot of provider groups are against IPAB, and there’s a lot of support in Congress to take that piece out and control costs in different ways.

As a rheumatologist and an internist taking care of patients for the last 20 years under a different system before the IPAB, I saw that doctors essentially didn’t get raises in their reimbursement for taking care of patients in the Medicare system to cover the cost of inflation in rent, payroll, and health insurance for their employees. What you saw was that a lot of doctors left the Medicare system or left insurance in general. They started taking cash payments from patients. And so, it leads to this point today, where one of the hardest questions I get from patients in a rheumatology clinic, who have arthritis and rheumatologic diseases, is not about a patient’s specific condition but, rather, it’s the simple question of “Can you refer me to a good primary care doctor that takes Medicare?” It’s really hard. So, with IPAB, we see the possibility where that board might reduce payments even further to physicians. This may make it harder to stay in practice and take care of people in the Medicare system. And so, we’d rather see a different way.

Healthcare Reform Efforts and the BPCIA

 Let’s talk about the state level. A majority of states—I think we’re up to 33 now&mdash;have enacted laws concerning the substitution of biosimilars for reference products. I know that state pharmacy boards and states work together and put laws out all the time. How do these laws differ from what you traditionally see? Have they gone above and beyond? Are they doing what you’re hoping they’re going to do for biosimilar products?

 After the Affordable Care Act was passed and we had a biosimilar pathway, there was the realization that we had 50 state laws plus a couple of territories that we had to update to actually allow for substitution.

 Yes, and the District of Columbia. When you pass a federal law, you think, this is great. The FDA is going to approve biosimilars, and patients are going to get them. The reality is, pharmacy laws reside within the state. And so, we have seen to date, as you mentioned, that the majority of states now have laws. But, we had to do the same thing back in the 1980s over Hatch Waxman. So, there is this idea that we implement these laws that essentially allow for the automatic substitution of interchangeable biosimilars. I think that’s an important distinction. As we talked about regarding interchangeability earlier, we are building substitution laws based on that additional layer of designation from the FDA and study by the manufacturer. 

You’ve seen different challenges in states. The physician notification piece has probably been the most controversial and the biggest sticking point in terms of how soon after a substitution you are required to communicate that back to the physician. The physician knows which product they have. The patient notification happens when the patient gets the product, but the physician piece is the sticking point. You’ve seen some states implement as soon as 24 hours, and you’ve seen other states be more in the 3-to-5-day range.

The truth is, it’s quicker than small molecule generics. I think that speaks to the complexity of these products, but I think we have a little ways to go in terms of getting all the states to update them. I think that with some of the uniformity issues, as time moves on and we see interchangeable products, we could see a situation where, from a pharmacy perspective, maybe the 24-hour notification is too quick— and maybe, from the physician perspective, 5 days is too long? We will see. We’ll have some lessons on what the right thing is, and we’ll probably need to go back and revisit some of them. The most important thing is to make sure that no matter where a patient lives, they are able to get an interchangeable biosimilar substituted if that’s the appropriate choice for them. It’s an important topic. It may be a little bit of a weedy topic&mdash;when you think about biosimilars&mdash;but it is very critical.

 I agree. Notification is the big piece in the state substitution laws. The American College of Rheumatology really wants the patient and the doctor to be as closely involved as possible at that moment, when somebody is moving from a reference product to a biosimilar. From the position of the American College of Rheumatology, the doctor should write the prescription when they’re changing to a biosimilar. However, in states where it’s legal for a pharmacist to substitute a biosimilar, the American College of Rheumatology—and I think a lot of doctors&mdash;want to know right away that the substitution has been made. The reason is, we’re treating complex diseases and we’re using complex drugs. Patients might be giving themselves a shot of one of these drugs every week or even twice a week. The number of days makes a difference if somebody is taking a drug every 3 or 4 days. When a doctor finds out only a week later, that’s too long. But 5 days might be short enough.

 Are any states popping out as interesting case studies on biosimilars?

 I would say 1 thing, and this is not really in my area as IP but is actually in the area of cost. We notice that some states—Colorado, Georgia, Illinois, North Carolina, and Texas&mdash;are requiring that the interchangeable biosimilar must have the lowest cost. I think it’s a little tricky. As we saw in the Orange Book space, Hatch-Waxman space, and small molecule space, is it really lowest up-front cost or lowest net cost? Or what are we really talking about? You have rebates. You have discounts. You have things that don’t appear up front. It can make it really tricky, unless they want to get into a real economic analysis as to what lowest cost means. I don’t know if anybody has any thoughts on that?

 Well, I wonder if you think that will increase the amount of transparency in those states? What do you think, Ha Kung?

 It’s unclear to me if it will. To some extent, I think that it will require people to say something about it, but how they actually characterize lowest cost is a tough thing to do. I’m not an economist, but I’m sure most economists can call something that’s $10 more “lower cost” in some way. It’s a tough thing, so I think, yes, perhaps there can be some more transparency, but I think it leaves a lot of room for a lot of ambiguity.

 You raise an interesting point. I’ve had the pleasure of working on some of the language and the specificity, and I think the question around “lower cost to whom” is a critical one—in the broad drug-pricing debate but, certainly, in these bills. I think it’s typically to the patient. So, what is their actual cost share, and how does it ring up at the pharmacy level? That type of language may end up being something that, in hindsight, works really well&mdash;to ensure that the patient, based on their benefit design and plan, really is getting the lowest out-of-pocket cost for them. It could also be that we see that it’s something that was written in with really good intentions, but it’s actually very difficult to execute. Right now, we’re a little bit in the unknown. We don’t have any interchangeable products yet. But, I do think that’s an important question and is potentially one of those areas where we make laws for what we know now. They don’t always reflect what the market actually looks like.

State Laws and Biosimilar Substitution

 Let’s move on and talk about biosimilars and litigation. The Patent Trial and Appeal Board (PTAB) has been playing a role in patent disputes over biologics and biosimilars. This role has been growing. What is the PTAB, Ha Kung? Can you give us some information on that? Why is it becoming increasingly involved in patent disputes over these products?

 Contrary to popular belief, it’s not a low-caloric drink from the 1970s. It actually is a trial court in the PTO (Patent and Trademark Office). It hears and decides contested proceedings and other things. It came about from the Leahy—Smith America Invents Act (AIA). The AIA was passed into law in September of 2011. It kind of created 2 different types of contested proceedings that are interesting to us in biosimilars— the IPR process, which is the inter partes review, and the PGR process, which is the post grant review.

The interesting thing about this is that it allows for someone to challenge patents outside of the court system. You might think, Do we really need another venue for that? And at least for the AIA, the answer was yes. They shifted the balance a little bit when they created these processes. There are a number of things that are different than when you go into litigation. When you go into litigation with a patent, you have a presumption of validity. If you go into the PTAB, you have no presumption of validity. They start from a neutral stance. And when you go into the PTAB, there’s a lower burden to proving invalidity. You only have to show “by preponderance of the evidence”—so, 51%. That will get you an invalid patent. It will allow you to invalidate a patent. In a district court, it’s what I call 70%, but it’s clear and convincing evidence&mdash;somewhere around 70%, 75%. So, there is a significant gap there. You can be invalid in the PTAB but not invalid in district court. We’ve seen that. The Federal Circuit and the Supreme Court have looked at that, and they’ve deferred to the PTAB. So, this is a very dangerous thing for patent owners, and we’ve seen that play out over time.

The other aspect of the IPR and PGR process is that they’re both statutorily limited to 18 months, from the date of the petition to the final decision. Now, that may sound like a long time, but litigation can take a long time—usually more than 18 months. This is a very short time period. And, more importantly, it’s limited to just invalidity. There are no infringement issues. So, as a patent holder, you have no ability to raise any issues concerning infringement of a new product that’s coming in the market. And 1 step further than that, you don’t even need to have standing. Anybody can do it. I could do it, you could do it, anybody could do it. You could just walk in and say “I want to challenge that patent,” and we’ve seen that. We’ve seen that from a number of hedge fund managers who’ve come in and tried to manipulate the stock price by filing a bunch of IPRs against patents that are owned by pharmaceutical companies.

It is a little bit of a dangerous area. At the beginning, there were a lot of IPRs coming through the PTAB. The cancellation rate was astronomical. Up to 80%, 90% of claims that were challenged were being cancelled in the PTAB. The former chief Federal Circuit judge, Randall Rader, actually called it the death squad. Any patent that went in there was basically not going to get out unscathed. Now, along the biosimilar path, we haven’t seen as many of these IPRs, yet. They’re starting to grow. In 2015, there were about 10. In 2016, there were maybe 10 or 11. In 2017, we’ve seen over 3 times that number already, to date. So, this is exploding, as far as biosimilars and biologics are concerned.

What does that really mean for biosimilar patents? That’s kind of yet to be determined. We’re not really sure. When you look at the overall numbers, the cancellation rates have started to come back in line with what you want. They’re down to around 60% for all technologies, and for the 

, small molecule technologies, they’re about 50/50. And then, in the biologics and biosimilar space—and this is for a very small sample size&mdash;they’re about 50/50, as well. This could mean that life science patents are just generally harder to invalidate because of the unpredictability of the science as compared to the electrical and mechanical fields, but it’s unclear. What we do know is that there are 30 biosimilar IPRs currently pending. And with the short time frame, they are going to get decided on soon. We are going to have a lot more data. I got a lot of these data from biologicshq.com, which follows the statistics. The numbers are small now, but after those decisions come out, I think we’re going to know a lot more about it.

The PTAB's Role in Biosimilar Patent Disputes

 Back in June, the Supreme Court made a ruling on the case of 

, which clarified some issues around the so-called BPCIA (Biologics Price Competition and Innovation Act) “patent dance.” This has left some other questions unanswered. What clarifications are biosimilar developers looking for now? What did they get from that? And, what about innovators?

 We talked a little bit about this earlier. The 2 aspects of the “patent dance,” as we call it, and this BPCIA litigation pathway for biosimilars that was impacted by the Supreme Court decision was, first of all, the aspect of, what happens if you don’t give them the biosimilar application? The second part of it was, what happens with the 2 lists of patents that you narrow down to in this pathway? In one, you litigate right away. The other one is keyed off with this commercial manufacturing notice. That question was kind of answered by the Supreme Court. They can actually give that notice any time they want, even if it’s not an FDA approved product. So, I’ll put that aside.

The real question that people are looking for clarification on is, what has to be done in order to get the BPCIA process going? Right now, it looks like it may be optional. There is one aspect of it that was remanded back to the Federal Circuit, and that was whether state law injunctions can be used to enforce the BPCIA. All the Supreme Court said was that federal injunctions can’t be used. So, that is a question. And then, the second question is, if so, is it preempted? The United States actually filed a brief saying, “Yes, it’s preempted.” Clearly, they think they preempt everything, so it’s not really a surprise. But, it will be something that people will look at, pretty carefully, to see if there is still life in the BPCIA litigation pathway.

And the second aspect is, we talked about total noncompliance. “I’m not going to give you the application.” “I’m not going to give you my manufacturing information.” “Come sue me.” But what happens if I just give you the application and I don’t give you the manufacturing information? So, let’s say “partial noncompliance.” Well, so far, it looks like according to 

, and some other things we’ve seen, that you’re left with the same problem. “You don’t get to start the BPCIA pathway.” “Go sue me.” They go and get a declaratory judgment action. So, again, Congress’s intent, I think, was thwarted. You kind of see the ambiguity in the language and the statute.

Let’s talk about an even stickier situation. What does manufacturing information mean? “How much do I have to give?” “I don’t know.” So, maybe I, as a biosimilar manufacturer, gave my application. I gave my manufacturing information, but it’s not enough. Does that mean that I have to get sued? Or, does that mean I get to go into the BPCIA pathway? Who knows. Those are all open questions. A lot of people are looking for clarification. I’m not sure that the courts are going to be able to clarify it. It might come down to Congress.

 I appreciate your talking about the “patent dance” a little bit, Ha Kung. As a rheumatologist taking care of people, what was meaningful to me was the first part where you mentioned that because it’s now simple and you put it aside, the notification can start at any time, which means that I’ll learn about a drug when it’s FDA approved, generally. It will entice patients and doctors to find out more information about it. And the sooner that that drug can be available after the FDA approval date, the better to improve communication and education. And then, it’s also refreshing that the marketplace is working and the drugs can come out quicker and safer.

 The interesting point, here, is that the reason why biosimilars wanted to give notice early was not because they wanted to market the drug earlier. It’s because they wanted to trigger the litigation on a second set of patents, earlier. So, it was actually kind of looking at ways to manipulate the statute to trigger more litigation, earlier. That’s not necessarily a bad thing. I’m just saying that when you say, “I’m going to give 180-day commercial marketing notice,” you’d think that you’d have something to commercially market. You can’t just say, “Hey guys, I plan to make this drug sometime in the future. Here’s your notice. I’m going to market it someday.” But the Court said, “That’s okay.” So, it’s okay.

The Need for Clarity After <i>Sandoz v Amgen</i>

We talked earlier about the Pfizer lawsuit against Johnson & Johnson. What other litigation should we be looking toward in the coming months as an industry?

 Every “patent geek” out there is looking at the pending Supreme Court case with Oil States Energy Services. The reason is, Oil States is looking at whether the IPR (inter partes review) process is even constitutional. The fact of the matter is, they’re looking at whether patents are considered private property. And if it’s private property, whether it can be extinguished by anything other than an Article III court. If that’s the case, that it can’t be extinguished by anything but an Article III court. Then, the PTAB (Patent Trial and Appeal Board), being a regulatory agency, so to speak, can’t do it. That means that everything that we’ve seen cancelled in the last 5 to 6 years, suddenly pops back to life. That would be very interesting. That would change the dynamic of IP (intellectual property) litigation, dramatically. A lot of challengers have been looking to this IPR process in the PTAB, in lieu of litigation, because it’s cheaper and faster. If that goes away, not only will we suddenly have all of these patents that are now back as invalid, but it will change the way people move forward in the future, as well.

The other case that I will mention is that there’s an Amgen-Sanofi case that looks at the use of permanent injunctions in drug patent disputes. I think it will be interesting to see how that turns out, because it will significantly impact biosimilar applicants and whether they want an at-risk launch or not, assuming that the regulatory exclusivity has already been completed. And then, the 

 case actually talks about whether the ramp up and making of the product, and warehousing of the biosimilar product in advance of launching it is something that’s under safe harbor or not. The question there is whether safe harbor actually applies to commercial batches of a biosimilar that’s prepared prior to launch. And in that case, Hospira has manufactured over 20 million doses with a commercial value of hundreds of millions of dollars. They say, “It’s solely for uses reasonably related to the development and submission of information to the FDA. So, therefore, it’s safe harbored.” But is it? I don’t know. And if it isn’t, that could be significantly damaging.

 Dr. Worthing, let’s talk a little bit about all of the litigation and the complexities around that. The bottom line is patient access, right? Ultimately, you want to get patients to products faster. You want to give safe products as soon as possible. What are the concerns, not just with this patent litigation, but other cases you see coming to market around anticompetitive behavior? What is the ultimate effect for that on your patient population?

 Well, to tell you the truth, we don’t talk too much about lawsuits in the clinic. But the overall effect of a delay in the courts or in litigation, of which I have learned a lot about on this panel, I appreciate. The net effect of all of that is that there’s a delay in getting drugs that might be cheaper. People might have an easier time getting control of their disease, their aching joints, and their other organs that might be inflamed. I’ll just register that there’s a little bit of frustration about it. Doctors appreciate the innovation that helps us, and the tools that we can use to take care of patients. But I think a lot of us want to just see the new drugs come out, so that we can use them, if they’re safe and effective, and meet our bar.

 How many of your patients are walking in your office knowing what a biosimilar is, or are following this? What percent of your patients actually know that Inflectra (infliximab) is available? Or, that Renflexis (infliximab-abda) is coming out and could be a potential therapy for them to switch over to?

 Good question. I have the pleasure of practicing in Washington, DC, downtown on K Street. A lot of people are actually involved in the healthcare business and in policy. Some of them are actually people who know a lot about biosimilars, or even more than me. But for the average patient, I’m taking some extra time in a lot of my visits to tell people who are taking a biologic about what a biosimilar is and a little bit about the marketplace. Then, they know. They might do some research—if they’re interested when the time comes or when we might be deciding, together, to move to a biosimilar. But not too many people have heard about them.

 Let me add one thing in respect to patent litigations and its impact on consumer access to biologics. I want to make note that the BPCIA pathway, like the Hatch-Waxman pathway before it, was meant to sort out all of the IP issues prior to the approval of the generic or biosimilar. It was meant to not delay the access, but to actually be done during the regulatory stay period. In the Hatch-Waxman context, that would be the 30-month regulatory stay. In the BPCIA pathway, it would be this kind of new biologic entity, a 12-years stay on approval. In essence, although patent litigation could take a long time, what actually slows things down is not the litigation, itself. Patent litigation can be slow, but it’s usually not 8 years slow. Typically, it’s actually the regulatory exclusivity that will slow it down. After you have the 12 years, you may have another 6 months, and you can kind of go on from there.

I’m not saying that there aren’t instances in which the regulatory stay has been extinguished, and that litigation is ongoing and could cause some issues with timing. But I’m saying that in a typical process, the BPCIA was meant to actually expedite the litigation, to make sure it’s done early on, so it doesn’t slow the access of the biosimilar to the marketplace. Then, all of those IP issues are sorted out and it doesn’t end up being a situation where someone has to launch, at-risk, or go for a preliminary injunction.

Upcoming Patent Litigation in Biosimilars

 Before we wrap up our discussion, I’m just going to take a lap around the table and see if anyone has any final comments to share. Molly?

 I think that this has been a great discussion. I think the biosimilar pathway holds a lot of promise for the United States in terms of patient access and hopefully lowering costs. But this discussion shows the complexity and the challenges that we have ahead of us. I think that this is an area where our friends in Europe are ahead of us. They’ve had biosimilars available for the last 11 years, somewhere around 700 million patient days. We have a long way to go in terms of seeing more products hit the market and seeing the impact on spend and patient cost share. It’s an exciting time in the United States, to see a brand-new market really start to develop. So, we remain cautiously optimistic that stakeholders, physicians, patients, and policy makers will continue to see the value and support long-term and sustainable biosimilar markets. It’s an exciting time.

 Biologics have truly revolutionized the care of diseases like rheumatoid arthritis and other autoimmune diseases. The purpose of biosimilars is to reduce the cost, which, unfortunately, is very high right now, and improve access to these great drugs. I look at the chance that biosimilars might not realize that promise and keep that promise. For example, the distribution system and other issues that might come up in terms of confidence in prescribing if this doesn’t work out; and it reminds me of when Y2K was happening for people who were using a computer and all of the work that had to go into making sure there was this seamless transition to the new millennium. Right now, we’re doing that kind of work in biosimilars.

I’m very grateful for being on this panel and having the ability to communicate my views. I’m also grateful for all of the different stakeholders: the manufacturers that are creating these products, the government lawmakers and regulators who are approving and regulating the distribution of these products, and, ultimately, my fellow physicians and all of the patients who are learning about them, prescribing, and taking them, so that we can also have that seamless transition to a time when they’re less expensive and everybody who needs them has access to them.

 Biologics are definitely the future of medicine. Small molecules will always be there, based on their ability to synthesize compounds and screen for activity. But biologics are essentially untapped. It’s like science fiction. We never thought we’d get to this point. But what that means is that we’re going to see many, many, many growing pains with biologics. We’re going to see more of the growing pains with biologics than we saw with small molecules, including optimizing paths to innovation as well as protecting the innovation of IP (intellectual property).

One of the major differences between small molecules and biologics is that there’s a significant increase in unpredictability that researchers are faced with due to the complex structures of those compounds as well as the method in which they are produced. Because of this, there is a much higher barrier to entry for any research entity to develop viable patient treatments out of biologics. And this resource commitment will, in turn, increase the amount of IP obtained, particularly in light of the fact that the United States is now a first-to-file system. People are racing to the patent office to get their inventions on file, as well as to increase the amount of IP challenges in part due to the IPR (inter partes review) and PGR (post grant review) process that we talked about. More than ever, researchers will have to be vigilant about their biologics development, not only for the safety and unpredictability issues in the science, but also in the way and manner in which they seek protection for their ideas and research. It’s going to be a really interesting ride, but everybody better keep their eyes on the road because we can only guess what that road is going to look like.

 Those were really great sets of insights from 3 very different perspectives. I really appreciate all of that. Thank you all so much for your contributions to the discussion today. On behalf of our panel, we thank you for joining us and hope you found this Peer Exchange

 discussion to be useful and informative.

Regulation, Policy, and Litigation in Biosimilars