Are there some emerging directions in treating inflammatory disease that you’re particularly excited about?

I think the area that we most need to work on is trying to figure out which patients do the best on which therapies. Some patients do very well the first thing you use, but we’ve all had experience with patients who need to cycle through a variety of medications before we find the 1 or the combination medicines that works just right for them. It would be wonderful if we had a test from the beginning that could tell us that we need to target 1 pathway and 1 patient, and a different pathway and a different patient. We’re not there yet, but that’s certainly a direction that we’re moving in as we begin to understand these diseases on a deeper level pathogenetically.

Videos

Anne Bass, MD, rheumatologist at the Hospital for Special Surgery and professor of clinical medicine at Weill Cornell Medicine, talks about some emerging treatments in inflammatory disease.

Anne Bass, MD: Emerging Treatments in Inflammatory Disease

Immune checkpoint inhibition for cancer therapy can result in musculoskeletal adverse events, how are these adverse effects treated in the rheumatology clinic?

So, this is a really exciting area because these immunotherapies are prolonging the lives of people with metastatic cancer who had otherwise would’ve died. They work by stimulating the immune system and allowing it to target the cancer. Not surprisingly, when you stimulate the immune system, you can cause autoimmune diseases; and that’s what we’re seeing and they take many shapes and forms. Some of the earliest ones we knew about were immunity in the skin and colitis involving the gastrointestinal track, but as time has gone on we’ve come to realize that some of these patients— probably about 5%– develop an inflammatory arthritis and it can take, again, many forms.

I think one of the reasons there was a little delay in recognition is that it may be a little bit more common with some of the newer immunotherapies that target PD-1 and PD-L1 as compared to the older therapies with CTLA4 blockers, and it's seen particularly [common] when you use those 2 groups in combination. So, patients will come to a rheumatologist as they would if they had inflammatory arthritis that developed in some other context and these patients have all different kinds of presentations. Some of them have zero-positive rheumatoid arthritis that looks for all the world like rheumatoid arthritis, others have fewer joints affected, or they have tendons that are swollen. We’ve seen polymyalgia rheumatica, and their case is almost of every rheumatic disease you can think of with these checkpoint inhibitors. There are many fewer cases of things like lupus and drama monocytes though than there are of patients with rheumatoid arthritis, psoriatic arthritis, and the inflammatory rhinitis in general. 

Anne Bass, MD, rheumatologist at the Hospital for Special Surgery and professor of clinical medicine at Weill Cornell Medicine, discusses how rheumatologists treat musculoskeletal adverse events caused by immune checkpoint inhibitors.

Anne Bass, MD: Immune Checkpoint Inhibitors in Rheumatic Disease

When will we see price competition on biosimilars?

I think if you think of it in a purely economic, capitalistic sense then you should expect, like [with] generics, with 3 [biosimilars on the market] it’s enough competition to bring that down. But, again, there’s other considerations in predicting how much of an impact that will [have]. In Europe they are seeing significant costs and influences, but they also have multiple products per category, for the most part, and they have a healthcare structure that’s quite a bit different and quite a bit more linear and a bit simpler than what we face in the United States. Here, there’s contracting and rebates, and all of these other components that go into pricing that I think becomes more of a challenge and harder to predict. At least my perspective is that you really have to think more broadly, you have to think longitudinally and not quarterly, “This is my bottom line this quarter,” but looking more longitudinally about say, [if] I’m a payer or a physician, ultimately, what’s going to be the best for the patients, including their costs as well as their treatment. 

Now if we assume, like we’re saying that biosimilars really are clinically no different, then thinking about some of those other considerations is important for our patients. Again, it comes down to having evidence to support that, to trust the biosimilars. 

Cate Lockhart, PharmD, PhD, discusses when she believes the industry will start seeing biosimilars driving down cost of drugs. 

Cate Lockhart, PharmD, PhD: Biosimilars and Price Competition

What are some ways in which biosimilars are like generics?

That’s true they’re not generics, but I think what people fail to realize or fully appreciate is that “no clinically relevant” difference. So, my PhD is in pharmaceutics so from a pharmacokinetics stand point a biologic— the innovator biologic– has quite a lot of variation within a single batch from lot to lot. But there’s really– you can keep taking that same innovator biologic, even though it’s going to be a little different than the last dose that you had, probably, or there’s a risk or chance there would be some level of variation. It’s probably not a lot of variation, but it is there, and you don’t see a clinically different response. 

It’s the same story with biosimilars. There’s going to be variation, there’s going to be variation within the biosimilar lot. There’s going to be variation between it and the reference product to some extent within the threshold, but the exact same thing is true with generic drugs. There’s less variability within a lot in generic drugs, but the variation between the original branded small molecule drug and the generic is still within the threshold. So, it’s not identical ultimately, [but] there is a threshold and it’s really the same story with biologics that there’s variation anyway, but it doesn’t manifest itself in any clinically relevant way. 

 

Cate Lockhart, PharmD, PhD, explains the similarities and differences between generics and biosimilars.
 


Cate Lockhart, PharmD, PhD: Similarities Between Biosimilars and Generics

So at Sandoz we're just so thrilled with the experience. We have 20 years' worth of experience in biologics, 340 million patient days of exposures to biosimilars in 86 countries. We are so excited for the value that we can bring to Americans. They so deserve getting access to these important products, both from us and from our industry colleagues, in order to free up capacity for the new innovations that are coming, but also, and importantly, to get the benefit of the savings and increased access that they'll have.

Sheila Frame, vice president and head of biopharmaceuticals, North America, at Sandoz, explains what about biosimilars excites the company. 

Sheila Frame: What Excites Sandoz About Biosimilars

I think physicians have transformed their thinking over the course of even the last 2 years. I've had the benefit of working in immunology for years, and, even if I think about what rheumatologists, for example, said 2 years ago versus what they're saying today, I think physicians are definitely ready to take a look at what the promise of biosimilars are, as long as their patients benefit from it. 

And I think that comes back to the whole challenge of transparency in the system. How does an individual patient or an individual infuser, physician infuser, benefit from the value that biosimilars bring into this marketplace?  And, you know, I think that's such a great opportunity for the United States to benefit from 15% or 20%, whatever that discount's going to be. The more competition we have then the more patients are going to benefit from not only the care that they're going to get from the biosimilar product, but also from the opportunity to enjoy access to other products as it comes in. 

Physicians specifically, I think, are almost getting to the point where they're kind of, hey, this is going to happen. It's happened everywhere else in the world. It's important to the system overall. I get it. I'm going to try it. And I think that's what we're starting to see now more and more, and certainly for Sandoz with Zarxio and our experience there, we've seen increasing excitement in the marketplace as each of these institutions have switched to Zarxio as a preferred product and continue to. We're now seeing some payers starting to take that into consideration. 

And so, once that starts to happen, then you generate US evidence to say US patients are certainly benefiting from it. The system's benefiting from it. And, from a physician perspective, as long as I can count on the safety and efficacy in my patient once I've made the choice of what the right treatment is, as long as I can count on the safety and efficacy, then I’m okay. Let's make it happen. So I think physicians are moving along that adoption curve and certainly are definitely I'm going to say inspired by the European experience and examples that we've had over time.

Sheila Frame, vice president and head of biopharmaceuticals, North America, at Sandoz, discusses how physicians' attitudes toward biosimilars have changed.

Sheila Frame: Adoption of Biosimilars

What is the role of health economics and outcomes research in a payer’s decision to potentially adopt a biosimilar?

I think, of course, health economics in outcomes research plays a huge role in these therapies. A lot of the benefits that are hopefully going to be seen from biosimilars are on the overall cost reductions that can be applied to the healthcare system through reduced costs of these therapies.

I think an important aspect here is taking a bit of a longer view in the use of these therapies. So again, as folks are looking at total cost of care, not just purely on the acquisition cost of the product, making sure the outcome is happening, the benefit is happening from the therapies. But clearly the reductions here with these agents are in the actual cost of the biosimilar and hopefully as more of these products enter the marketplace we’ll see more competition, and therefore we can see a better, bigger, cost-reduction in the therapies.

I think one of the challenges, of course now, in the market as well as is the fact and part of the reason why we’re just not seeing despite 10* of the therapies approved that we’re not seeing these therapies, more than 3 marketed, is there’s a lot of patent litigation going on. And there are also agreements between the manufactures, some pay-to-delay of these therapies to hit the market. So hopefully, as we can get past those issues and get more of these therapies available we’ll see the benefits in the marketplace.

Mark Cziraky, PharmD, CLS, explains the role of health economics and outcomes research in a payer’s decision to potentially adopt a biosimilar.

Mark Cziraky, PharmD, CLS: Payers' Decisions on Biosimilars

So I think the whole issue of switching stable patients certainly continues to be the highlight of many debates, both for physicians as well as for associations and patient groups.

And so I do think it's something that certainly at Sandoz we take very seriously. I do think though, you know, if you think about a patient who's been well controlled on an originator product, they've already been subjected to biosimilar switching. Every batch that they've had over whatever period of time has been a biosimilar.

And so I think that they're—I totally support and understand what the concern would be. Don't mess with my&mdash;especially if you're subjected to pain. Nobody wants to go back to that world when you talk to some of these patients and the patient associations. You just wouldn't want to put anybody through that.

At the same time, given the requirements under the [Biologics Price Competition and Innovation Act, BPCIA], I think also just what we actually do in order to prove the safety and efficacy, I really think it's worth a try. I really do. I think I would say to a patient, you know, be open, give it a shot, and then the value that's created in the system to free up the capacity to fund those new innovations that are coming I think is probably worth taking the chance, in the appropriate context.

I mean, I'm not a physician. So I'm not going to give medical advice, but I definitely think that given the publications and the experience, we've had years of pretty massive switches in many of the European countries, and we haven't seen any issues emerge over time. So, while, again, I understand the concern, I just think that the safety and efficacy that we've been able to prove and demonstrate with the kind of exposure that we've had is probably worth the try.

Sheila Frame, vice president and head of biopharmaceuticals, North America, at Sandoz, discusses patient concerns about switching to a biosimilar.

Sheila Frame: Switching to a Biosimilar

I think it's certainly the changes and the new regulatory pathway has certainly helped us as an industry continue to refine and move forward. I think there's some definite advantages for biosimilars in terms of what those hurdles actually are from a safety and efficacy perspective without at all compromising patient safety or what the true requirements are. I mean, the fact that we have to do comparative trials to demonstrate that there's no difference between the efficacy and safety that we have versus an originator across multiple batches, right, is pretty significant, and I think should lend a lot of credibility and confidence to the marketplace.

At the same time, I think we're still learning, right?  So, from a drug development perspective, when you're looking at these kinds of investments, which are significant, I mean, we're running clinical trials like an originator would, I think that we're looking at things like how do we use extrapolation or do we have to do these trials around interchangeability that I think the FDA's still working on. How are we going to overcome some of those kinds of challenges? 

And especially for the United States to be able to benefit from the simplicity of the European system, I think those are some of the things that we think could certainly add a great deal of policy information to speed along some of those changes. But for sure the openness in Washington right now to working with our industry to making sure that it's not a standard generic. It's not pill pressing. It is a biologic that requires the right kind of hurdles in order to make sure. And manufacturing these things, not easy, right? It's a very difficult process, and we take it very seriously. I think for Sandoz we're really lucky, because we have the benefit of our parent company as well as our own 35 years' worth of experience in this area. So we're certainly leveraging all of that, and then the openness to work with government in order to make it as smooth and as robust as we possibly can. So we're excited about the changes that have happened in the United States.

Sheila Frame, vice president and head of biopharmaceuticals, North America, at Sandoz, explains how the Biologics Price Competition and Innovation Act (BPCIA) has impacted the industry.

Sheila Frame: The BPCIA's Impact on Industry

How important are real-world data about the safety and efficacy of biosimilars?

Yeah, I think they’re extremely important; real-world evidence and using real-world data to generate real-world evidence is extremely important in this area. Just by the nature of these therapies there is potential for some concern around their effectiveness compared to the comparative agent that they’re built from. So therefore, the fact [is] that we want to get more evidence of their use in the marketplace to show that they are reaching their intended outcomes and not showing the adverse effects that we hopefully won’t see with the products in the market.

Mark Cziraky, PharmD, CLS, explains why real-world data are key in the biosimilars marketplace.

Interviews