Why are thromboembolic events a special concern for patients with rheumatic disease?

So, we’ve learned that there’s a strong connection between the immune system inflammation and the clotting system. When your immune system is active, it actually makes you more prone to clotting. When patients have rheumatic diseases—not so much when they’re quiet, but when they’re active&mdash;almost any rheumatic disease, they’re at higher risk for blood clotting. It’s particularly true of conditions like granulomatosis with polyangiitis, which we used to call Wegener’s, but it’s really been shown to be the case with any rheumatic disease, including rheumatoid arthritis, for example, where the risk is about 2 and a half times when your disease is active than it would be if you didn’t have rheumatoid arthritis.  

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Anne Bass, MD, rheumatologist at the Hospital for Special Surgery and professor of clinical medicine at Weill Cornell Medicine, explains why patients with rheumatic diseases are at risk for thromboembolism. 

Anne Bass, MD: Thromboembolic Events in Patients With Rheumatic Disease

Why is screening for tuberculosis before initiating treatment with a drug like infliximab so important?

Infliximab is a tumor necrosis factor inhibitor, and these agents interfere with the body’s ability to defend against certain kinds of infections, particularly viral infections and infections like [tuberculosis, TB].

Some people, particularly in Europe or people from the Caribbean, have been exposed to TB in the past, even if they didn’t actually have TB. A small amount of the bacteria stays latent in the lungs, and if you take a medicine like infliximab, the TB can become reactivated.

So, you want to make sure to know if they’ve been exposed to TB so that they can be given treatment, and then subsequently be able to take a medicine like infliximab.

Anne Bass, MD, rheumatologist at the Hospital for Special Surgery and professor of clinical medicine at Weill Cornell Medicine, explains why screening patients for tuberculosis before initiating biologic therapy is key. 

Anne Bass, MD: Screening for Tuberculosis Before Starting Biologics 

What are some ways that biosimilar developers can minimize uncertainty in the patent litigation process?

Sure—I’m glad you limited the question to the litigation process because in the regulatory side there is a lot of uncertainty that’s still going on. For example, just today* when it comes to Herceptin, the FDA is asking for more information before even considering the request Pfizer has made.

On the litigation side, I would focus on 2 things. One, identifying the patent landscape for the amount and number of patents that are or could be applicable and 2, identifying early experts that would be available for each of those individual patents.

Those are 2 areas where if there isn’t activity early enough, a lot of unpredictable things can happen.

Imron Aly, JD, partner at Schiff Hardin, LLP, explains how biosimilar developers can minimize uncertainty in patent litigation.

Imron Aly, JD: Minimizing Uncertainty in Biosimilar Patent Litigation

In our growing experience with the Biologics Price Competition and Innovation Act, are there some trends that you’ve seen emerging?

Yes, there are. The key trend is that there’s no need to go through a regulatory pathway, to first go through the FDA, and then go through the litigation at the district court level. So, what we’ve seen over and over is an opportunity to identify patents of interest, and then go to court on declaratory judgement actions right away. That’s the way to get to the market sooner and at least get the patent issues resolved—perhaps before investing the millions of dollars required for the regulatory side.

Imron Aly, JD, partner at Schiff Hardin, LLP, discusses key trends emerging in Biologics Price Competition and Innovation Act (BPCIA) litigation. 

Imron Aly, JD: Key Trends in BPCIA Litigation

What are some of the issues at stake in the 

So what that will end up meaning is, 1 of 3 things could happen. One, the Supreme Court could say that [inter partes reviews, IPRs] are not constitutional, and that means that no one can use that way to challenge validity of a patent. The second thing that could happen is the same thing, but only for a prospective, going forward, nature—saying that what’s happened has happened, but going forward, no one can use that system. Third&mdash;what I think most people are predicting would be likely to happen&mdash;is that the Supreme Court would say, they’re constitutional, and perhaps limited in certain ways of executing them, or requiring procedural safeguards for when and how they’re used, but that they’re likely to be constitutional. So those are some of the issues at stake.

Speaking with the The Center for Biosimilars® the day before the Supreme Court of the United States ruled in Oil States Energy Services, LLC, v Greene’s Energy Group, LLC, Imron Aly, JD, partner at Schiff Hardin, LLP, explained the issues at stake in the case.

Imron Aly, JD: The Issues at Stake in Oil States

What is the role of advocacy groups in patent opposition?

The role of an advocacy group or a legal group such as ours is to ensure that patents are only given to truly deserved inventions.

By that, I mean if something is not merited—the science behind it has already been published, has already been known in other literature [or] in the field itself&mdash;then really our job is to make sure that the patent is not granted in that sense because that then blocks competition, which means higher prices, which means research can’t happen. It can mean a number of things.

And so, our role is to make sure that that knowledge stays open and free so that it can actually be used, whether that be by competitors, generics, biosimilars, or whether it’s in terms of research.

Tahir Amin, DipLP, co-founder and director of intellectual property of Initiative for Medicines, Access, and Knowledge, discusses the role that his group plays in patent opposition.

Tahir Amin: The Role of Advocacy Groups in the Patent System

What is a “pay-for-delay” strategy, and what effect does it have on generic drugs or biosimilars reaching patients?

So using the Humira example, Amgen recently tried to come into the marketplace with its own biosimilar, and has now settled with AbbVie rather than go through the whole litigation process. Rumor has it that Amgen won’t get into the market until 2023, whereas it could’ve potentially come into the market now. So that’s a classic example of a settlement where litigation is involved.

Today, since the Supreme Court ruling on “pay-for-delay” settlements, we don’t see as many that are coming through, but there are other types of settlements which are happening [that] we don’t know the terms and conditions of. It might not involve money, but it may involve some other incentives or some other payback in a different way which may not be monetary, but could be other ways; we may give you another market but don’t come into the [United States]—it could be various things.

Ultimately, these deals are actually designed to maintain the maximum profit for the brand holder, the patent holder, and give some kind of exclusivity to whoever they’re settling with, but it doesn’t open the market. It allows the control of the marketplace which unfortunately all falls back on the payer and the public. 

Tahir Amin, DipLP, co-founder and director of intellectual property of Initiative for Medicines, Access, and Knowledge, discusses how settlements can impact patient access to biosimilars.

Tahir Amin: Pay-for-Delay Settlements and Patient Access

Drug makers often argue that developing a drug is so costly that high prices are warranted to recoup their costs and reward innovation. What do you think about that argument?

I think that’s a fair argument, and we know that there are a lot of costs that go into drug development and research. What those exact costs are we don’t exactly know, it’s a bit of a black box, and I think some transparency around that would be helpful so that these debates and these discussions can be more informed. But we don’t believe that all the various patents that are being filed warrant or explain all the costs and the sort of profits that are being made as a result of these strategies that companies are using in order to prevent competition.

I think those are separate issues, and they need to be unpackaged better to have a better policy to help both the payers and the public in order to get fairer pricing; but also to actually better improve what kind of [research and development, R&D] is done, what kind of innovation comes out of the system because at the moment I feel the patent system is an incentive mechanism which is not functioning at its highest possible way.

Tahir Amin, DipLP, co-founder and director of intellectual property of Initiative for Medicines, Access, and Knowledge, a public interest team of attorneys and scientists who ensure that patents do not obstruct access to affordable medicines for patients in the United States and around the world, discusses transparency in drug pricing.

Tahir Amin: Transparency in Drug Pricing

Are patient-assistance programs on the whole good or bad?

Well, we know that many of our community members rely on them to receive their therapy, so they’re very important. I think what is also important with patient-assistance programs is understanding that sometimes they can be abused. Our fear is that when they are abused, or when they’re used by individuals that may not actually need them, so to speak, it could compromise patient-assistance programs in general for the folks that are most vulnerable and need them.

I would point to a white paper that our organization did in collaboration with the University of Michigan [Center for Value-Based Insurance Design]. It looks at precision patient-assistance programs [and] how we can identify those vulnerable patients most at risk from a clinical standpoint and from a financial standpoint and making sure that co-pay assistance programs are available specifically to those individuals so that we can get people on the right treatment quickly.

I think it’s a balance. I think we need to be more responsible about applying co-pay assistance programs to individuals so that we can guarantee that they’ll be around for a longer period of time.

Stephen Marmaras, director of policy and advocacy for the Global Healthy Living Foundation, discusses value and patient co-payment assistance programs.

Stephen Marmaras: Value and Co-Payment Assistance Programs

How do patients feel about the idea of switching to a biosimilar from their existing biologic therapy?

They don’t feel great about it. When I talk to patients and when my colleagues talk to patients within our 50-State Network, which is really a collection of advocates all across the country in all 50 states, they tell us that it causes them anxiety. I think that’s really what informed my earlier point about education being so important here. We have a mountain to climb in terms of the understanding of biosimilars currently with patients.

Oftentimes, the folks that we work with every day, it’s taken them years, if not a decade, to find a biologic therapy that works for them. They’ve tried in some cases, 5 or 6 drugs and they’ve finally found 1—they finally found this oasis where they’ve gotten freedoms back, they’ve gotten their lives back. I think that for many people, these drugs are not [just] drugs, they represent something completely different, they represent their independence, they represent a life before disease.

When you tell a patient “We have this new, cheaper option that’s similar but not the same, it’s likely to produce the same results as the other one,” you put yourself in their shoes. Imagine yourself going through the 10 years of struggle to finally get something that works, and now they’re supposed to roll the dice and take a gamble on a drug that someone else is telling them works the same.

I think we have to answer that question for them. We have to be able to prove in a very succinct way that they should be confident in that switch. But most importantly, we have to be able to show them how they’re going to benefit other than just physically, because they’re the ones that are taking that risk, they’re the ones that are rolling those dice. They’re the ones that are going to be either self-injecting with the drug or sitting in an infusion chair.

What benefit do they get beyond just your promise that it’s going to work the same? What actual savings are they going to feel? Are they going to have similar co-pay assistance programs? We talked about co-pay assistance programs earlier and how important they are for patients to get access. Are they going to have the same sort of general support services, hotlines that they can call if they don’t know how to use their auto-injector or if they have a question about an infusion that they just had.

Patients have begun to rely on not just the drug but kind of everything that goes along with it. So, that’s our concern about biosimilars: we need to be able to show patients that all of that is going to be the same. Not just the result. And then some: you’re also going to be able to feel a benefit in your purse or in your wallet. 

Stephen Marmaras, director of policy and advocacy for the Global Healthy Living Foundation, explains what patients will need to feel comfortable with switching to a biosimilar.

Interviews