What should patients understand about biologic therapies versus conventional disease-modifying anti-rheumatic drugs? 

All of them are intended to reduce this sequence of immune infiltrates and proliferation inside of joints that causes destruction. All of them have a role in doing that. The conventional [disease modifying anti-rheumatic drugs] DMARDs are the older therapies that we used to use. Some of them are excellent. Our baseline, or our base case of therapy, is methotrexate, and when used properly, it can get lots of people into remission. Methotrexate, when used sometimes with another conventional DMARD—or even 2–can get people under good control, so nobody should ever diss those, and in a way, they’re safer. 

And so, we like the conventional DMARDs, but the problem with them is some people have side effects, as they could have side effects to anything. It’s hard to remember always to take the medication. There are some conventional DMARDs you have to take 4, 6 times a day, which is not so easy. Some people have trouble with weekly, and some people don’t take all [of it], they vary it, and so it doesn’t have a chance to be as effective as it could be. Usually in situations where people tend to vary it, they have some fear about it, or they may be having side effects, and it would be much better if they would speak to us, so we can work around them rather than just reducing doses.  

The methotrexate is also very good at reducing the body’s rejection of biologics. So, on occasion, biologics—they’re still foreign proteins–and the body can reject them. Methotrexate limits that rejection, and we see in study after study after study, that when you combine methotrexate and a biologic, even if the methotrexate is at a lower dose, those people do better over time. Biologics are proteins. These are the ones that have to either be injected or infused, but basically, they’re proteins, and they’ve been made to reflect something in the body.

There are some that have been made to be like receptors we normally make, and some of them have been made to be other antibodies targeting a receptor or targeting something in that immune process that is going on. And now, we have targeted synthetic DMARDs, and those basically have the power of a biologic, but they’re a pill. They now target specific pathways inside cells to treat the disease.  

Videos

Vivian Bykerk, MD, associate attending rheumatologist at the Hospital for Special Surgery, associate professor of medicine at Weill Cornell Medical College, provides an overview of what patients should know about biologic therapies versus conventional disease-modifying anti-rheumatic drugs.

Vivian Bykerk, MD: Biologic Therapies versus Conventional Disease-Modifying Anti-Rheumatic Drugs

What do you see as the future for the biosimilar space?

Well, I think a big part of it is we’re hopeful that these therapies become a big opportunity to reduce costs in the healthcare system while getting the intended benefits of these therapies. 

You look at the generic marketplace and biopharmaceuticals in general, and while it’s taken some time, there are significant cost savings to be appreciated from using generic therapies. So, if you apply that to the biosimilar marketplace, and hopefully we’ll see again significant cost-reductions in the acquisition costs in the use of these therapies, and we’ll see benefits in that area too.

Mark Cziraky, PharmD, CLS, describes what he sees as the future of the biosimilars space.

Mark Cziraky, PharmD, CLS: The Future of Biosimilars

So the BBCIC really started based on a survey of The Academy of Managed Care Pharmacy members about these emerging biosimilars that were going to be coming on to the market, and what do we want to do about them as an organization? 

The resounding theme was, “Let’s not let what happened with generics happen with biosimilars.” What happened with generics was over 20 years ago when we first started to see them come on the market there were anecdotal reports of, maybe, safety issues or not scientifically rigorous information that was coming out in the press, and it really influenced people's comfort level for using generic drugs. Utilization now is very common; all of us use a generic drug at some point, even if it’s just an aspirin; but it took a long time to get to that point, largely because of those barriers in people’s comfort zone. 

Even today, there was a physician survey conducted in 2011, which was not that long ago, about generic drugs. And even then, there was a substantial number of physicians who reported discomfort and concerns about safety, and 50% of them had concerns about quality of generic drugs. 

So, fast forward to biosimilars there was a similar survey conducted in 2015 about biosimilars and physician’s: 78% of them were very concerned about the safety and immunogenicity of biosimilars. So, number 1, that opens up a door for education, but that was really, that whole scenario was really the impetus behind the Biologics and Biosimilars Collective Intelligence Consortium—but I’m going to call it the BBCIC from now on—to do something to create rigorous science in place of anecdotal reports for people to base their decisions on.

Whether its patients, payers, or patients, give them an evidence base that otherwise wouldn’t be there. So that was the formation of the BBCIC. That came together with a panel of very smart people [that] put together the business plan and the consortium was put together in 2015. 

Cate Lockhart, PharmD, PhD, describes how the Biologics and Biosimilars Collective Intelligence Consortium (BBCIC) was formed.

Cate Lockhart, PharmD, PhD: Forming the BBCIC

How has your work affected access to and the cost of HIV therapies? 

I think we’ve seen the cost come down significantly, and a lot of that is because of the advocacy, the patient community, and global health organizations putting this issue on the agenda.

I do believe the newer generations of drugs are still farther out of reach, particularly for middle-income countries. For example, a number of least-developing countries are getting included in access programs or licenses, so those countries are getting some of the benefits of the work that’s being done; however, a number of middle-income countries are being left out since they’re emerging markets.

So, those countries are facing a big crisis in terms of accessing these drugs at affordable prices. I think that’s where a lot of the work has to be concentrated now, because there’s been a tradeoff where pharmaceutical companies have said, “Well, we’ll give to the least-developing countries but keep the bigger markets to ourselves.” So, the prices are still around $5000 to $7000, and there’s more poor people living in middle-income countries than almost anywhere else. That’s where the crisis really lies and if we don’t solve that problem than we’re going to be facing another HIV crisis, as we did in the early days.   

Tahir Amin, DipLP, co-founder and director of intellectual property of Initiative for Medicines, Access, and Knowledge, discusses how his organization has helped bring down drug costs.

Tahir Amin: Bringing Down the Cost of Drugs 

How did you decide to focus on HIV drugs for your work in patent opposition? 

At the time, around 2000, there was this massive uproar by basically people in the developing world who didn’t have access to affordable HIV drugs. I think the prices were around $2000 to $10,000. Then there was a case brought by 40 pharmaceutical companies against the South African government at the time, and out of that grew this access to medicine movement.

At the time, this was basically trying to get cheaper, affordable HIV drugs to low-income people in developing countries. In India, at the time, it was bringing in its new patent law in 2005 and everyone was concerned. Doctors Without Borders was concerned, and called India the “pharmacy of the poor” because it was supplying so much of the HIV medicine, and they were concerned this pipeline would dry up due to patents being granted. 

So, we focused on HIV largely because of that movement, and even today, despite all the great work that’s been done, we’re seeing it’s still a problem. I think recently there was an article saying the number of people getting HIV medicines in the [United States] is not as high as it should be. There’s actually going to be a crisis in the middle-income countries in 2020, and a number of people won’t be able to get HIV treatment. So, there’s still so much more to do and the HIV issue is still central to our work despite almost 10 years of the work we started back then. 

Tahir Amin, DipLP, co-founder and director of intellectual property of Initiative for Medicines, Access, and Knowledge, discusses the role of patent opposition in giving patients access to high-cost drugs. 

Tahir Amin: Patent Opposition and Patient Access to High-Cost Drugs

What are some of the cases you’re working on now? 

So one of the major cases we’re working on is Sofosbuvir, branded as Sovaldi. It’s a hepatitis C drug, and currently we filed 10 IPRs last year in the United States [Patent Trial and Appeal Board, PTAB]. Currently, we’re waiting to hear whether those will be instituted, and by instituted, I mean whether the PTAB will take those cases on and will go into trial. 

We have a number of cases going on in India involving hepatitis C drugs, and in China we already had some successful decisions. 

The importance of these cases is to show that a lot of people are still not getting these new, direct-acting anti-viral hepatitis C drugs, and we feel that our work is to try and create an opportunity for people lacking access to get them. 

Also, in the United States, a lot of people living with hepatitis C are not getting the treatment that they need, and I hope the cases we have brought will leverage some opportunities to try and get these drugs at more affordable prices, because only 1% of the number of Americans that need the drug are getting it at the moment. 

Tahir Amin, DipLP, co-founder and director of intellectual property of Initiative for Medicines, Access, and Knowledge, discusses his organization's ongoing work in challenging drug patents. 

Tahir Amin: Ongoing Work in Challenging Drug Patents

What are some new directions in treating inflammatory diseases that you’re particularly excited about? 

So, the first, I guess, and it’s not that new, is early diagnosis. It’s a way to classify the disease sooner than later, having a blood test to be able to do so in a number of people, though not all. Also, part of it is having people understand that the expectation is to get people into remission in the first year, and then, keep them there, as sort of new standards and new guidelines. Another part of it is the translational side of it. There’s a huge effort to now try and understand how the tissue in the rheumatoid joint is functioning in terms of cell-cell interactions, and sending things in and out of the blood to get a new understanding of how the tissue functions to perpetuate the disease and even start the disease. We don’t think it starts in the joint. We think it starts in the mucosa and something travels to the joint, but we don’t know why. And then a whole interaction of cells comes, and they have a party, basically, and they start to work with each other to build what is more like a benign tumor in the joint, and that, in and of itself, is very destructive.  

Vivian Bykerk, MD, associate attending rheumatologist at HSS, associate professor of medicine at Weill Cornell Medical College discusses new treatments in inflammatory disease.

Vivian Bykerk, MD: New Treatments in Inflammatory Disease

How does the biosimilar market compare to that of generics?

Certainly, with the regulatory pathway, to me, that’s where it diverges. Beyond that, I don’t see it as really being divergent. If you think about biosimilars— if they are approved as a biosimilar– that means they are significantly similar. It’s not identical, you know, because it’s a biologic, but it needs to be substantially similar and [have] no clinical difference. 

In a sense, in spite of the regulatory process, there’s no evidence of any clinically meaningful difference. In that sense, the divergence really is post-regulatory, in my opinion, where it’s a matter of education among prescribers, patients, [and] payers, but then in the United States that’s not really the hurdle for utilization. 

So, I don’t know that this necessarily diverges from the generics scenario other than it is certainly a scenario that we did not fully appreciate would come to pass in that, the reason for slow uptake in the United States is not wholly because of concerns about safety and effectiveness. It’s more tactical on the part of pharmaceutical companies— these are business decisions, this is a business– and that’s perfectly fine. But, the effect is creating a marketplace where even though we now have 11 approved [biosimilar] products in the US, only 3 are currently on the market. 

That’s a place where it diverges from generics in a way, although, we did see similar problems with generics [such as] slow uptake of generics back in the day because of the uncertainty. 

Cate Lockhart, PharmD, PhD, discusses the similarities and differences in the biosimilar and generic markets. 

Cate Lockhart, PharmD, PhD: Biosimilar vs Generic Markets

What role do you see biosimilars playing in increasing access to care?

Biosimliars have the potential to greatly increase access to care. Biologic agents in general have revolutionized the management of many, many rheumatic diseases, starting with infliximab in 1999, which completely changed the natural history of rheumatoid arthritis from what it was prior to the availability of [tumor necrosis factor] TNF inhibitors. Now, of course, we have a whole array of biologics that we can use. So, they’re fantastic drugs as a group, but they’re fantastically expensive— $50,000 a year and upward. And it’s going to bankrupt the system to say nothing of patients who potentially don’t have insurance access to these medications. So, the availability of biosimilars, if they are as efficacious and safe, and if– the big if– the price is low enough, there’s real potential to improve access. The problem has been that the pricing has only been 15% lower than the original drugs, which is nowhere near as low as we originally hoped, and there’s a whole variety of factors that go into that, but it’s something that we need to work on, particularly in this country. In Europe, the price differential is far greater.

Anne Bass, MD, rheumatologist at the Hospital for Special Surgery and professor of clinical medicine at Weill Cornell Medicine, discusses the potential for biosimilars to increase access to care.

Anne Bass, MD: Increasing Access to Care

Will the BBCIC’s work help with patient acceptance of biosimilars?

I think patients overall are much more sophisticated than people often give them credit for, you know, it’s people like me, people like you. So, I think not all of the patients are going to grasp maybe the nuances of what may come out of the research I’m doing with the BBCIC. But also, some of that comes down to how we communicate it. We can certainly put together a story that is appropriate for or is going to be meaningful for a patient or a patient group, or a patient advocacy organization for example, and we are engaging with patient organizations to help inform our research questions which is really helpful, so we’re answering the right questions for them to the extent possible within our constraints.    

I think it’s both educating and providing evidence for physicians to make their decisions, as well as for patients, because the patient has a role in their healthcare obviously. Now more than ever patients are being a lot more in charge of their own healthcare. So, I don’t think we can necessarily split those or silo those. How we communicate our information and our science may be a little bit different depending on the audience, but I think its beneficial for everybody to understand their treatment and their treatment options. 

Cate Lockhart, PharmD, PhD, discusses whether her work with the BBCIC will help encourage patient acceptance of biosimilars. 

Interviews