So I think what’s very important to notice is that biosimilars are used everywhere, in every country. And I think this is important; we’ve had 28 countries until now, and I think it's important to see they are used by every healthcare system. 

The nuance in there is that they are used in a variable fashion. So between countries you see a massive difference, and within countries you also see massive differences between the different biosimilars available.

Videos

Julie Maréchal-Jamil, director of biosimilars policy and science at Medicines for Europe, describes the state of the EU biosimilars market.

Julie Maréchal-Jamil: The Biosimilars Market in Europe

There are a lot of concerns [among] my colleagues treating patients with biosimilar rituximab, and so we decided to do a study in [diffuse large B-cell] lymphoma (DLBCL) because, in this population group, the concerns are very high because this is a curative therapy. We got the data from follicular lymphoma in the pivotal study with Sandoz’s biosimilar rituximab, but we didn't have any data in DLBCL, so we decided to do this study to get data in this population and to make sure that biosimilars are as effective [as] the originals.

Manfred Welslau, MD, Onkologie Aschaffenburg, Germany, discusses the rationale for gathering real-world evidence on biosimilar rituximab. 
 

Manfred Welslau, MD: The Importance of Real-World Data for Biosimilars

Other areas which are kind of coming and delving into more discussion in regards to education and other resources is, of course, what will happen for implementation in the near future, and also pharmacovigilance: How are we tracking this? Are we doing a good job of tracking this? Who's running that ship as well?

The last thing, which is still emerging and has not been had guidance yet, is interchangeability.* We're expecting the draft guidance document, which is actually brought back, to be released here shortly, hopefully in May, and that will provide us with more information about how we can actually switch these biosimilars before we can switch these with therapeutic interchange at many hospitals, clinic sites across the board.

But what happens when it goes to a specialty pharmacy outside of your network? Will they be able to switch a pegfilgrastim for self-injection? Will they be able to actually self-inject a short-acting growth factor without contacting the doctor?

We have seen a lot of state laws being passed, and there’s going to be state regulation with state boards of pharmacy, but also the federal law and state law may have to have further discussions as well.

So I think those areas, and hopefully they’re not too much, provide some opportunities for further discussion, and also opportunities for patients who are trying to get these drugs at a lower cost and also improve access as well.

*As of the date of filming. To read about the FDA’s finalized guidance on interchangeability, 

Ali McBride, PharmD, MS, BCPS, clinical coordinator of hematology/oncology at the University of Arizona Cancer Center, discusses areas where pharmacists still have questions about biosimilars and their implementation.

Ali McBride, PharmD, MS, BCPS: Pharmacists' Concerns About Biosimilar Implementation

It’s hard to say whether the number of settlements in the biosimilars arena indicate a shift away from lengthy BPCIA litigation. Many of those settlements have been entered into after litigation that some would probably say was lengthy.

And I think it’s a little too early to know how this will shake out. There’s a couple factors at play: One is that the courts and the [Federal Trade Commission, FTC] and Congress have started to pay more attention to settlements in the biosimilar space. We could see activity from anyone of those bodies or from the plaintiff’s bar that might discourage settlements going forward.

We could also see changes in the ways these cases are managed by the courts, or in the risks that both biosimilars manufacturers and the brands face that might impact whether settlements take place. Because of course, generally speaking, a settlement happens when both parties have risks.

Elaine Blais, JD, partner at Goodwin and head of the litigation department in Goodwin’s Boston office, discusses whether a recent spate of patent settlements related to biosimilars reflects a shift away from lengthy Biologics Price Competition and Innovation Act (BPCIA) litigation. 

Elaine Blais, JD: Trends in Patent Settlements

So patients have access to our helpline. They are able to either email us or call us if they do have a problem once switched. We’ve also, with our local support group, they have helplines that they can call. There’s lots of mechanisms to feed back any queries and to support patients who’ve switched.

Kalveer Flora, MPharm, London North West University Healthcare National Health Service Trust, discusses patient support options for those who switch to biosimilar adalimumab in the United Kingdom.

Kalveer Flora, MPharm: Patient Support During Switching

Well again that's yet to be seen. Of course we do have a biosimilar rituximab as you allude to. It’s now approved in the United States, and it’s actually been in Europe for a longer period of time, so we have some experience there, and in fact as last year's [American Society of Clinical Oncology, ASCO] meeting last June, a European group presented data on the early utilization of rituximab in patients with lymphoma in Europe. 

What was interesting there, and I think we may see the same thing happen here in the United States, is the utilization of the biosimilar rituximab was more favorable in patients with less curable forms of lymphoma. In other words, the oncologist was willing to use these new agents in a situation where the goal wasn't necessarily long-term survival or cure. They reserved the originator, Rituxan, for use in patients with, for instance, diffuse large B-cell lymphoma where the goal of treatment is usually cure. 

There’s some discrimination in the use of that, which is perhaps understandable because this is not just supportive care. This is the mainstay of treatment for these patients, and if you're treating for curative intent, do you really want to take any chances if you're not quite sure, or if you haven't used the drug before?  

So you’re more likely to use it in solid tumors in patients with metastatic disease perhaps or lymphoma with the low-grade lymphomas where your goal is extending life but not so much the likelihood of curability. 

That’s data from Europe, but my guess is we're going to see a similar kind of gradual intake and then over time broad utilization across the subtypes of lymphoma.

Gary Lyman, MD, MPH, of the Fred Hutchinson Cancer Research Center and Seattle Cancer Care Alliance, discusses how biosimilar rituximab may be used in cancer care.

Gary Lyman, MD, MPH: Using Biosimilar Rituximab

The Supreme Court’s January 2019 decision in 

 is an important decision for biologics manufacturers and biosimilar companies. In that case, which was argued by our partner [William Jay, JD], the Supreme Court held that an inventor's sale of an invention to a third party could trigger the statutory on-sale bar even where the third party was obligated to keep the invention confidential.

This case has important implications for biosimilar manufacturers in that it is a warning that they need to be very careful about the types of contracts they enter into prior to applying for a patent. And it is an opportunity for biosimilar manufacturers in that it opens the door for potential on-sale defense invalidity argument, and biosimilar manufacturers should be careful to investigate and take appropriate discovery to determine whether such a defense is viable in any given case.

Elaine Blais, JD, partner at Goodwin and head of the litigation department in Goodwin’s Boston office, discusses the Supreme Court’s January 2019 decision in Helsinn v Teva.

Elaine Blais, JD: Helsinn v Teva and Its Implications for Biosimilar Developers 

That's very interesting question, because the prescribers are still not aware of the rigorous pathway—there’s something called the totality of the evidence that’s undergone in terms of evaluating the molecule. Many prescribers even now think that biosimilars and generics are the same. There’s a significant difference and a significant cost difference in developing a biosimilar, so there are a lot of misconceptions prevailing among my colleagues as well as many prescribers. As a chairman of the biosimilars committee at the [Community Oncology Alliance, COA], we’re trying to help address the knowledge gap and the needs assessment in the biosimilars market.

Kashyap Patel, MD, discusses the prevailing misconceptions about biosimilars among oncologists. 

Kashyap Patel, MD: Misconceptions About Biosimilars

I don’t know if you know that in the [United Kingdom, UK], biosimilar rituximab has taken the entire market. There’s no biosimilar subcutaneous, but the biosimilar intravenous basically has had a massive impact with respect to cost. The biosimilar that’s used in the UK was over 40% cheaper than the MabThera. From a healthcare system that buys a lot of drug, that’s a big, big impact. So from an intravenous point of view, we’re using the biosimilar. I don’t have a choice; that’s what we’re doing. But of course there's only 1 subcutaneous.

Certainly in the maintenance setting, the hidden costs of somebody being in a chair all afternoon versus the subcutaneous are massive. Even within the [National Health Service, NHS], that’s recognized. So subcutaneous within a maintenance setting is allowed. I think in maintenance, you need to give the subcutaneous. You could argue whether intravenous when you’re giving somebody intravenous chemotherapy is cost effective or not, and maybe it is because the patient is in the chair anyway. So that’s perhaps where you could argue for a biosimilar intravenous, but certainly maintenance, I don’t think there’s any role for an intravenous formulation over a subcutaneous one.

Simon Rule, MD, Plymouth University Medical School, discusses the role of biosimilar rituximab in the era of subcutaneous reference rituximab in oncology. 

Simon Rule, MD: Subcutaneous Rituximab Versus an Intravenous Biosimilar

At the policy level, among professional organizations like [the National Comprehensive Cancer Network, NCCN], again, I think there’s this hesitancy. This need to be educated. There, I think the biggest issue is they want to see the data. They want to see the evidence, and since these drugs are being approved by the FDA, sometimes that evidence is put in the public domain; it’s put on the web. If there's an Oncology Drug Advisory Committee meeting, all that's in transparent and available.

But the more recent biosimilars have been approved without that public disclosure. There, it's really critical that industry, that companies publish their data, their preclinical data and their clinical data, in the peer-reviewed literature.

We had one example recently, and that complicated our NCCN guideline update for the hemopoietic growth factors, where we neither had the public display of the evidence that the FDA reviewed nor any peer-reviewed publications. So as a guideline panel, we could not really recommend the use of that agent.

Eventually, the company forwarded that information to us directly, but my point is, FDA approval is just the first step, and equally important is that the evidence that the FDA reviewed for approval these agents has to be made available to the medical community, to the professional community, and to professional organizations like NCCN if they're going to be expected to endorse and recommend the use of these agents.

Gary Lyman, MD, MPH, of the Fred Hutchinson Cancer Research Center and Seattle Cancer Care Alliance, discusses policy challenges with biosimilars. 

Interviews