In my own hospital, we’ve been using subcutaneous rituximab for quite a few years now. We did the early studies, and it’s made a massive difference, not just with respect to your day unit, your nursing resource, the chair time, but also with respect to the patients. 

So, we did a time-and-motion study, which was published some time ago, comparing intravenous with subcutaneous. We actually timed patients from the minute they walked in the hospital door to the time they walked out. 

Whilst on the face of it, an [intravenous] infusion is 90 minutes, the patient’s actually in the hospital for nearly 4 horus by the time they’re in and out. With a subcutaneous, you literally can give and go. You don’t have to give any prophylaxis. So the patient has the injection, it takes about 5 minutes, and they can leave. So that’s a big, big difference. It’s a fixed syringe, so you don’t have to preorder it. 

You can give it outside the hospital setting, of course, and the big difference we saw is maybe not so much for the patient but for the relative; because these patients are often elderly, they’ve got their son or daughter taking off work to go to the hospital. If it only takes half an hour rather than all afternoon, then that’s a big, big impact. I think that’s often not looked at particularly. We just focus on how long the patient’s in the chair getting the drug for, but actually, it’s a big impact.

Videos

Simon Rule, MD, Plymouth University Medical School, discusses how subcutaneous rituximab has impacted clinical practice. 

Simon Rule, MD: The Impact of Subcutaneous Rituximab on Clinical Practice

I think, specific hurdles, and I think we hear this a lot: “Are the biosimilars safe? Are they effective? Are there any side effects?” Having gone through the switches, at each stage, we collected data to show that the biosimilars were just as safe, just as efficacious, worked just as well as the originators. 

This mound of evidence helped build confidence at each transition. So our clinicians, our nurses, our pharmacists, our physiotherapists, all of our multidisciplinary team could see that, because we had this wealth of experience, at each stage, they became more confident. So now our consultants wouldn’t even think about having a problem with switching, whereas, in the beginning, we had problems with, “Oh, do they work? What happens if a patient feels that their condition has deteriorated once on it?” 

I think, having gone through the process 4 times now, this has helped to build confidence at each level, and now it’s more of a routine thing rather than a new thing.

Kalveer Flora, MPharm, London North West University Healthcare National Health Service (NHS) Trust, discusses how the NHS has overcome hurdles related to switching to biosimilars. 

Kalveer Flora, MPharm: Overcoming Hurdles in Switching to Biosimilars

Real-world data are something that are needed, and actually that is one of the huge problems we have. For companies selling biosimilars, real-world data are after-sales service. It’s very difficult to get funding for that. 

We are at the moment planning a study, a real-world study on cardiac safety. We’re trying to predict cardiac safety with early endpoints by drawing blood after 2 cycles of the biosimilar—of antibody&mdash;trying to measure in the blood biomarkers that may predict cardiac failure in patients. 

This is a classical real-world study, and this is very important because cardiac safety, the cardiac signals in trastuzumab trials, have been decreasing over the years, not because trastuzumab is less cardiotoxic, but because people are more aware of cardiotoxicity, and of course the inclusion/exclusion criteria have been developed and are more strict. So we may ask ourselves, is this really real-world that we’re seeing? 

This is why we believe doing a real-world study—and actually, we found a sponsor for that study&mdash;it’s very important to include all patients who are, in the real world, candidates for trastuzumab in a safety study, and not only from a clinical registration trial. Of course, inclusion/exclusion criteria are designed so you’re safe for ethical reasons.

Hans-Christian Kolberg, MD, head of the department of obstetrics and gynecology, breast cancer center, and gynecologic cancer center at Marienhospital Bottrop, Germany, discusses the role of real-world evidence for biosimilar trastuzumab.

Hans-Christian Kolberg, MD: Real-World Evidence and Biosimilar Trastuzumab

In Denmark, we believe in science, and as I said, Humira has been wiped off the Danish hospital shelves.

I was attending a conference of Medicines for Europe about a month ago, and people were asking what is the biggest obstacle—all the participants were being asked what is the biggest obstacle to introducing biosimilars into, I think it was the European market. I didn't say this, but funnily enough the 2 answers people gave were AbbVie and Roche. That was quite significant; I mean, I think that people might have been thinking along those lines, but expressing it so freely and so clearly at an international conference, where, you know, 10 minutes after it was all over the social media.

I don't think that is going to be a challenge in Denmark. It might be a challenge in other countries in Europe where you have incentive systems that do not always make it better to use biosimilars; I mean, some doctors would continue to prescribe the branded product because they make more money on that, and maybe the companies can, you know, the originators can do their magic and create patent problems or whatever. 

Fortunately, so far, that hasn’t seemed to be the case in Denmark. We’ve had discussions with patient organizations, of course, which is completely legitimate. Sometimes, we have been able to detect that behind the patient's organizations, there was a helping hand, if you will, from some of the big companies who had a lot of financial interest at stake, and were quite willing to supply patient organizations with critical questions like “Why don't we have more clinical tests? Do we really have enough information? Shouldn't we just wait and see?” and stuff like that, which was clearly in opposition to the rapid introduction of biosimilars.

But as I said, it didn't really seem to have very much effect, and I don't think it will in the future. Biosimilars in Denmark are a huge success, and there's no reason to see why that should change.

Peter Jørgensen, director of the Industrial Association for Generic and Biosimilar Medicines, Denmark, addresses whether challenges lie ahead for biosimilars in Denmark. 

Peter Jørgensen: Challenges for Biosimilars in Denmark

We need to make really substantial progress on waiving of bridging studies where the comparator products used are just another version of the local reference product. 

So how are we going to do that? I think we have of course the excellent 

 of Christopher J. Webster and Gillian R. Woollett, DPhil, which has laid the scientific basis for this reflection that eventually we have only 1 comparator product on the market, which should be the basis for the biosimilar development. That’s one thing.

But how do we get this forward? Because the science is there, because these products are based on the same clinical data package, even versions which are on the market around the world. I think what we are probably going to do is of course we’ve had some interaction with some agencies. We’ll further talk about it at different conferences to get the ball rolling, keep the momentum. 

It should be a key priority for the [IPRP, the International Pharmaceutical Regulators Program], there is a biosimilar working party, and the IPRP (it was formerly IPRF); this is for me the largest forum for the moment where biosimilars are discussed, and it should be a key priority to look into that. 

Suzette Kox, MPharm, secretary general of the International Generic and Biosimilar Medicines Association (IGBA), discusses the need to waive bridging studies in biosimilar development.

Suzette Kox, MPharm: Bridging Studies and Biosimilars 

Again, we're very early. The first biosimilar [granulocyte colony-stimulating factor, G-CSF] was approved just in recent years. We now have another biosimilar that was approved as an originator, tbo-filgrastim, and 2 true biosimilars in the [United States], the forms of filgrastim, and now just over the last few months approval of the long-acting filgrastim, pegfilgrastim, which has been available in Europe but now is also available in the [United States].

But this is brand new data. In fact, in many institutions, it isn’t even available yet as the drug gets distributed. So the only data that we have is from the filgrastim originator versus the filgrastim-sndz, which was approved a couple of years ago, and the data there suggest there's been rapid uptake of the biosimilar filgrastim; at least half, maybe two-thirds of the utilization of G-CSF in the United States has switched from the original drug to the biosimilar.

The impact on cost is more challenging, and again very preliminary data. But as I alluded to, perhaps showing around a 10% the 12% decrease in price over the first year or 2 of the use of the biosimilars. 

One will expect (again, in Europe, they’ve seen this) with time and with more and more competition, more and more biosimilars, there will be further reductions in pricing, perhaps to the extent of a 20% to 30% decrease.

Gary Lyman, MD, MPH, of the Fred Hutchinson Cancer Research Center and Seattle Cancer Care Alliance, discusses how biosimilar granulocyte colony-stimulating factor (G-CSF) therapies have impacted cancer care.

Gary Lyman, MD, MPH: Biosimilar G-CSFs and the Cost of Care

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.

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. 

Interviews