So the first biosimilar, in fact the only biosimilar in the United States, was approved nearly 2 years ago* and it was based, as I indicated, largely on the preclinical work and pharmacokinetic, pharmacodynamic data and healthy volunteers.

They did run 2 large phase 3 trials, but in patients with chronic kidney disease, not in cancer patients. So in actual fact, the only data on cancer patients with the epoetin alfa biosimilar is observational, not randomized controlled trial data.

Now, it turns out that there is this drug is also available in Europe, known as epoetin zeta. It's essentially the same molecule that’s been approved in Europe. There, they have done large phase 3 trials in patients with cancer showing noninferiority to the originator epoetin alfa. No safety concerns, no immunogenicity concerns.  

So the FDA was willing to accept the data from the same drug in Europe plus demonstration of safety and efficacy in advanced kidney failure patients in the United States and say “this should work the same for supporting patients with chemotherapy-induced anemia.”

That indication is not nearly as frequent as it used to be. A lot of concern was raised a few years ago, so the use of these agents as opposed to transfusions has fallen off in the United States, but nonetheless, to have competitive biosimilar versions to lower the prices of these drugs hopefully will work to the advantage of of patients in the overall healthcare system.

Videos

Gary Lyman, MD, MPH, of the Fred Hutchinson Cancer Research Center and Seattle Cancer Care Alliance, discusses the role of the first FDA-approved biosimilar epoetin alfa in cancer care.

Gary Lyman, MD, MPH: Biosimilar Epoetin Alfa in Cancer Care

The biggest challenge with biosimilars now is that they're new. The regulatory process to get a biosimilar approved by the FDA is very different than the originator product, and so I think physicians have to get more comfortable with understanding how it was done.

The big difference is that they don't require a lot of large-scale phase 3 trials on the clinical level. It's really about showing that the molecule is is highly similar to the originator molecule, which of course, being biologicals, every batch is a little different anyway. Even in the originator molecule you see the same thing with biosimilars.

So the FDA concentrates on a host of technical factors to show that they're very similar and less on the clinical side. We might not have a clinical trial with a biosimilar for every single indication that the originator has, but the label will show the same indications. In fact, the labels come from the original, largely, so I think oncologists have to get comfortable with the idea that these drugs are really can be substituted in the new patient for the originator drug at a much lower cost.

That's the real value of a biosimilar: they cost less to be developed, and therefore, on the market, they are one of many solutions to reducing the total cost of cancer care, which we need to do; it's just unsustainable.

So I think as more drugs come out, as there's more education about what a biosimilar really is and how they can be used in your clinic effectively, we’ll see oncologists will become much more comfortable with it.

Lee Schwartzberg, MD, FACP, medical director and senior partner at The West Clinic, explains what he sees as the main challenges with incorporating biosimilars in the cancer clinic.

Lee Schwartzberg, MD, FACP: Challenges With Incorporating Biosimilars in the Clinic

I think that's the very large question, of course, but maybe let me sum up. According to our US colleagues, when I look at the United States, of course the biggest, key challenge is definitely the famous “patent thickets” linked with all the patent litigation. And the misinformation [and] scaremongering. I think scaremongering is very dangerous. When patients get information, it’s difficult to let go.

Those are very important things; even in the European Union where we have been dealing with biosimilars since 2006, we still need to continue to educate and inform. I think that’s crucial and we cannot give up on that. It has to be permanent access to information and new ways of explaining, so that’s very important.

Also, according to our US colleagues, we really need strong incentives for the United States, and incentives which are across the different stakeholder groups, and then uptake measures in order that somehow, one day, the biosimilar market takes off in the United States.

Of course, it is very complex, but maybe these are the key elements there; those who are familiar with the US environment know what I’m referring to.

With regard to the European Union, as you well know, I think we have a lot of experience. Maybe we have today with the EU approved biosimilars maybe 800 million patient days or even 900 million patient days experience. So biosimilars are accepted. They are accepted as being safe and efficacious alternative treatments.

We also have very good experience with switching. It is regarded as safe. The medical societies and medical communities are endorsing that publicly more and more.

Nevertheless, again, education has to continue. It’s never finished. There are new molecules coming out, new biosimilars, there are new treatment areas where biosimilars are first. When the first cancer biosimilar monoclonals were approved, we had to start again in those communities. It’s a never-ending approach; it’s very important.

Certainly now the key challenge for the European Union is that [while] biosimilars are broadly accepted, we need to now strike a balance between, I would say, short-term cost savings and then long-term sustainability for this industry.

It is of course very complex, but that’s what we have to look at because, I think, that’s also valid for the United States. We have to have policies in place which assure long-term sustainability for this industry. Otherwise, they will not further invest into biosimilar development.

Suzette Kox, MPharm, Secretary General of the International Generic and Biosimilar Medicines Association (IGBA), discusses challenges faced jointly by the US and EU biosimilars markets.

Suzette Kox, MPharm: Shared Biosimilar Challenges in the United States and Europe

In the EU, we've been on the educational journey for now 13 years, and if we look at the situation, we have a pretty rich base of documentation, communication materials. What I think has been a game-changer in the educational aspect is when the government institutions, authorities have stepped in and realized that they needed to tailor information.

We started with a general document in 2013 which was developed in a multistakeholder fashion. Then we also collectively looked at having dedicated patient materials and the healthcare professional [European Medicines Agency, EMA] document last year.  

All of that together, we are answering the availability of documentation, the legitimacy of the source, which is extremely important. We’ve also tackled the suitability of the language used, the level for the user.

What remains to be done, you may have seen in the last days, is maybe there's still a different level of understanding between the European levels, be it organizations like patient groups, industrial groups, and maybe what happens at the national level. Another barrier is the language, not in terms of suitability, but in terms of simply English, Spanish, Romanian, or other languages, which actually can be a very important hurdle for local acceptance and growth in confidence.

So in terms of education, I think there's still a lot going on, but it will be more in the dissemination and into empowering local actors.

Julie Maréchal-Jamil, director of biosimilars policy and science at Medicines for Europe, describes current educational needs around biosimilars.

Julie Maréchal-Jamil: Biosimilar Education in Europe

Biosimilars are approved by the FDA based on a different mechanism than the original products. So the original biologics, some of which go back 20 years, were approved as an originator, an innovator drug. They had to provide not only the preclinical data but several randomized controlled trials demonstrating efficacy and safety.

Obviously that's an extremely costly process, and to facilitate the development of biosimilars, a more expedited process was put in place by the FDA a few years ago which put much more emphasis on the molecular characteristics, structure, and its biologic behavior in the patient: pharmacokinetics, pharmacodynamics, whether there are antibodies formed, immunogenicity, all these things to demonstrate that it’s very similar, highly similar to the original product, but without the necessity of going through the multimillion-dollar, large, randomized phase 3 trials.

Some some of the biosimilars have done that anyway, but the idea here is to reduce the cost of development so that that cost reduction could be passed on in terms of lower pricing and greater competition in the marketplace. So it's really a focus on the preclinical work and the safety in patients, and the assumption that if it's virtually the same molecule, same mechanism of action, doesn't have any safety concerns, it will function essentially the same as the original biologic product.

Gary Lyman, MD, MPH, of the Fred Hutchinson Cancer Research Center and Seattle Cancer Care Alliance, describes the biosimilar approval pathway in the United States.

Gary Lyman, MD, MPH: The Biosimilar Approval Pathway

So we’ve already seen 2 biosimilars come to market. We have Udenyca and Fulphila, both drugs are FDA approved for the current indication for pegfilgrastim this setting. So we've seen the actual market start to develop. A lot of discussion has been utilized. We’ve seen some quick implementation for Fulphila and also Udenyca; many sites across the country are transitioning towards that, but also what’s going to actually be distinguished in this discussion is we’re also seeing payers put those biosimilars as a first-line suggestion for therapies in terms of not using the brand-name product.

As you move forward with these pieces, which payers will define what type of biosimilar they use or what maybe their step edits will be for treatment, then it will actually be up to the site or institution to put them in stock.

So if we actually see the emergence of 4, 5, 6 biosimilar pegfilgrastims in the market shortly, the problem will be, will each payer define what type of biosimilar they’ll use? That's going to be very tough for us or any institution any of our [Association of Community Cancer Center, ACCC] members out there, any of our cancer centers. They'll have to stock each one and figure out what type of biosimilar to use per patient.

What makes it worse, or even more confounding, is the amount of time that needs to be noted for that. For the technician, the buyer in this case, but also if you have maybe 5 different companies making biosimilars, and then you have 10 biosimilar lines—a rituximab, and Avastin, a Herceptin, you may have your short-acting growth factor and long-acting growth factor&mdash;you start to name these therapies as they evolve, if payers don't actually have a more concise attitude or discussion point for these biosimilars, it will make it very tough to address what pegfilgrastim you have, or if you need to carry many other pieces of that as well.

Ali McBride, PharmD, MS, BCPS, clinical coordinator of hematology/oncology at the University of Arizona Cancer Center, discusses experience with biosimilar pegfilgrastim so far.

Ali McBride, PharmD, MS, BCPS: The Impact of Biosimilar Pegfilgrastim

Biosimilars are a way of life now; they’ve come on strong and we started with the supportive care drugs, particularly the growth factors. Physicians have to get comfortable that a biosimilar will deliver the same value, the same kind of response, that any other treatment, the originator drug, did. 

 to show that a biosimilar filgrastim gave the exact same results as the originator filgrastim, so that gives comfort to oncologists that they can use a lower-price alternative that has all of the efficacy and all of the safety of the originator product.

Lee Schwartzberg, MD, FACP, medical director and senior partner at The West Clinic, discusses his research that showed that the incidence of febrile neutropenia was similar between patients who received reference filgrastim versus those who received a biosimilar. 

Lee Schwartzberg, MD, FACP: Biosimilars and Neutropenia

It’s very straightforward: they can continue that policy. First, it is a scientific approach to allocate the same INN, international nonproprietary name, to the biosimilar and the reference product. That’s a scientific matter, that’s the first thing.

Secondly, we heard in the biosimilars conference today* again that there is a publication by European regulators and academics which has demonstrated that the identification of biologics—I think they looked into 10 different classes of biologics for which biosimilars exist&mdash;identification based on the INN and brand name is assured by 96.7%. So, it really works. And this will continue to work in the future.

*During the Medicines for Europe 17th Biosimilar Medicines 

Suzette Kox, MPharm, Secretary General of the International Generic and Biosimilar Medicines Association (IGBA), discusses the European experience with using nonproprietary names for biosimilar pharmacovigilance. 

Suzette Kox, MPharm: Pharmacovigilance and Nonproprietary Names for Biosimilars

How do you address patient concerns about switching to biosimilar insulin?

The biosimilar insulin is equally effective and safe. As are the other insulins. For instance, if you used in the past insulin from company A, and you were switched to B because of other things, no one complained about it. Now we have the biosimilar and everyone says "switching for insulin?" It’s not necessary to be worried about it. It's the same. You have no immunogenicity, not with insulin. Insulin is a safe drug.

It's not the insulin, it’s also the device that plays a role. Each insulin company has its own device. So some people are reluctant to switch, because then they have to use another pen, another device. That’s why it’s important that the diabetic nurse educates the patient about the switch, and that the doctor has enough time to explain why he’s switching [the patient's drug].

For the patient, it’s difficult, because price is for her or him less important,* because as a patient, in diabetes, you are chronically ill. You use one drug for many years, so if you are satisfied with one insulin and one pen, why should you switch?

“What’s in it for me,” the patient asks, and that’s difficult to answer. It’s not only the price, but maybe through innovation we develop better devices, and we assure the patient that no shortage will appear when they have the biosimilar.

*In the Netherlands, patients are subject to much lower out-of-pocket costs for prescription drugs, including insulin, than in the United States. 

Anton Franken, MD, PhD, endocrinologist, discusses how to communicate with patients who are going to be switched to biosimilar insulin.

Anton Franken, MD, PhD: Counseling Patients About a Switch to Biosimilar Insulin

How might the new trade deal among the United States, Mexico, and Canada impact biosimilar availability?

Certainly for Mexico and Canada, one of the particular clauses that has been inserted in the agreement is the requirement of data exclusivity or clinical trial data, and Mexico only used to have 5 years and now they have required a minimum of 10 years. So in at least in Mexico they’re going to have a delay before seeing biosimilars, and in Canada it used to be 7 years and they’re going to have to increase it to a minimum of 10 years.

What’s also important is the United States has 12 years already, so it’s already in that minimum period of 10 years, but there’s a lot of conversation, various bills that are in the pipeline in the United Sates to try and reduce that 12 years to 7 years, which is what President Obama tried to do in the outset.

Any chance of rolling back to 7 years that is going to be less given that this trade agreement has been signed, and I think this is one of the strategic moves that a branded pharmaceutical company always does is ty to get these trade agreements locked in to increase their monopoly power or their exclusivity periods and that essentially then becomes harder to change domestic law in the United States.

So, while the immediate impact will probably be in Mexico and Canada because they’re increasing the number of years of marked exclusivity, it also impacts the United States, because it makes it much harder to take these changes in the United States, and there are other provisions in the agreement which enable pharmaceutical companies to get easier patented rights on new uses of existing medicines; that is only going to increase the number of patents on existing drugs and we think that’s a fundamental problem, too.

Tahir Amin, DipLP, cofounder and director of intellectual property of Initiative for Medicines, Access, and Knowledge (I-MAK), explains how a recent trade deal could take a toll on biosimilars.