The issue is whether these biosimilars will achieve the goal of reducing prices in reducing healthcare costs. And in actual fact, data in Europe (again, they’re about 10 years ahead of us) suggest perhaps a 20% to 30% reduction in pricing when competitive by biosimilars are available in the marketplace.

We're too early to know whether we'll see that type of impact in the United States. If we do, even a 20% to 30% reduction in cost in a multibillion-dollar industry is a large amount of money, so it would be useful, but we don't know yet whether that will actually happen.

 this past year, looking at the early utilization of the hematopoietic growth factor biosimilars suggest maybe about a 10% reduction in price so far, but now we have 5 competitive hematopoietic growth factor biosimilars, we now have 4 trastuzumab or Herceptin biosimilars for breast cancer patients, so as we get multiple competitors in a class of agents, there should be more competition and hopefully a greater impact on price.

Videos

Gary Lyman, MD, MPH, of the Fred Hutchinson Cancer Research Center and Seattle Cancer Care Alliance, discusses how biosimilars could impact the cost of care.

Gary Lyman, MD, MPH: How Biosimilars Will Impact Price

This year for us is very special because we have European elections. It's a time when the political agenda gets quite reset for another 5 years, so it's very important and for us, it's important that the parliament that will be elected in May and then the European Commission that will be formed then in the fall all have a strategic agenda for health. That's very important for us, but more importantly that they have a reserved place for biosimilars to play an important role in that agenda.

Two points: I think, in Europe, there's a big focus on reducing inequalities in access, and biosimilars are very obvious and readily available to contribute to meeting that objective, so I think we're calling on the institution this year [in a very] big [way] to to have that strategic inclusion of biosimilars in meeting their health objectives.

The other bit is more on the industrial side of things, where biosimilars were born here in Europe because of how the system was set up early on, their legal framework and everything, but we haven't fared very well in manufacturing capability and know-how; that really needs to be nurtured because the the needs are growing in Europe and elsewhere, and I think it's important that we nurture that for the long-term.

So 2 agendas: one more on the equity, creating greater equity, and the other more on the industrial policy side. So this is our big agenda for 2019.

Julie Maréchal-Jamil, director of biosimilars policy and science at Medicines for Europe, describes opportunities for biosimilars in the year ahead.
 

Julie Maréchal-Jamil: Opportunities for Biosimilars in 2019

Nurses have been explaining to the patient what biosimilars are—some of the basic education that they are like generics, they have undergone enormous amounts of safety and efficacy as well as pharmacokinetic studies. So they really alleviate any concerns and anxieties that the patients have when we switch patients over, or when we start any new patients on the biosimilars.

Kashyap Patel, MD, explains the role that nurses play in educating patients about biosimilars.

Kashyap Patel, MD: Nurses' Roles in Biosimilar Education

Recently FDA has changed its guidances on how companies can make communications about their drugs and devices. There [are] actually 2 separate categories: one is economic information, like, for example, is a drug cost effective or how does it say, reduce the length of hospitalization, what kind of money does that save. The other one goes into what kind of communications, what things that companies say that are consistent with the labeling of a product.

Both of these guidances essentially have slightly liberalized what companies can say by giving companies more guidance on what is permissible and what is impermissible. The healthcare economic one, in particular, companies really wanted to see because there have been 2 laws in the last 15 years where Congress asked FDA to do more in that area and give more guidance.

So that one is great now because now we know particularly prior to approval for example, that you can go and talk with payers and show more data about what has this product done in clinical trials.

James Shehan, JD, chair of regulatory practice at Lowenstein Sandler, LLP, discusses the implications of recent FDA guidance on medical product communications.

James Shehan, JD: FDA Guidance on Medical Product Communications

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.

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.

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