I think with biosimilar rituximab, we’re still waiting to see what the indication is. I think that's going to be a lot more of a pause. We know there’s a lot of discussion of the number of indications that these new therapies will have, especially in the broad range, for example, there may be patent protection issues. There will be a lot of discussion on what can be done for these therapies in the non-Hodgkin lymphoma setting and also maybe [acute lymphoblastic leukemia, ALL] settings as well based on the indication of the treatment. So, I think we’re all a little concerned about what’s going to happen with rituximab, the biosimilar coming out, what we’re calling the actual “skinny label” if you've ever heard that, sorry for the quotes everybody, but the skinny label is actually going to be a smaller FDA indication list that the biosimilar rituximab may actually have come out.

At this point I'm not aware of what's happening with FDA and also the current rituximab approval, but the key point is going to be what is FDA-approved based on this discussion, and also will payers—it's going to be a very unique if not pivotal discussion&mdash;will payers allow for off-label indications of the biosimilar as compared to the original product?

So what that means is you may only have 2 or 3 indications with rituximab, but the package insert with the approval on there for the original product carries 10. If those 8 are off-label, will payers allow for extrapolation to an off-label biosimilar product? [This is] very different from what we had before with the rituximab off-label discussion, which is actually you know, drugs are not approved an indication or Rituxan not being approved in the indication, but again studies being out there for efficacy. We're actually leading into a very unique direction of patent discussions, patent settlements, and also patent infringements, and how we're not there for some of those patent cliffs for this drug therapy.

We're really looking for some guidance in this area with payers. I think payers need to actually voice some of this discussion early on so we can kind of guide ourselves [on] what to do, because if we don't, we may need to actually have a brand-name drug therapy out there and also a biosimilar drug out there on the same shelf because payers may have different understandings of what that off label discussion will be from implementation of biosimilar rituximab.

So we're looking forward to it, but I think there needs to be a lot more discussion, upfront discussion, with payers at this point in time, because it may make a huge difference on our practice sites depending on how much rituximab they use.

Videos

Ali McBride, PharmD, MS, BCPS, clinical coordinator of hematology/oncology at the University of Arizona Cancer Center, describes imporant considerations in preparing for the arrival of biosimilar rituximab. 

Ali McBride, PharmD, MS, BCPS: Preparing for Biosimilar Rituximab 

What has been the impact of biosimilar adalimumab in the European marketplace?

For adalimumab, I think what’s worth highlighting—before we talk about the impact or anything, I think&mdash;for adalimumab, it’s a very unique situation. It’s something we’ve never seen before, and it’s rather unlikely that we’re going to see any such synchronicity in the launches.

For now, it’s still early days. We’re 3 months in. If you look at the overall European use of the adalimumab options, I think it’s probably been launched in half of the countries. In Germany, it’s been used to a higher extent over a shorter period than the previous biosimilars, showing greater confidence, greater acceptance.

It’s true that governments were very keen, and I think another unique feature of adalimuamb is not so much again the impact, but the way to the launches. While some governments have been preparing a lot for the lunches, the introduction of biosimilars, with adalimumab, it was extreme preparation. We’ve seen in the [United Kingdom] or Denmark really intense preparation, looking at all the features of the system that needed to be ready in time for the successful uptake, launches, introduction, and so on.

Julie Maréchal-Jamil, director of biosimilars policy and science at Medicines for Europe, describes early experience with biosimilar adalimumab in Europe.
 

Julie Maréchal-Jamil: Biosimilar Adalimumab in Europe

Concerns are mainly focused on switching from original to biosimilar, not only in terms of safety, or whether this treatment is good for me, but more it comes from a lot of misleading information and not enough contact with doctors. We are not discussing enough the issue of switching. Patients are getting to know that they were switched after [the fact]. It causes a lot of questions: why is the process not transparent enough? We really focus on patient education, and we’re trying to prepare different materials that everyone can educate themselves when patients start biological treatment.

Beata Ambroziewicz, president of the Polish Union of Patient Organizations and board member of the Polish Cancer Patient Coalition, discusses patients' concerns about biosimilars and the need for more education about switching.

Beata Ambroziewicz: Patient Concerns About Biosimilars

It depends on the kind of drug. If you look at insulin, it’s a very safe drug. It’s a small drug. It's a very safe drug, but you must follow patients who react. If you look at [tumor necrosis factor, TNF] blockers, infliximab, they have a chance for immunogenicity, so you have to follow them for a long time, but the discussion in the last session was [that] if a biosimilar is approved by [the European Medicines Agency, EMA], it is equally effective and safe, because all the aspects were researched during the registration process. So I think you must follow a patients, but not too intensively.

Anton Franken, MD, PhD, endocrinologist, discusses how closely patients who switch to biosimilars must be monitored.
 

Anton Franken, MD, PhD: Monitoring Patients Who Switch to Biosimilars

What kind of responsibility does the FDA have to assure providers and patients that biosimilars are safe and effective products?

So obviously, FDA play a clear role in educating all stakeholders around the misinformation [about biosimilars], but they also have an important role in terms of the confidence that they can instill in physicians and patients around biosimilars. These products undergo a rigorous review by FDA and patients and healthcare providers alike should be confident in their efficacy and the safety and the quality of the products. FDA could help us with that by reinforcing that confidence when new approvals are announced, for example.

Carol Lynch, president of Sandoz US and head of North America, discusses the FDA's role in instilling confidence in biosimilars.

Carol Lynch: Instilling Confidence in Biosimilars

Do you think there is potential to increase biosimilar uptake in the United States?

I think that the promise of biosimilars is still there for the US market. I think the savings potential is enormous and the ability to expand access for patients to biologic medicines is tremendous. There are estimates out there that for every day, for example, a biosimilar etanercept is not available on [the] market that it’s actually costing millions of doctors.

We actually got approval for Erelzi in August of 2016 and yet we’re still not allowed to market this product because we’re in litigation and we can’t bring it to market until that court case has been resolved. At this rate, it looks like it will be around $3 billion of savings that have been missed, and for patients in the system and for the healthcare system as a whole, I think that’s something that we all need to take on.

Carol Lynch, president of Sandoz US and head of North America, discusses the promise of the US biosimilars market. 

Carol Lynch: Future of the US Biosimilar Market

In efforts to address drug costs, some US states have passed legislation attempting to rein in drug prices. What are some of the common features of these laws?

When we talk about the states in contrast to the Congress, states have actually done an awful lot over the last 5-10 years on drug pricing, and it’s an accelerating trend. By one count, almost all of the states had some kind of proposals that they were considering last year [2017] and a number of them have been enacted.

I actually recently did an analysis where I counted 11 different categories, and we put out a client alert about it, 11 different categories of state actions on drug pricing. Everything from, kind of transparency-type rules where, if a product’s price is increased, it has to be reviewed by the state and potentially approved, to approval of importation from non—US jurisdictions, to repeal of “gag” rules where you walk in and the pharmacy has to tell you the cash price versus the price if you use your insurance, studies of drug pricing.

Many different experiments, if you will, where the states are taking a creative approach and in a lot of cases are actually enacting things. Now, some of these efforts are not without legal challenges. Some have already been successful, Maryland had a price-gouging bill that was struck down by the first court that heard it, and there will be others like that, but I think we are going to continue to see the states being very active in this area and having an impact.

James Shehan, JD, chair of regulatory practice at Lowenstein Sandler, LLP, discusses state laws targeting drug prices.

James Shehan, JD: State Efforts to Address Drug Costs

The US market is going to have to wait for biosimilar versions of AbbVie’s drug Humira because the AbbVie has accumulated a number of patents on the drug. In fact, our study found they have filed over at least 247 applications for Humira. Many of these will expire in 2037 and as a result of the stockpiling of patents that AbbVie has compiled, it is going to delay biosimilars in the market at least until 2023, and I think what’s important about that is that the companies that have agreed licenses with AbbVie to enter the market in 2023 will still be paying royalties, according to reports, to AbbVie. So those are going to go back to the consumer as well, even when biosimilars come to the market, and AbbVie’s chief financial officer has actually gone on record and said that they’re quite pleased with their patent and legal strategy and this is why we’re not seeing earlier entry of biosimilars in the US market.

I think it’s also worth saying the regulatory procedure under the [Biologics Price Competition and Innovation Act] in the United States is different to that in Europe, so getting a biosimilar version on the market in Europe is less onerous…and that’s also why we see a quicker uptake in the market in the European market. It’s also worth mentioning that the number of patents that AbbVie filed were considerably fewer; in fact there were 3 times as many patents in the US than there were in Europe and almost 4 times in Japan.

Tahir Amin, DipLP, cofounder and director of intellectual property of Initiative for Medicines, Access, and Knowledge (I-MAK), explains the role of patents in delays to US adalimumab biosimilar launches.

Tahir Amin: Why US Consumers Must Wait for Adalimumab Biosimilars

Who is responsible for addressing misinformation campaigns about biosimilars, and what can be done to stop them?

I think we all need to take on the task of tackling misinformation that’s out there, because I think, at best, it can lead to confusion for all stakeholders, and at worst, it can actually cause doubt about the safety and efficacy of biosimilars.

So, I think that from an FDA perspective they can definitely set out and help us with that. I think it’s on manufacturers to step up, but also the other players in the industry as well, so for example the medical societies, industry associations like [Association for Accessible Medicines] and Medicines for Europe, all play an important role in making sure that fair and balanced information is available to all stakeholders.

Carol Lynch, president of Sandoz US and head of North America, discusses which stakeholders have a role in addressing misinformation about biosimilars. 

Carol Lynch: Addressing Misinformation About Biosimilars

How would you characterize the state of biosimilar regulation today, and what have we learned from the first years of the Biologics Price Competition and Innovation Act (BPCIA)?

Biosimilar regulation, and this is something that I’ve been thinking about and active in for a long time in a previous role as head of government affairs at Novo Nordisk; we took a hand in shaping, you know, lobbying and negotiating, various pieces of the BPCIA.

It’s 2018, we have a law that’s been in effect 8 years, and I’d say only now are you finally starting to see real-world effects of the implementation. Fascinating, because you can always, as many people have, contrast it with Europe where they passed a law in the early aughts and within a year or 2 there were products on the market. And biosimilars to, I think, 7 different molecules by the time we passed our law and now they have many more. And we have a handful approved, and a very small number on the market. Patent challenges [are] holding up the others.

I think it is completely fair to say that FDA has been abominably slow in implementing the biosimilar law. The law puts significant hurdles in front of US biosimilars in order to get them to market. But that doesn’t mean that FDA had to take such a long time in rolling out guidances on some of these issues. And we’re still waiting, for example, on the guidance for interchangeability. I mean, not that much has changed scientifically in 8 years so what’s the hold up?

All that being said, there is a pipeline of products being worked on. I think you’ve seen some shakeout in the industry, you know you’ve got a little bit of a gold rush mentality early on and a lot of smaller players getting in who really don’t have the capacity, the capital, or personnel to solve the challenge—the rather difficult logistical challenge of developing a biosimilar. It’s essentially an effort that’s equivalent to bringing a new drug to market. So, you’re seeing some of those smaller companies going away, I saw Momenta recently laid off a bunch of their staff. It looks like a skeleton crew now, and they were a prominent early player, and there’s other examples like that.

You’re essentially seeing the big established industry—with a couple of newcomers like the biotech arm of Samsung playing a role&mdash;and litigation being an ongoing challenge to anyone trying to bring a product to market. See for example the Humira biosimilars that are approved and will not be launched until 2023 under various settlements with AbbVie.

James Shehan, JD, chair of regulatory practice at Lowenstein Sandler, LLP, discusses the state of biosimilar regulation in the United States.

Interviews