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.

Videos

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.

Tahir Amin: The US Trade Deal With Mexico and Canada and Its Impact on Biosimilars

How does the FDA plan to crack down on citizen petitions that are used to delay market entry of competitor products?

When we talk about the use of citizen petitions to impede or potentially affect the entry of competitive products in the marketplace, we’re talking about a narrower class of citizen petitions for which Congress actually enacted a separate provision of the statute, 505q. What that essentially says is there’s a citizen petition that is potentially going to delay a generic product, either an [Abbreviated New Drug Application, ANDA], a 505(b)(2), or 351k biosimilar, that FDA has to make decisions on those in an expedited fashion.

The FDA recently issued some guidance about changing the way that it views and reviews citizen petitions that come in to delay the entry of a generic drug into the market. What’s essentially said is given a lot more detail on how it will view those types of petitions and it has issued a set of criteria that it will look at in deciding whether one of these petitions has a primary purpose of trying to delay generic competition.

The agency has also said, if it makes that determination, that it’s going to refer the matter to the Federal Trade Commission for possible investigation of anticompetitive activities. Which FDA has done on at least 1 occasion regarding Shire and its vancomycin product where there were a number of citizen petitions submitted over a period of years.

James Shehan, JD, chair of regulatory practice at Lowenstein Sandler, LLP, discusses how the FDA plans to address citizen petitions that impede market entry of competitive products. 

James Shehan, JD: The FDA and Citizen Petitions

The updated guidance is inconsistent and it will create confusion and therefore create a safety problem. I think it’s still a possibility or hope that FDA will eventually park completely this guidance document and not apply suffixes anymore, and why we think that is because they have to take into account a number of realities. And what are those realitizes? Well, first is that FDA’s the only jurisdiction in the world which has used or applies suffixes—meaningless, unmemorable suffixes&mdash;to biosimilars and new biologics. And we believe that, because pharmacovigilance is a global activity and not only a national activity, that FDA should align with the highly regulated markets around the world, so that’s one important point of reality.

The second one, and it’s a very interesting one, is the fact that, I think it's in publication or an article of 2013, it was mentioned that we had 77 biologics on the US market which shared 23 nonpropritary names. In other words, because FDA does not apply the suffix to those products, it confirms that they don't consider that there is a safety issue or pharmacovigilance issue with biologics sharing the same nonproprietary name. And we share that with the FDA.

The other very important point is what happens today with the [adverse drug reaction, ADR] reports. When you go on the dashboard of the FDA website where they list the adverse events, somebody made the calculation, and looked every single biosimilar report, and found out that all ADRs which were linked to biosimilars have been identified to 99.1% with the brand name, so pharmacovigilance is assured. So, I think that's a very compelling point, and then maybe another important point is that I think FDA is working on a pilot project for track-and-trace, which will identify the products down to the batch number, and that’s the ultimate goal—that we identify down to the batch number&mdash;and a suffix can never do that.

From a personal perspective, because for IGBA, we have not yet finalized our comments to the FDA naming guidance, and we will do that, I think if FDA does not stick to what they have proposed now, I think they must apply the suffix also to all reference products for which biosimilars are approved. I even go further, and as I said, this is my personal opinion right now, and we’ll see if that will end up in our comment position, is that even for biologics for which which do not have a suffix now, but which undergo a manufacturing change and for which companies need to provide data to prove that safety and efficacy is not altered, that these products also need to retroactively have a suffix.

Suzette Kox, MPharm, Secretary General of the International Generic and Biosimilar Medicines Association (IGBA), discusses the FDA’s recent guidance on the naming of biosimilars, biologics, and interchangeable products. 

Suzette Kox, MPharm: The FDA's Guidance on Biosimilar Naming

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.

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.
 

Interviews