 have an impact on litigation for biosimilars?

 decision applies to patent infringement litigation, generally, and it concerns the patent venue statute. The issue in

 is: where can a patent infringement suit be brought against particular defendants?  Before 

was decided, the Federal Circuit had taken the position that anywhere that a defendant was subject to personal jurisdiction, either personal jurisdiction because it was the place where the defendant was incorporated, or had his principal place of business, or because there was specific personal jurisdiction, i.e. where the acts of jurisdiction occurred. The Supreme Court took a narrow view of the venue statute, or the venue provision in the patent statute, and said really a suit can only be brought where the patent defendant resides or where the acts of infringement have occurred and the defendant has a regular established place of business. The dispute in

was really: what does “reside” mean?  The Federal Circuit had taken the position that it’s anywhere the personal jurisdiction lay, and the Supreme Court said it’s just where the defendant is incorporated. So, the upshot of all of this is where particular defendants can be sued is now more limited in the context of patent infringement litigation. Interestingly, the Supreme Court did not weigh in on where foreign defendants can be sued. So, foreign defendants that aren’t really incorporated anywhere in the US—that question remains unanswered. As the reference product sponsors and biosimilar manufacturers jockey over where suits under the BPCIA should be adjudicated, which venues may be more favorable to the biosimilar applicant versus the reference product sponsor, now 

 is going to limit some of those choices.

Videos

Robert Cerwinski, JD, Partner at Goodwin, discusses the impact of the recent Supreme Court ruling in TC Heartland v Kraft on biosimilar litigation. 

Robert Cerwinski: The Impact of TC Heartland on Biosimilar Litigation

Could 4-letter suffixes to the names of biosimilars create confusion? 

I think one benefit of the naming system is that you know what the reference product is. I think some clinicians, pharmacists included, and patients may assume interchangeability, which may not be inferred by the naming system. I think it is important to have a way to differentiate these products so that you can know which ones are interchangeable, so that ones with different indications will also be recognized and not be used for the wrong indication. Also, dosing and administration differences in products may also be assumed with the naming system, which is why the suffix will be helpful in those situations. I also believe that with this naming system, they need to differentiate the products in the computer order systems and be able to have adverse event reporting that distinctly identifies them, which the naming system will with the current suffix system.

Brandon Shank, PharmD, MPH, BCOP, Clinical Pharamcy Specialist, discusses the merits of the current biosimilar naming system.

Dr Brandon Shank: Biosimilar Naming and Suffixes

What would be the impact of biosimilars on Part D drug pricing? 

So right now, our country is facing a drug price explosion. There’s been a couple of areas where it’s growing fastest—the hematological space, where we’re growing about 12.9% per year in terms of cost, and in the oncologic space, [which is] growing at 4.9%. So, we don’t have infinite resources, and at some stage, the system with either implode, or we have to look at drug pricing. Biosimilars do have a role. They can help in reducing some of the additional escalation of the expenses. When we go back and look at the European experience, in Europe, in 10 years’ time, drug prices have dropped by about 30% compared to the reference product. So clearly biosimilars do have a significant role that they can play in the Part D drug pricing space, and they also improve access as well, so biosimilars have a very valid and legitimate space in becoming part of the solution for Part D prices.

Kashyap Patel, MD, Medical Oncologist, Carolina Blood and Cancer Care, discusses the potential impact of biosimilar drugs on Medicare Part D drug pricing. 

Dr Kashyap Patel: Biosimilars and Medicare Part D Drug Pricing

Do you have concerns about automatic substitution of biosimilars for reference products? 

Yes, I do and I guess I don’t, to some degree. I do have [concerns with] automatic substitution, but it depends on who is doing the substitution and what is being substituted. If I place someone on a new medication and instead of getting the bio-originator product, I get a biosimilar as my first medication, right now I have no qualms about that. The patient is starting on a new medication, it is what it is, and we will see how they respond. However, if they are already on a bio-originator product and they are switched over, I have some concerns about switching a patient who is doing well. The third avenue where you could see switching, which I would be very opposed to, would be someone who is on medication—we’ll say etanercept&mdash;and the insurance company or the payer decides that adalimumab biosimilar is the medication of choice. Switching a patient from one drug, not only to a biosimilar, but to a biosimilar of another medication, has huge implications and is very concerning for me. As a rheumatologist, the problem with rheumatoid arthritis is that early on, we have joint damage, and if you lose control of the disease activity, in the long run you can see worse outcomes with increasing rates of disability, etc.

Marcus H. Snow, MD, Assistant Professor Rheumatology, University of Nebraska, discusses concerns about automatic substitution of biosimilars for reference products. 

Dr Marcus Snow: Automatic Substitution of Biosimilars in Rheumatology

Janssen is currently involved in litigation over infliximab. Where does the case stand?

Right now, the parties are actively litigating potential infringement of 1 patent. The parties were scheduled for a trial, and that trial has been suspended while the parties litigate issues concerning standing and damages. Right now, there is a pending motion to dismiss Janssen’s complaint for patent infringement for lack of standing. The allegation that has been announced publicly is that Janssen doesn’t have all the rights it needs to assert the ‘083 patent against the defendants, and therefore the suit should be dismissed. That’s where things stand right now. There are some pending damages issues as well, that the court is considering, but it’s really that motion to dismiss that the court is hearing briefing and arguing on.

Robert Cerwinski, JD, Partner at Goodwin, discusses current infliximab litigation.

Robert Cerwinski: Current Infliximab Litigation

What are some considerations in the labeling of biosimilars?

The biggest consideration in biosimilar labeling is the fact of extrapolation. Extrapolation relates to the fact that a biosimilar that may have a half-dozen specific disease indications, will likely only be clinically tested in 1 of those indications. If it is proven to be equivalent by all the different measures the FDA is using, then the FDA appears to be granting, by extrapolation, the expanded label to all indications. So, there is a big difference from a branded drug, which had to have clinical trials in each of the 6, to a biosimilar which is only going to have a clinical trial done in 1 of the 6.

Bruce A. Feinberg, DO, CMO, Cardinal Health Specialty Solutions, discusses biosimilar labeling and concerns with extrapolation. 

Dr Bruce A. Feinberg: Biosimilar Labeling and Extrapolation

Can we expect to see an executive order on drug pricing in the coming months? 

You know, I think the executive branch is a little bit at odds with itself. We are not really sure from one day to the next what the priorities are going to be, and with all of the debate right now over Obamacare, I really cannot say that we can predict that with any degree of certainty. I think all that we can predict, when it comes to healthcare, is that the executive branch is going to continue to surprise us.

Robert Cerwinski, JD, Partner at Goodwin, discusses the potential for an upcoming executive order on drug pricing. 

Robert Cerwinski: The Potential for an Executive Order on Drug Pricing

What are some recent trends in [Patent Trial and Appeal Board, PTAB] decisions concerning biologics and biosimilars?

We see that biosimilar manufacturers have really embraced the availability of [inter partes review, IPRs] as a mechanism. Well before the biosimilar applications are actually submitted to FDA, we see that biosimilar manufacturers are really trying to clear a path with key patents well before they actually get to FDA. That’s a definite trend that we see in biosimilars. We had expected that IPRs would be important to biosimilar manufacturers, given the sheer number of patents and the variety of patents that typically cover reference products, especially products like Humira where there is a veritable patent thicket protecting it, and indeed that’s what we’ve seen. Most of the IPRs that have been filed to date have really centered on 3 products: Herceptin, Rituxan, and Humira. So, 3 of the biggest biologics that are really amenable to biosimilar applications at this point. Over a dozen of IPRs have been filed with respect to each of these products and the patents that cover them. Those are the big 3 for IPRs.

In terms of what’s actually happening at the PTAB with these biologic-related IPRs, we see that the rate of success for petitioners has been somewhat lower than what we’ve observed for petitioners generally. It’s a complex area of technology and we’re seeing that the PTAB is being very careful and meticulous in its approach to institution decisions as well as its approach to final determinations. So we’re seeing a lower rate of institution for biosimilar-related IPRs than in general. For those petitions that are instituted, we’re seeing a somewhat lower rate of invalidation after final determination. And in terms of patents that fare better or worse, if you are a petitioner in the PTAB, we see that method-of-use patents, so patents that cover approved indications, institution is granted somewhat more often for those kinds of patents than for composition patents or formulation patents. The data set isn’t very large for this yet, but we do something of trend in that respect, and that holds true in final determinations as well; we see that the PTAB, at least currently, has been more willing to hold method-of-use patents invalid. I think we are also seeing—I use the word “meticulous”&mdash;I think the PTAB is really trying hard to get these petitions resolved correctly. They are being&mdash;I use the word “sticklers”&mdash;they are holding everybody to the rules and they are holding everybody to their burdens of proof in these petitions pretty rigorously.

Robert Cerwinski, JD, Partner at Goodwin, discusses the “big 3” biologics for inter partes review: Herceptin, Rituxan, and Humira. 

Robert Cerwinski: Recent Trends in PTAB Decisions on Biologics, Biosimilars

Ha Kung Wong, JD, Partner at Fitzpatrick, Cella, Harper and Scinto

What are current litigations that could impact biosimlars?

I think I’ve got to give a little bit of background there. To date there have been about 10 [Biologics Price Competition and Innnovation Act, BPCIA] cases filed give or take, and several of these actually addressed similar procedural issues to those in 

, so a lot of those have already been covered. Initially, as an example, several biosimilars applicants took the position that if they complied with the patent dance, they were not required to provide the 180-day notice of commercial marketing. In 

, the Federal Circuit ruled that the notice of commercial marketing, that provision, is always mandatory and enforceable by injunction. So that’s basically all resolved.

Now the nature of the disputes is starting to look at more specific requirements of the BPCIA. For example, several biosimilar applicants have provided their aBLA (their abbreviated Biologic License Application), but not manufacturing information, as required by the statute. In 

, the district court held that the only remedy under the BPCIA for the reference product sponsor under those circumstances is an infringement action, and not declaratory judgment. In 

, the district court found that because the defendant had not complied with the patent dance, the plaintiff’s damages would not be limited to a reasonable royalty despite the fact that the patent in question was not asserted until more than 30 days after the patent dance was completed. So as parties are getting more experience with the BPCIA, we are seeing some more procedural issues being clarified.

In terms of non-BPCIA cases, though, the most important case right now is probably 

, which concerns the availability of permanent injunction in drug patent disputes. Amgen and Sanofi market competing anti-PSKC9 inhibitor antibodies for controlling cholesterol. Their products are the only drugs in that class. The district court granted a permanent injunction, which the Federal Circuit temporarily stayed pending the outcome of Sanofi’s appeal. Depending on the outcome of 

, we may see the stakes get significantly higher for biosimilar applicants considering at-risk launches.

Ha Kung Wong, JD, Partner at Fitzpatrick, Cella, Harper and Scinto, discusses current BPCIA litigation concerning biosimilar products. 

Ha Kung Wong: Current BPCIA Litigation in Biosimilars

What are your thoughts on the recent launch of Renflexis in the United States?

I think that it will be very interesting to see what happens now that we have 3 versions of infliximab on the market. Will this drive the cost down? I think that it remains to be seen. I think, as you look at what has happened since the first biosimilar for infliximab has hit the market, you have seen insurance companies—United, for example, actually signed a contract with Remicade to stay with the bio-originator. I think you are going to see some of this, but I think it will be interesting to see the uptake and how this happens, and I think we will start to see the outcomes of this moving forward.

Marcus H. Snow, MD, Assistant Professor Rheumatology, University of Nebraska, discusses the recent launch of a new biosimilar infliximab, Renflexis, in the United States. 

Interviews