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.

Videos

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. 

Dr Marcus H. Snow: The US Launch of Renflexis

If the [Affordable Care Act, ACA] is repealed, what becomes of the [Biologics Price Competition and Innovation Act, BPCIA]?

So, the BPCIA is part of the ACA, and if Congress repeals it lock, stock, and barrel, without having some replacement ready to go, technically the BPCIA goes with it, right? I don’t think any of us expect that that’s going to happen, but I’ll tell you that with the current administration and with the current Congress, uncertainty seems to be the rule. The BPCIA so far, in all the debate that we have been hearing and monitoring in Congress and in the administration, seems to be flying completely under the radar. It does not appear to be one of the controversial aspects of Obamacare that the president and Congress are really focused on. From that standpoint, that’s good for biosimilar applicants, but again, because there is this uncertainty, we have at least been watching it. I think I can say that nobody really expects the BPCIA to go away, and we don’t think it is seriously at risk, but certainly we watch what Congress is doing in this respect.

Robert Cerwinski, JD, Partner at Goodwin, discusses what becomes of the BPCIA if the Affordable Care Act is repealed by Congress. 

Robert Cerwinski: Healthcare Reform and the BPCIA

Education is paramount with the implementation of biosimilars for pharmacists. Currently, there is an education gap because the FDA is finalizing the naming documents and how these drugs will be approved and make it to market. As more drugs become available, this gap will close, and pharmacists will become more used to seeing these in practice and utilizing these agents. They will become more familiar with the packaging differences, the naming, and the indications of use. So, they will be able to dispense these products with confidence.

Articles

Brandon Shank, PharmD, MPH, BCOP, Clinical Pharmacy Specialist, discusses the importance of pharmacist education on biosimilar treatments.

Dr Brandon Shank: Pharmacist Education on Biosimilars

Justice Breyer seems to be indicating that the FDA’s interpretation of the [Biologics Price Competition and Innovation Act, BPCIA] would be eligible for Chevron deference. And that might make sense with respect to the timing of the notice of commercial marketing. So, for example, the FDA might have some incentive in the future to say that they interpret the BPCIA to require 180 days between formal FDA approval at the expiration of the biologic exclusivity and commercial marketing.

But with respect to the civil procedure requirements—the “patent dance” aspect of the Sandoz holding, it’s not really clear what the FDA’s incentive would be or how the FDA’s authority would extend to parties’ standing before the Article III courts. It’s uncertain if the FDA has any incentive to weigh in on the patent dance, and whether they would feel confident that their interpretation of the procedural aspects of patent litigation would be entitled to deference, you know, Justice Breyer’s concurrence notwithstanding.

Ha Kung Wong, JD, Partner at Fitzpatrick, Cella, Harper and Scinto, discusses whether the FDA might clarify its stance on the BPCIA. 

Ha Kung Wong: The FDA's Role in Clarifying the BPCIA

Are there special considerations when using biosimilars in children?

Generally, no. Ultimately, in the pediatric realm, we end up having a lot of extrapolation of data and the biosimilars with the pediatric population should not be; ideally, this would be studied as much as it is in the adult world, but we just do not have that as often.

Marcus H. Snow, MD, Assistant Professor of Rheumatology, University of Nebraska, discusses the use of biosimilar treatments in children. 

Interviews