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

Could the STRONGER Patents Act impact biosimilars?

That's an interesting act, actually. My understanding is that the STRONGER patents act, among other things, proposes to harmonize the burdens and claim construction standards between PTAB, the Patent Trial and Appeal Board, that hears IPRs, and the district courts that hear district court litigations. In particular, the bill proposes to change the burden of proving invalidity in IPR and a related action, called a PGR, or a post-grant review, to the clear and convincing evidence standard and to use the narrower ordinary meaning claim construction standard that is used in litigation. In other words, it would change the burdens and standards to match what you see in litigation.

The bill would also limit standing to those who had been sued by the patent owner. So it kind of limits who would have standing as well to actually raise the IPR.

Another thing that it does is that it allows for appeal of an institution decision, which is something that you don’t have today. Today, an institution decision, whether [an IPR] is instituted or not is not appealable. So this would give you another shot at saying the PTAB was wrong in instituting an IPR. Given the estoppel provisions already associated with IPR and PGR, these changes could greatly reduce the popularity of these proceedings.

Although in a macro sense, it’s possible that having more restrictive paths to invalidating patents may mean that some biosimilars take longer to clear the necessary IP to launch risk-free, It’s unlikely that this legislation, the STRONGER Patents Act, would affect the ability of biosimilars to reach the market. In some ways, due to the size of most biologics patent portfolios, a biosimilar company may even prefer going to district court where they can challenge a number of patents all at the same time.

Videos

Ha Kung Wong, JD, partner at Fitzpatrick, Cella, Harper and Scinto, discusses how the STRONGER Patents Act could affect biosimilars. 

Ha Kung Wong: Biosimilars and the STRONGER Patents Act

Might Congress revisit the Biologics Price Competition and Innovation Act (BPCIA)?

In the small-molecule pharmaceutical context, we saw Congress reform the Hatch-Waxman Act several times as procedural issues arose. For example, the Hatch-Waxman Act was amended in 2003 to address some patent listing and enforcement strategies issues. If we continue to see the same sorts of issues arise, or, for example, if we see a number of at-risk launches that end with biosimilar injunctions, Congress could well decide to amend the BPCIA. But one thing I don’t like to predict is what Congress will and won’t do. I think many have tried in the recent past and very few have been accurate.

Ha Kung Wong, JD, partner at Fitzpatrick, Cella, Harper and Scinto, discusses whether Congress might revisit the Biologics Price Competition and Innovation Act (BPCIA).

Ha Kung Wong: Congress and the BPCIA

Does a designation of an innovator product as a drug as opposed to a biologic make it easier or harder to enter the market with a follow-on?

It really depends on the specific product you’re talking about. In some cases, it could be easier, in some cases it could be harder. I will say upfront that very soon, in 2020, all those products, like insulin, which are now regulated as drugs and get approved through NDAs and 505(b)(2) applications, they’re all going to be transitioned to biologics and they’re going to have to submit BLAs.

So, this issue won’t exist for much longer. But again, given the current state it really does depend on the particular drug involved. So for products like insulin that are currently regulated as drugs, there are two pathways to get approval of a “generic.” There’s the NDA pathway and the 505(b)(2) pathway. I think a lot of these products are probably so complex that the NDA pathway isn’t a very realistic possibility.

The FDA will take the position, and has taken the position, that you can’t really demonstrate that the active ingredients are the same. On the other hand, if it were regulated as a biologic and you could do a biosimilar, biosimilars don’t have to be identical. In that sense, it might be easier for some of these products to get approval as a biosimilar because you don’t have to show the level of identity that you do to get an ANDA. The other thing is that biosimilars can be supported by clinical data whereas NDAs cannot. I guess the third issue that folks need to look at is the level of exclusivity. Biologics have 14 years of exclusivity, so if you’re blocked by that, that’s going to be a lot longer than you’d be blocked if the product were subject to an NDA. The longest exclusivity period is 5 years, and even adding on the delays for potential patent litigations, the most it’s going to be is 30 months. In some cases if you’re looking at a reference product that has the 14 years of exclusivity, you’d probably prefer that it were regulated as a drug rather than a biologic.

Scott Lassman, JD, partner in Goodwin's Technology and Life Sciences Group, explains differences between follow-ons and biosimilars.

Scott Lassman: Follow-On Products Versus Biosimilars

When the FDA waives the requirement of a single shared REMS system, what additional burden does that waiver place on the FDA?

A waiver of a REMS doesn’t really add a burden to the FDA. There may be a small burden because they’ve got to review and approve 2 different REMS, but the work it takes to help companies agree to a single shared REMS I think is at least as burdensome for FDA as reviewing and approving 2 REMS. I think where the real burden lies, and this is where FDA’s main concern is, is on the healthcare system. For instance, pharmacies and hospitals, they may get used to brands REMS and then all of a sudden, a generic is approved and if it has its own REMS, now you’ve got 2 different REMS that you’ve got to try and juggle. I think pharmacies don’t like it, physicians don’t like it, hospitals don’t like it, and I think that’s where FDA’s real concern is and why they’ve been so hesitant in a lot of cases to waive the single shared REMS requirement. 

Scott Lassman, JD, partner in Goodwin's Technology and Life Sciences Group, explains the burden to the health system when FDA waives a single shared REMS requirement.

Scott Lassman: Waiving the Single Shared REMS Requirement

Do you have any concerns about using biosimilars in patients with IBD?

As far as biosimilars are concerned, or for that matter any kind of generic medication, there’s always a concern in clinicians. There are certain guidelines that the biosimilars have to follow, but still there can be a difference between them and the brand-name product. What we do in primary care is try a biosimilar, and if it seems like it’s getting us the same effect that we want, we’ll stick with it. But [for] those that don’t work so well, those that let’s say they fall short, whether it’s with side effects or efficacy, we keep those in our minds, and we tend not to go to them, and we do the brand name products.

Paul P. Doghramji, MD, FAAFP discusses using biosimilars in practice.
 

Dr Paul P. Doghramji: Using Biosimilars in Practice 

Are you or any of your colleagues beginning to prescribe biosimilars?

I haven’t started prescribing biosimilars yet for these diseases. I tend to use brand names more than anything, but sometimes I’m forced to do it because of insurance constraints. As a general rule, we like to use a medication that’s come out by that specific pharma company in that brand name because we know exactly what we’re getting.

Paul P. Doghramji, MD, FAAFP, discusses whether he has begun to prescribe biosimilars for patients with inflammatory bowel disease.
 

Dr Paul P. Doghramji: Prescribing Biosimilars in IBD

Do you see biosimilar treatments as playing a role in controlling the cost of care?

I think we’ve already seen biosimilars act as a cost-leveraging mechanism. If you look at the average sales price of original anti—tumor necrosis factor drugs, and you look at the entrance of biosimilars into the marketplace, you can see a definite competitive trend, so there is a lot of competition in this space and that is causing [average sales prices, ASPs] to go down. I think that as the field continues to grow, you’ll see more of this.

I would say that our position is that patients who are on a particular agent should remain on that agent if they’re getting efficacious therapy, because "biosimilar" does not mean "same molecule." For new starts, I think that it should be a level playing field and the competition should be on the basis of both price and service delivery as well as known outcomes. However, I think that on existing therapy, our first duty is to keep the patient safe. But overall, in this field, biosimilars will act in a market force the way other market forces have caused competition to adjust price. We’re seeing that in the marketplace and we think that’s good for the American public.

Ira Klein, MD, senior director of health care quality strategy for the strategic customer group at Johnson & Johnson Health Care Services, explains how biosimilars will help to control costs.
 

Dr Ira Klein: Biosimilars and the Cost of Care

Do you see biosimilars having a role to play in [the Oncology Care Model, OCM]? 

I do, and I don’t think we know yet how much cost savings will be involved with biosimilars, but we know it will be some. I think it will start around 15% and go up to 30%, maybe more. I think that the experience in Europe is 30%, 50% is high. The biosimilars are in a space that- so Genentech is biosimilars and is going to be impacted by biosimilars, so about a third of our spend is Genentech products, so if you reduce a third of your spend even by 10%, 15%, 20%, it’s a big number. So, we see biosimilars being very key to saving in OCM.

Jeff Patton, MD, president and CEO of Tennessee Oncology, discusses how biosimilars fit into the Oncology Care Model (OCM).

Dr Jeff Patton: Biosimilars and OCM

What are REMS programs, and why are some stakeholders concerned about them?

A: REMS programs are safety programs that, again, were enacted back in 2007 and they are designed to allow the FDA to approve a drug even if it might have some safety issues that typical risk mitigation programs can’t address.

For drug products, the main way that FDA reduces risks is by identifying them on the label so that physicians know what the risks are and can take appropriate steps with their patients. In some cases, maybe not give a particular medication to a patient if the risks are too great. I think the conclusion FDA came to is that they can’t really trust physicians. Physicians don’t read the label and will use medicines even when the label says they shouldn’t be used. [The FDA] asked congress for the authority to take stronger measures, and 1 of the measures they got was a REMS.

The REMS provisions allow FDA to impose things like distribution and use restrictions. For instance, it might require special training for a physician to be able to prescribe the medicine, or it might say you may only use it in a certain facility as safeguards. They did really restrict how a medicine can be used and distributed. The concern folks have, particularly biosimilar manufacturers, is that brand companies that have drugs that are subject to a REMS are using them to prevent generic competition. They do that in 2 ways: the first is to restrict samples of the brand. So if you’ve got a generic product or a biosimilar, you need to get samples of the brand so you can conduct your tests. For a generic, it’s bioequivalence tests, [and] for a biosimilar it’s to show biosimilarity. But the brands are essentially saying, “our product is subject to a REMS. We can’t give it to you because it just doesn’t comply with the REMS requirements.” That prevents companies from doing the testing that they need to submit the application.

The second concern is that, and this is just for generics, not for biosimilars, but for generic products there’s a requirement that the generic, if it gets approved, must have a single shared REMS. It must essentially share the REMS that the brand already has. A lot of times, companies will delay agreeing, and the generic cannot get approved unless it has a single shared REMS. The concern is that you’re supposed to negotiate with a party that really has no interest in agreeing with you, and [those are] the main 2 concerns with the REMS.

Scott Lassman, JD, partner in Goodwin's Technology and Life Sciences Group, explains why REMS programs give biosimilar and generic drug developers cause for concern.

Scott Lassman: REMS Programs and Biosimilar Therapies

Why are Citizen Petitions to the FDA so controversial?

I think they’re controversial because people don’t understand exactly what they do and what they’re used for. Petitions, as the name implies, can be filed by anybody. They can be filed by citizens, they’re often filed by public interest organizations, but pharmaceutical companies also submit them and I think the concern is that they will submit them primarily to delay generic competition.

That might have been true in the past, but the law was changed back in 2007 to prevent that. The law currently says that the FDA review of a petition goes along one level and the review of the application, or the abbreviated new drug application (ANDA), goes along another. A petition cannot delay an approval of a generic application unless there’s a public health issue. The FDA actually puts out data every year about how many petitions are filed, how many will delay applications, and if you look at FDA’s own data, less than 1% of generic applications are delayed because of a petition.

The problem is really more of perception, and I think the issue is that there’s a lot of bad information out there. There have been a number of press reports, and actually academic publications, which purport to analyze petitions and have come up with the claim that they actually do delay generic competition. But, all of these publications, when they do their analyses, they rely on a lot of assumptions and they actually ignore FDA’s own data. I personally file a lot of petitions myself, so maybe I’m a little bit biased, but I’ve never had a petition that delayed a generic application. They raise issues, a lot of times the companies that submit them have the most information about the product, so they raise these issues with FDA, FDA considers them, but I think in very, very few cases, and only when public health is potentially involved, will it actually delay FDA’s decision on an application.

Scott Lassman, JD, partner in Goodwin's Technology and Life Sciences Group, explains why Citizen Petitions to the FDA are so controversial among generic and biosimilar stakeholders. 

Interviews