Charles Bennett, MD, PhD, Discusses Hurdles for Biosimilar Adoption

The Center for Biosimilars^® (CfB): I'm Tony Hagen, senior editor for The Center for Biosimilars^®. Today, we're talking with Charles Bennett, MD, PhD, a hematologist and oncologist and professor in the Clinical Pharmacy and Outcome Sciences Department of the College of Pharmacy at the University of South Carolina. Dr Bennett served as lead author on a recent paper about the progress of oncology biosimilars.

In part 2 of this interview, we talk about pay-for-delay agreements that arise from inter partes reviews of originator drug patents and their validity. Bennett explains that there's a significant anticompetitive practices factor involved that requires the involvement of the FTC [Federal Trade Commission]. Biosimilars are failing to launch because of these issues, he says. We also talk about the unique Japanese consensus-building method of reviewing biosimilar applications and how distinct this is from the way the United States does things. Dr Bennett also had interesting things to say about the need for biosimilar education and savings.

CfB: In the 3 regions that your study focuses on, the United States, Japan, and the European Union, you saw that they all started approving oncology biosimilars roughly around 2016 and 2017. It’s often said that the United States is far behind the European Union in biosimilar approvals. What is your take on where the US is competitively in that area?

Bennett: 2015 is when the [biosimilar approval] legislation passed and we had first approval in the United States [Zarxio, filgrastim]. And then in 2017, around the world, that's when these drugs began appearing both in the US, Europe, and Japan. I picked those 3 countries because they are the 3 largest marketplaces for biosimilar drugs. They all appear around the same time.

Then, we looked at [some of the barriers] to launching biosimilars. What I was doing in this paper is a policy review of barriers to launch. I'm not worried about the price; I'm worried about the launch. And we found, at the end of the day, that there were significant barriers to launch in the United States that differ from those in Japan and Europe. The kinds of things that are barriers [are things like] the regulatory barriers. Those are real barriers. Even when you do get approval, there are these patent litigations. We looked through the European patent law offices and they do not view as many patent-law cases as the US does.

It’s hard to know whether pay-for-delay is good or bad for biosimilars. Let's be clear about that. The naïve answer is that it's a bad idea; but it may be, in fact, that the people who are paying for delay do not have a viable patent and [biosimilar developers are] being paid for delay because [originator companies] might not make it to the court system. It's hard to say.

Amy Klobuchar [D-Minnesota] has introduced legislation to get rid of pay-for-delay for generics and for biosimilars. The issue for pay-for-delay for biosimilars is not the same as the issue for pay-for-delay for generics. Biosimilars [require] a heavy amount of technology and when you pay-for-delay, it is suggested that you may not have enough bandwidth to get through a patent litigation. That does not happen for generics. So, understand that pay-for-delay might have to be adjudicated more closely in some areas.

CfB: In your study, you noted that there's strikingly less litigation in Europe than there is in the United States. How is Europe handling biosimilars litigation that is making it easier for them to get biosimilars to market?

Bennett: [In Europe,] if you have a patent concern, you have to go country-by-country. So, in the European Union, you have to do 27 different lawsuits to raise a patent litigation [lawsuit]. That's a lot of money, a lot of time, and a lot of complexity. So, [reference manufacturers] don't do that.

The other thingwith patent litigations is that you cannot initiate a patent litigation unless you have a product where you worry about the patents, whereas with inter partes reviews, anybody in the world can bring up an inter partes review. And there has developed this new economy in Washington, DC. Lawyers will file inter partes reviews on these reference drugs without even being referred to by the biosimilar maker and you don't have to file it when the biosimilar maker gets approval. These inter partes review challenges have become a place where people get bought off. So, you pay money for the inter partes review to go away, because you don't want to deal with those people. It's a whole new level of hurdles, that is unique to the United States. For these inter partes reviews, these patent reviews, if you talk to any of the most senior biosimilar investigators in the United States, they are in the middle of every one of these cases as expert witnesses.

CfB: Maybe we should do the same thing. We should break the United States up into 50 different units.

Bennett: Inter parties reviews historically started in 2012 because of Microsoft. Microsoft did that, and it was a way to protect their technology and their patents. They had these inter partes reviews, and there were people who were challenging Microsoft patents. It was not meant to be used for biosimilars.

In 2015, when [reference manufactures] realized these could be used for biosimilars, if you look at the graph, it looks like the coronavirus graph if it was in 2015. It's just going up like crazy. The legal aspects of biosimilars are a financial burden and a financial hurdle and it has to be fixed by either improved legislation or improving the Federal Trade Commission—have them step in more often. Either way, it has to be done through the legislative branch or through a regulatory fix.

CfB: Does this spike in inter partes review litigation partly account for the falling behind of oncology biosimilar approvals in the United States?

Bennett: [It accounts for] failure to launch. So, just because you get an approval doesn't mean you can sell the drug.

CfB: Currently, there are 6 adalimumab biosimilars approved in the United States, all of which will not be able to enter the market until at least 2023 because of legal actions by AbbVie, the manufacturer of the reference product, Humira. Can you discuss the impact of these actions and what needs to be done?

Bennett: Rituximab [Rituxan] has done the same thing. Amy Klobuchar has the idea of making it illegal. There's going to be policy on both sides, and this is when lobbyists will go to Washington, DC, and they're going to be there to see whether she can get these things through or not.

That's why I personally have been advocating for the Federal Trade Commission to become more actively involved, and to review these pay-for-delay contracts, one at a time. So, instead of a big new law, which I think is going to be misguided, you go to those 5 FTC commissioners to see if they can look at each of the various pay-for-delay [agreements] and make a decision on whether they were appropriate or inappropriate.

CfB: Your paper notes that oncology biosimilars have a savings potential of $110 billion by 2029 in the European Union, Japan, and the United States. Is this realistic?

Bennett: Last time they said that $54 billion [savings could be achieved], and we said that was an over call; $110 billion, again, is an overcall. Unless you fix the system, we're not going to get that $110 billion. And what we showed in the paper is that there is a tremendous amount of barriers to launch that were far more than the simple barrier of educating doctors and educating patients. We've talked about the hidden rebates that need to be addressed and dealt with. We've talked about the approvals. We've talked about the quality of the product. And we've talked about the litigation around the products. At the end of the day, the fixes in the United States need to be very aggressive and they need to be on point. Otherwise, we're not going to get $110 billion [in savings].

To watch part 1 of this interview, click here.