Hi, I’m Skylar Jeremias for The Center for Biosimilars®, your resource for clinical, regulatory, business, and policy news in the rapidly changing world of biosimilars.

The European Hematology Association recently held its 25th Annual Congress, EHA25 Virtual, from June 11 through June 21. The meeting was conducted on a digital platform due to the coronavirus disease 2019 (COVID-19) pandemic and featured some key study findings and presentations on the up-and-coming world of hematology biosimilars.

The following is a summary of our biosimilar coverage from this event:

Investigators produced what they described as the 

 the use of biosimilar erythropoiesis-stimulating agents (ESAs) in patients with myelofibrosis (MF)-related anemia.

Investigators said ESAs are used to manage anemia in hematological malignancies, but scarce evidence exists for the use of these agents in the treatment of MF, and available results are divergent: Response rates range from 23% to 69%, according to the abstract presented at EHA25 Virtual. Until this study, there were no data on the use of biosimilar ESAs in this setting, investigators said.

Investigators reported an 88% overall response rate for a Sandoz rituximab biosimilar in combination with chemotherapy in patients with CD20-positive diffuse large B-cell lymphoma. At the end of treatment, the complete response was 57% and partial response was 31%. Investigators said 61% and 29% of patients experienced enlarged lymph nodes and disease-related pain, respectively.

 presented this month at EHA25 Virtual confirmed findings from the REFLECT study released in 2019, which was the first prospective postapproval study to evaluate a rituximab biosimilar in this context.

 that a rituximab biosimilar developed by Celltrion Healthcare (Truxima) in combination with lenalidomide and acalabrutinib (R2A) in patients with relapsed or refractory aggressive B-cell lymphoma was tolerable and effective.

The addition of rituximab, a targeted therapy, to chemotherapy agents can improve patient outcomes but adds to the financial burden of treatment. Investigators said that exploring the use of biosimilar rituximab may be an avenue to bring down costs.

To read all of these articles, visit our EHA 

Videos

Here is a summary of our coverage from EHA25 Virtual, the annual meeting for the European Hematology Association (EHA).

EHA25 Virtual Roundup

The Center for Biosimilars® (CfB): Hello, I'm Matthew Gavidia. Today, on the MJH Life Sciences News Network, The Center for Biosimilars® is pleased to welcome Christine Simmon, executive director of the Biosimilars Council and senior vice president of policy and strategic alliances at the Association for Accessible Medicines (AAM). 

Can you tell us a little bit about the Association for Accessible Medicines and your role with them? 

Hi, Matthew, Thank you for having me today. The Association for Accessible Medicines represents the makers of generics and biosimilars, and our mission really is to provide patient access to these more affordable alternatives to expensive brand medications. So, what we do is we advocate on behalf of the manufacturers and help create a conducive legislative as well as regulatory and legal environment for these manufacturers to produce the products for America's patients.

CfB: What are some key pieces of legislation that the AAM is supporting to advance the use of biosimilars?

AAM's work on biosimilars takes place through a division called the Biosimilars Council. So, the Biosimilars Council has a membership and we are pure play biosimilar manufacturers who are out there advancing biosimilar versions of innovator biologics, and we are very active on the advocacy front supporting pieces of legislation generally designed to further incentivize payers and patients to increase biosimilars utilization in the United States.

So, to help get these biosimilars really into the hands of patients, we are trying to, in addition to our usual education efforts, we are using legislative fronts to provide additional incentives for providers to prescribe these medicines to their patients. For example, we want to increase physician reimbursement for Medicare Part B. Right now, providers in Medicare Part B receive an add-on payment of plus 6% of the [reference] biologic’s average sales price (ASP) and we want to increase the add-on payment to 8% of the ASP, but it would only apply if the biosimilar’s price is lower than the [reference] biologic's price.

And so, this piece of legislation, which is called the BIOSIM Act, has bipartisan support in the House and is also included in the Senate Finance package and the Democrat House package, HR-3. We also are trying to eliminate biosimilar cost sharing in Part B.

So, these Part B efforts take precedence because biosimilars that are currently on the market are reimbursed through Part B and they're physician or hospital administered. Eliminating cost sharing would help beneficiary access to biologic treatments and encourage physicians to also prescribe them for their patients.

Right now, in Part B patients pay less for biosimilars compared to [reference] biologics because the ASP for the biosimilar is on average 25% lower than the [reference] biologic ASP. The cost sharing isn't usually enough to drive patient behavior, but we think that eliminating it would help both on the patient and physician side. That bill is called the Access Act. Again, it has bipartisan support in the House, and the Senate version [does as well].

So, those are 2. There are others. There's one around the Purple Book called the Biologic Patent Transparency Act, which Senator Susan Collins [R-ME] initiated. It requires patents to be listed in the Purple Book, which is an FDA document that assists biosimilar developers in trying to assess what patent hurdles they need to overcome to get a biosimilar on the market. Right now, patent thickets, where a [reference] biologic manufacturer tries to extend monopolies by obtaining additional patents around the product, are a big problem for biosimilar competition. Listing patents in the Purple Book would help a biosimilar developer more readily identify the patents that need to be addressed.

There are others around shared savings, which would really provide an opportunity in Medicare Part B for patients and providers to share in the savings that Medicare already recognizes every time a biosimilar is used. And this would be a demonstration project that the CMS Innovation Center could launch to test out the shared savings model, which is another incentive to increase biosimilar uptake. So, those are just a few.

CfB: How do you size up the prospects for approval of these bills?

Well, of course, we all know the current environment is very focused, obviously, on the pandemic response and related matters. So, drug pricing legislation had to take a backseat. But the administration has publicly continued to say it's a priority. There is full broad bipartisan and bicameral support for increases in physician reimbursement, for example, so, that's probably the one that's most likely to pass.

CfB: To build off that, how do you see the current election affecting progress for biosimilars?

Biosimilars are a really important part of reducing prescription drug costs for Americans and that continues to be, [especially] before the pandemic, the number 1 issue that voters cited as an area of concern. It's always in the top 5 or so. So, certainly the concern and public appetite for solutions to the high cost of prescription drugs isn't going away anytime soon. And no matter who ends up in the White House, it's clear that policymakers need to come together to enact policies that will address that. Biosimilars are a large part of that solution and a really important tool in the toolkit around the issue. So, we think that whatever the election outcome may be, biosimilars will continue to be a big issue.

CfB: The Supreme Court's review of the individual mandate puts the Biologics Price Competition and Innovation Act (BPCIA) in jeopardy. Can you explain the issue of severability and the AAM's position on this important case?

So, you're absolutely right. Once again, the Supreme Court is tasked with reviewing a challenge to the Affordable Care Act, also known as Obamacare. And that challenge, like many prior challenges, centers around the constitutionality of the individual mandate of being required to have insurance or pay a penalty. The Affordable Care Act was a large piece of legislation, and it includes the BPCIA, which is the legal pathway that allowed the FDA to review and approve biosimilars.

So, the BPCIA is caught up in this. It was really a piece of legislation that can stand on its own 2 feet, but in order to pass, it was attached to the Affordable Care Act. [This sort of occurrence happens often with] different legislative measures. Because of that, we feel strongly that we can make the case that [the BPCIA] can be severed from the rest of the law, because it [can] stand by itself.

So, AAM and the council filed an amicus brief with the court arguing that because the plaintiffs in the case would not have standing to challenge the BPCIA itself and they would benefit from the savings and public health benefit that the biosimilars pathway provides, that it can be severed. There was a big legislative process around getting the BPCIA drafted, finalized, put into the Affordable Care Act and [getting it to have] bipartisan support. It was written as a free-standing bill, and it would have stood on its own as a legislative document had it not been rolled in. So, it would not be affected by the outcome of the of the actual issue that's being adjudicated by the court [had it not been] included. So, we do think it's severable and that's the argument we made in our amicus brief.

CfB: Based on your experience, what do you expect may result from the court proceedings?

Well, it's hard to speculate on what the outcome of litigation will be. Certainly, there is a lot of evidence that we provide in our amicus brief on the need for the BPCIA, the savings it brings to biosimilars, the public health benefit, etc. We have seen many stakeholders such as patient and consumer groups, be very supportive of biosimilars in all kinds of contacts and I think that many of them are looking for ways to engage on this case.

So, I think it will be tied up in the court for a bit of time. The decision and the oral arguments aren't expected until the fall, which means a decision would happen after the election, probably in early summer. And if the Affordable Care Act falls to this challenge, then the BPCIA would need to be reauthorized by Congress as a standalone piece of legislation. I don't think [that] is any anyone's desired outcome, because every time you revisit a piece of legislation, there are always opportunities for interested parties to try and leverage that and ask for more or ask for things that weren't clear to be taken away. So, it's a bit of a challenge and we're very hopeful that it will be severed.

CfB: To learn more, visit our website at centerforbiosimilars.com. I'm Matthew Gavidia, thanks for joining us.

Christine Simmon, executive director of the Biosimilars Council and senior vice president of policy and strategic alliances at the Association for Accessible Medicines (AAM) discusses potential legislation that the AAM is advocating for and how the upcoming election and Supreme Court decision will affect biosimilars.
 

Part 1: Christine Simmon Discusses the Individual Mandate and Biosimilars

Here are the top 5 biosimilars articles for the week of June 8, 2020.

5. Downward “drift” in batches of reference trastuzumab shed more light on the importance of antibody-dependent cell-mediated cytotoxicity on survival, 

 at ASCO20 Virtual, the annual meeting of the American Society of Clinical Oncology.

4. The COVID-19 pandemic put a crimp in the FDA’s new drug and biosimilars review activities. In so doing, the pandemic helped make the case for an 

 to upgrade its system for assessing its resource needs for biosimilar application reviews.

 that the European Commission has approved their etanercept biosimilar, Nepexto, for all indications of the reference product.

 will enable Amgen to bring its biosimilar for eculizumab to market in 2025, giving originator company Alexion breathing space to bolster its revenue base by developing sales of a follow-on product.

1. As part of pilot program designed to improve access to cheaper medications in oncology, a rituximab biosimilar from Celltrion has 

 for use by the World Health Organization (WHO).

To read all of these articles and more, visit 

The Top 5 Biosimilars Articles for the Week of June 8

The Center for Biosimilars® (CfB): Hello I'm Matthew Gavidia. Today on the MJH Life Sciences News Network, The Center for Biosimilars® is pleased to welcome Dr Joseph P. Fuhr Jr, professor emeritus of economics at Widener University in Chester, Pennsylvania, who is an expert on antitrust health economics and pharmacoeconomics issues. 

To get started, Joe, can you discuss why it is important to have a robust biosimilar market in the United States? 

Yes, it's important to have biosimilar competition in the United States because competition decreases price and increases access. It gives the originator the incentive to replace the product now facing competition with new products to increase the company's revenue stream. Also, it frees up money to pay for those new products.

CfB: Can you tell us about the high cost of bringing a biosimilar to market and what that signifies?

Yes, it is estimated to cost between $100 to $200 million in around 5 to 6 years to develop a biosimilar. Amgen spends around $200 million to develop a biosimilar. It takes about $1 to $5 million and about 3 to 5 years to develop a generic. Thus, biosimilar firms must generate considerably more revenue to get a return on investment.

What other barriers are there for bringing biosimilar to market?

Besides the high costs of research and development, [there is] FDA approval, including for manufacturing site acceptability; originators' response litigation, especially involving patents; stakeholder education; required postmarketing [pharmacovigilance]; the lack of automatic substitution at the pharmacy level; and biobetter development, which is the second generation of the originator product.

What type of companies are ideally suited for biosimilar development?

Established biopharmaceutical firms that have already developed biologics are ideally suited because they have already had the experience and expertise in developing biologics.

There have been many biosimilar developers so far, but not all of them are sticking around. Why is that?

The most compelling reason is that they believe they cannot get a return on investment. Some are leaving due to lack of expertise and others are leaving because of considerable competition in particular markets.

Will market dynamics give us the right number of biosimilars and the right number of companies? How well is the market functioning right now?

In any developing market, there are firms that will succeed and others that will fail. It's just the way a new market develops. Eventually the market will be in equilibrium with the right number of firms. The US market is presently not functioning very well. But it took many years for the generic market to develop.

We have as many as 5 approved adalimumab biosimilars lined up for 2023 and many more in the works. Is this a good situation for consumers or for the biosimilar companies themselves?

It would have been better if the biosimilars could have entered earlier, since that would have brought prices down sooner. It will be interesting to see how low prices will go in 2023 and how many more firms will enter [the market]. More firms entering will be good for consumers, but bad for biosimilar companies, because more entry will lead to lower prices. With the dynamics of the market, we'll see some firms eventually leaving the market.

For companies losing revenue from blockbuster drugs going off patent, do you see biosimilars as offering significant replacement revenue?

Some originator companies have decided not to enter the biosimilar market and [instead] concentrate on making up loss revenues through new products. Others are looking for a combination of new products and biosimilars.

Are we seeing sufficient discounts now from biosimilars or is it too early?

It depends on how you define significant. One would not expect prices in the US biosimilar market to fall percentagewise as much as they have in the generic market. However, even though the percentage may be lower, the actual decrease would be much greater because of the considerably higher price of biologics. A 90% decrease in the price of a $100 drug results in a $90 savings, whereas a 40% decrease in a $220,000 biologic will result in an $88,000 savings.

There are now 5 trastuzumab biosimilars on the market. What sort of pricing effects do you anticipate here?

Generally, the more competitors, the greater the discounts. So, we should see considerable discounts in this market.

What are the dynamics of very rapid and steep discounts caused by biosimilars, such as those that have been noted in Europe, and how might this affect the level of competition among biosimilar companies?

The deep discounts in Europe have helped consumers and the countries paying for them considerably in the short run. However, such deep discounts will make it more difficult for biosimilar firms to get a return on investment, and that's leading to fewer firms entering the market and possibly lower price discounts in the long run.

What will a mature biosimilar market look like? [Will it look] something like they have in Europe?

Probably not. For the most part, Europe is a single-payer system, whereas, in the United States, we have multiple payers. So, one would expect a different market as a result of the multiple payers.

Do you see biosimilar competition ultimately bringing down the cost of specialty medicines significantly for the American health care consumer?

The market will eventually evolve, which should lead to more competition and considerable savings. If the market does not evolve, the United States will see price controls, which will lead to less innovation. This will adversely affect consumers because fewer drugs that [are lifesaving] or increase quality of life will be developed. Biosimilars are a grand experiment. If competition doesn't work in this market, that is where the government will get involved and put in price controls.

To learn more, visit our website at centerforbiosimilars.com, I'm Matthew Gavidia. Thanks for joining us.

Joseph P. Fuhr Jr, PhD, professor emeritus of economics at Widener University in Chester, Pennsylvania, and an expert on antitrust health economics and pharmacoeconomics discusses how future biosimilar competition will affect consumers and market development.

Joseph Fuhr, PhD, Discusses Competition for the Growing Biosimilar Market

Here are the top 5 biosimilars articles for the week of June 1, 2020.

Number 5: Cancer drug prices are rising in the United States and Europe, but European regulators negotiate drug prices, and the results are seen in pricing trends, 

 for ASCO20 Virtual, the annual meeting of the American Society of Clinical Oncology.

Number 4: Abstracts presented at ASCO20 Virtual 

 on physician prescribing of biosimilars and cost savings in the oncology space.

Number 3: The rituximab biosimilar candidate ABP 798 met primary and secondary end points for safety, efficacy, and immunogenicity 

 via a Securities and Exchange Commission filing, Alexion said it had settled with Amgen over eculizumab patent disputes, allowing Amgen to bring a competing biosimilar to market in 2025.

Number 1: A study presented at ASCO20 Virtual 

of biosimilar pegfilgrastim to lower costs in the Oncology Care Model (OCM), where pegfilgrastim expense amounts to 5.3% of the total cost of cancer care.

The Top 5 Biosimilars Articles for the Week of June 1

Hello Matthew Gavidia. Today on the MJH Life Sciences News Network, The Center for Biosimilars® is pleased to welcome Ha Kung Wong, intellectual property law attorney with Venable Fitzpatrick in New York and April Breyer Menon, expert on biosimilar patent law and the founder of April Breyer Consulting in Chicago.

To get started, April, can you discuss what were the circumstances that prompted legislators to offer the Hatch-Waxman Integrity Act?

So, the Hatch-Waxman Integrity Act deals with the interplay between generic and biosimilar FDA approval pathways and their patent dispute frameworks. Currently, a company seeking to bring a generic or biosimilar drug to market can take advantage of a shortened FDA approval pathway that allows them to rely on some of the data from the reference product's application for generic drugs. That's called the Abbreviated New Drug Application (ANDA) pathway and for biosimilars, that is the pathway that set up under the Biologics Price Competition and Innovation Act or the BPCIA.

Patent disputes are guided by frameworks that were set out by Congress. So, for generic drugs, we have the Hatch-Waxman framework, and that has patent listings in the Orange Book for the small molecule drug patents and then it deals with certification letters on which patents may be challenged in litigation and sets up a 30-month stay for the litigation to take place. For the BPCIA, that sets up the patent dance information exchange between the [reference] biologic manufacturer and the biosimilar [manufacturer].

Starting in 2012, additional patent dispute procedures were introduced, called inter partes review (IPR) and post grant review (PGR) proceedings, at the patent office. These are possibly a faster way to challenge drug patents than in the district court. So, there was some concern after the IPRs and PGRs started that they were upsetting the balance that Congress have set out in the patent frameworks in Hatch-Waxman and BPCIA. So, the Hatch-Waxman Integrity Act actually seeks to restore that balance by requiring manufacturers to either choose to use the shortened FDA approval pathways or use an IPR PGR proceeding. Basically, they can't use both and the idea is that was kind of reset the balance that Congress intended.

This bill has been stymied in Congress for 15 months. What are its chances of passage and why?

So, this bill has actually been introduced in the Congress 3 different times. The fact that it's been stalled for so long could be concerning for passage, especially since right now it really seems that Congress and the current administration seem to prefer legislation that would decrease drug prices and bring generics and biosimilars to market more quickly.

And it's possible but this bill could actually adversely impact that effort by prolonging time disputes and slowing down the approval of generics and biosimilars. An example of that would be, now, a biosimilar manufacturer could file an IPR early on in the product development process and it could potentially have that IPR invalidate the patent before litigation would even be filed. So, it could completely eliminate the need for litigation on that patent.

Another challenge of this bill is that it's singling out 1 particular industry, and it's effectively removing some of the mechanisms that they have to challenge patent validity. This bill may effectively end up shielding small molecule drug patents and biologic drug patents from IPRs completely, just because of the fact that FDA approval is so expensive. The shortened drug pathway for approval would be preferable probably to using an IPR or PGR. Overall, I think that there are a lot of challenges that might come into play to get this bill passed, and especially the sentiment in Congress regarding drug prices and wanting to bring biosimilars and generic drugs to market more quickly.

So, whether or not this bill goes anywhere, what would you say are some of its most logical or meaningful elements?

I think that the biggest impact of this bill is that it would potentially eliminate duplicative proceedings. So, right now, the drug patents could be challenged both at the patent office and in the district court. And I know I gave an example earlier of how that could speed up the process if the IPR was filed before litigation, but the potential concern is that IPRs could actually drag out litigation. If the litigation is filed first, and then an IPR is filed, then the litigation might be stayed while the IPR is decided, and then they have to go back to the litigation. So, it can actually cause the disputes to take longer and be more expensive.

Another concern is that there are different standards at the patent office and in district court. So, you could actually end up having a different patentability determination for the same patent. A couple of examples of the different standards would be that there's no presumption of validity at the patent office. The patent office uses the preponderance of the evidence standard, which is a reduced standard compared to litigation and the district court.

Data have actually shown that duplicative proceedings have been a pretty big issue since the creation of IPRs and PGRs. Pentaxia did a study of IPRs from when they started in 2012 through the first half of 2017 and they found that almost 80% of IPRs were filed in what they called a defensive proceeding. So, that meant they were filed after the district court case had already been filed. Those are the ones that tend to drag out the patent litigation longer.

We've actually collected some data for Biologics HQ looking at just biologic drug patents, and we found that for those [kinds of patents], only 37% of IPRs are actually filed patents that were already in active district court cases and that would be a district court case between any parties. So, if you look at only IPRs filed on patents that have been challenged by the same parties, it was actually only 26%.

So, this doesn't seem to be quite as big as an issue for biologic drug patents as [it is for] patents as a whole. We did a little bit different analysis for small molecule drug patents listed in the Orange Book. For that we looked at whether patents have been challenged by both and IPR and in the district court litigation at any time by any party, and we found that actually 95% of those patents were challenged in both. If you do that same analysis for biologic drug patents, it's 64%. So, you can see that duplicative proceedings at some time or another are an issue. This bill could actually be somewhat helpful to eliminate those, although it might have a bigger impact on small molecule drugs than biologics.

CfB: Moving on to the Stop Stalling Act. This act is intended to prevent the abuse of citizen petitions by innovator drug companies. First of all, what is a citizen petition and how have these been misused? And additionally, April, can you discuss how widespread is this practice?

Sure. So, citizen petitions are a way for the public to raise scientific and health concerns about drugs that the FDA is reviewing. These petitions can either ask that the FDA take some sort of action or refrain from taking action on a particular drug application. The citizen petition process can be misused by people or companies that are filing petitions that don't actually raise a legitimate scientific or health concern and they only seek to delay FDA action by causing unnecessary investing. Sometimes they even file a series of sham petitions, just to delay FDA approval for as long as possible.

This type of petition does appear to be used in a rather widespread manner. In 2016, Rutgers Law School did a study where they looked at a particular type of citizen petition that would request the FDA take action against a pending generic drug application. And they found in the 4 years before this study that 92% of that type of citizen petition were filed by brand name pharma companies, and then 92% of those were ultimately rejected by the FDA. So, that shows that there wasn't an actionable issue in 92% of those petitions that were being filed.

This act would make sham petitions actionable in what way?

Well, this act creates a Federal Trade Commission (FTC) cause of action against sham petitions as unfair methods of competition. So, the act would define a sham petition as a petition or series of petitions that are objectively baseless and attempt to use a governmental process to interfere with the business of a competitor. It seems to be trying to narrowly tailor it to just this type of sham petition and not any petition, only those that are objectively baseless.

It's also going to create a rebuttable presumption of illegality for petitions that the Secretary of Health and Human Services [HHS] determines were submitted primarily for the purpose of delaying approval of the drug application. And then, this act would grant the FTC the authority to seek a civil penalty in district court for any violations of the act.

No, it hasn't. The FDA guidance is separate from the act because the act creates a cause of action for the FTC to bring a case in district court and to seek monetary penalties. The FDA guidance, on the other hand relates to how the FDA will actually handle the citizen petition. So, it describes how the FDA will determine whether it will delay a drug application's approval, because it's actually necessary to protect the public health, or whether the FDA can just summarily deny the petition because on its face. It doesn't raise a valid scientific or regulatory issue. So, really, the guidance and the act would work hand in hand, with the FDA having the ability to summarily deny the petition is a sham and then the FTC would then be able to go to district court and seek penalties for filing that petition.

How likely is it for this legislation to pass?

This legislation appears to have bipartisan support. It's already advanced in both houses of Congress and we can see from the FDA guidance that the FDA is aware of this issue and is taking it up and tried to make strides towards preventing this. So, it really seems that for this particular legislation that there are very few challenges at the moment.

The Biologic Patent Transparency Act would force innovator companies to make public the patents protecting their products and is intended to limit the filing of patents to block ongoing biologic product applications. Ha Kung, why has patent transparency become a problem?

It's kind of like asking, Matt, why didn't the Chicago Bulls re-sign Phil Jackson and Michael Jordan in 1999, giving them 1 more chance to win a seventh championship ring? The answer is there were lots of problems. Same is true here, but I think that there's 1 reason that's particularly relevant. Biologic drugs are very scientifically complex, as most come from living organisms and aren't as simple as small molecule drugs, where everything is essentially just a handful of carbons, oxygen, and hydrogen. There are often many more patents filed on each biologic drug because of this complexity, including composition of matter, formulation, methods of use, and most important, manufacturing patents, something that might not have been as important for the small molecule space. So, some innovator biologic drug manufacturers, because of this, have identified over 100 patents that potentially cover aspects of the drug.

And with all the scientific and manufacturing complexity, it can be difficult for an innovator to determine exactly which patents cover which aspects of the product, which means it can be even more difficult for a biosimilar manufacturer to identify all of the potential patents that may cover its biosimilar product.

So, as a result of this, biosimilar manufacturers may not have a complete understanding of what patent issues they may face in the future prior to committing resources to development. And this is a very, very different scenario than for the generic small molecule drug manufacturer that has much more patent transparency, because they can view the list of patents covering small molecule drugs in the Orange Book. So, as you can see, doing something similar for biologics may reduce issues of patent transparency in the field. So, the Biologic Patent Transparency Act would require innovator companies to list patents for which a holder or exclusive licensee believes a claim of patent infringement could reasonably be asserted by the holder in the FDA’s Purple Book.

So, it ended up being kind of the biologic version of the Orange Book, if you will. However, while the Senators’ [Susan Collins, R-ME; Tim Kaine, D-VA] comments on the bill state that it will target patent thickets by limiting enforcement of patents issued after a biosimilar application has been submitted to the FDA, the actual text of the bill does not include this provision. Thus, the bill currently will not limit the filing of patents that could impact potential biosimilars.

How will the act increase transparency and create advantages for biosimilar manufacturers?

Well, I think there's a couple things to consider. First of all, it adds information to the Purple Book such as biosimilarity, interchangeability designations, exclusivity [periods], approved indications, and it makes the Purple Book searchable. In other words, it actually makes the Purple Book usable and useful, like the Orange Book is. So, I think there's some benefit there. It also specifically requires that in the Purple Book you list compositions, method of use, and method of manufacturing patents. That's something different than what you see in the Orange Book, which the holder or, in some cases the exclusive licensee, believes a claim of patent infringement could reasonably be asserted by the holder, which is similar to the requirement for listing in the Orange Book. They also say that you want to list any patent or patent infringement that could reasonably be asserted.

So, there is some parallel there, and we've seen how useful the Orange Book is. And this could make the Purple Book more useful. Now, of course, there's a penalty for failing [to list the patent in a timely manner]. You can't bring an infringement action under the BPCIA if you don't list a patent, and that's pretty draconian, and that's something we'll talk about in a little bit. But because biosimilar manufacturers would know in advance if they have this listing, which patents they could be infringing, they may be able to challenge patents earlier in the product development process or attempt to design around the patents. This may impact the pace of patent dispute processes and get biosimilars to market more quickly.

Another potential advantage to biosimilar applicants is that they could essentially circumvent the BPCIA patent dance by choosing not to provide the RPS [reference product sponsor] a copy of their [abbreviated Biologics License Application] to start this patent dance process, but they would still have the benefit of knowing which patents could be asserted against them pursuant to this listing in the Purple Book.

Contrary to the way it appears on the surface, this bill is highly complex and perhaps impracticable. Can you explain why?

Well, on the one hand, it's very challenging for a reference product sponsor [RPS] to know which patents to list. So, with a strict penalty for failing to list, the number of patents in play may actually increase, since an RPS may be more likely to list any patent that could possibly be reasonably relevant, which still leads to each litigation being determined on a case by case basis, after evaluating all the applicable patents during the patent dance. Ultimately, this may then have little impact on the speed of litigation. Now, on the other hand, there may be minimal incentive for an RPS to list patents, like there is in the Hatch-Waxman Act, because there's no specific accrued benefit, like the promise of 30-month stay of generic small molecule drug approval. So, maybe they would not want to list at all.

This does, as I mentioned earlier, have this penalty of barring infringement claims, and that doesn't exist in the Hatch-Waxman space. And some people may see this as being too harsh of a penalty, so that's another thing that could be an issue. Then, they could be seen as potentially inconsistent with the entire process of the BPCIA. I mean, Congress did go through and put together a pretty elaborate scheme for trading patent information and the BPCIA would absolutely be shortcutted, in a process that was not contemplated at all by the BPCIA or Congress when they passed it.

And then, all together, this could lead to further disincentivizing the use of the patent dance by a biosimilar because why would they need it anymore? They have to list the patents and the Purple Book. At the end of the day, this doesn't mean you have to actually limit the number of patents that an RPS could obtain on a biologic. So, it's really unclear how this would address the so-called patent thickets.

Given all that, is there a way to make this bill workable and gain more transparency?

Well, that's akin to asking whether there's anything we could do to make the last Star Wars movie more watchable. The answer is probably not. But that's an interesting question here because there are interesting aspects in the bill's current form worth saving, such as improving information in the Purple Book like biosimilarity, interchangeability designations, exclusivity, and improved indications, all of which make the Purple Book more beneficial to everyone.

Now, perhaps 1 potential change could be to provide an explicit incentive for listing the patents in the Purple Book, and making the penalty for failing to list a patent less severe, similar to what we see in Hatch-Waxman, where there's a 30-month stay of approval given for patents listed in the Orange Book. And the penalty there for failing to list patents is simply you don't have the 30-month stay approval, and not the complete removal of your ability to enforce the patent. So, perhaps that way, it becomes more of a give and take, like the Orange Book space, and it might be more palatable on both sides and plus more practical in terms of effects.

CfB: The Affordable and Safe Prescription Drug Importation Act would allow the United States to import select lower priced drugs from Canada, possibly leading to drug imports from other countries. American people are strongly in favor of this type of legislation, but there are some very real problems with this bill. Can you explain this, Ha Kung?

Yeah. I'll do this in summary fashion because there are a lot of problems here. First of all and foremost, there may be quality and safety concerns about allowing people to take drugs that haven't been approved by the FDA. We all know the story of thalidomide in the 1950s and how it was approved overseas. It led to tragic birth defects and it was never approved by the FDA. Clearly, we have the FDA for a reason and bypassing requirements can be very dangerous.

And secondly, drug availability may be an issue. I mean, the fact of the matter is that if only 20% of US prescriptions were to be sourced from Canada, we would exhaust the entire Canadian drug supply in 103 days, which I don't think Canadians would be happy about. And of course, that's reflected in what Canadian officials have said. They've generally been opposed to this policy for that very reason. And ultimately, it may not be an efficient way to lower drug prices, as compared to simply implementing pricing restrictions, similar to those that were implemented in Canada.

And finally, we have actually had similar policies that were introduced in 2003 and 2017. Neither passed. It's unclear why this would be any different.

Given all that, how would you rate this bill's chances of passage?

Well, I'd say this bill's chances of passage are about as high as the chance that Carol Baskin from the Netflix documentary, The Tiger King, wasn't involved with her ex-husband's disappearance. She was super shady, but I digress. While this bill appears to have significant public support, the logistics may not be feasible. Canada doesn't have the drug supply necessary to supply the United States, and if only a fraction of the drugs are imported from Canada, the savings are going to be minimal. And of course, with the potential safety concerns with bypassing the FDA, I’d say it would be challenging for this bill to pass.

CfB: The Biosim Act will temporarily increase reimbursement for biosimilar drugs to average sales price (ASP) plus 8%, up from the current 6% plus ASP. So, April, what's the idea behind paying physicians more for using biosimilars?

 The idea is that financial encouragement may help to increase the uptake of biosimilars, which we know has been an issue so far in the United States. So, currently biosimilars and reference products are reimbursed at the same rate. That means that each 1 is reimbursed at their ASP, and then 6% of the reference products’ ASP is added to that. So, from a reimbursement perspective, there's really no incentive to prescribe one drug over the other.

Now, there might actually be increased costs to the doctor in prescribing a biosimilar. Some examples would be that they may have to spend extra time with the patient explaining what biosimilars are and answering their questions. If they're switching from a reference product to a biosimilar, they'd have to explain the risks and benefits of that. They might have to spend extra time monitoring and following up with the patient. And all of that together could make prescribing the biosimilar a less attractive alternative. So, the idea is that this added reimbursement for biosimilars might help doctors offset those potential increased costs.

How would you rate this bill's chances of passage as currently packaged?

 Well, so right now, this bill is packaged as an amendment to the Lower Drug Costs Now Act, which is a very expensive drug pricing bill that came out of the House. And because of the way it's packaged, it might have a difficult time passing just because of some of those other provisions in that act. One example is that another provision allows the government to negotiate drug prices paid by Medicare. And that provision in particular has been opposed by a number of people in Congress, particularly Republicans, because they feel it interferes with the free market. So, even if this drug itself might not have so many issues because of its past packaging, it may make it rather difficult to pass.

So, Ha Kung, in an election year, how might this dynamic spur or hinder the passage of drug price legislation?

Well, we all know that the Trump administration can be unpredictable, not only on Twitter, but in terms of policy. It seems like drug pricing is something that was a priority. So, President Trump may push for legislation, but it's unclear at this point, since there's so many other priorities in the immediate horizon, not the least of which is [coronavirus disease 2019] COVID-19 and the economy.

Regardless, the public is generally in favor of drug pricing initiatives. So, we may see legislators trying to push something through or at least provide some demonstrable progress as part of their bid for re-election or in support of their party. However, let's not forget the lobbyists, as many companies and groups that contribute to campaigns appear to oppose many of these bills, which may lead to limited congressional support.

Not to forget about the COVID-19 pandemic, how does this play into the success or failure of the legislation we've discussed?

Well, with all the attention currently focused on COVID-19, Congress has had limited ability to be in session and debate these bills. So, clearly, that makes it difficult for these bills to progress. But COVID-19 could have a long-term impact on people's health care. So, it will be interesting to see where some of this legislation could go, as health concerns are at the forefront of everyone's mind, including politicians’. Clearly, access to medications is in part based on [intellectual property] and regulatory requirements, and COVID-19 is a clear example of a virus unchecked by any developed treatment. The current increased focus on finding better medications for future potential pandemics may spur increased interest in passing bills that impact future biologic drug uptake, particularly with respect to vaccines.

Even if legislation can speed approval of biosimilars, we still have issues with uptake. Can you explain?

Well, while the uptake has been increasing the biosimilar market share still significantly lags behind reference products for most drugs. Even if more drugs are approved, the United States still needs to make efforts to increase awareness and education on biosimilars for doctors and patients. Biologic and biosimilar drug prices may also require more significant control by the government to encourage use of those drugs by doctors, who are less familiar with them and also subject to taking up more of their time to administer them since they may need to spend more time educating patients on biosimilars, answering questions, and in turn, have increased follow-up appointments. So, ultimately, you need to get buy-in from the politicians, the payers, the physicians, and the patients, and all that is a very tall order.

To learn more, visit our website at centerforbiosimilars.com. I'm Matthew Gavidia. Thanks for joining us.

An extended interview with Ha Kung Wong, JD, an intellectual property law attorney and partner at Venable Fitzpatrick in New York and April Breyer Menon, JD, an expert on biosimilar patent law and founder of April Breyer Consulting in Chicago discussing potential biosimilars legislation.

Ha Kung Wong and April Breyer Menon Discuss Promising and Not-so-Promising Biosimilar Legislation

The American Society of Clinical Oncology held its annual meeting, ASCO20 Virtual, from May 29 through May 31. The meeting was conducted on a digital platform because of the coronavirus disease 2019 (COVID-19) pandemic and featured a number of study findings and presentations on the importance and potential impact of oncology biosimilars.

 of biosimilar pegfilgrastim to lower costs in the Oncology Care Model (OCM), where pegfilgrastim expense amounts to 5.3% of the total cost of cancer care.

 to support its bid to market a trastuzumab biosimilar candidate (HD201, Tuznue), based on findings presented at ASCO20 Virtual.

A study presented during the conference revealed that 

 to prescribe biosimilars if there is potential for their practices to lose money or control over the preferred medication.

Another study showed very high recognition and knowledge of biosimilars among oncologists in Brazil, where biosimilars could make a difference, and 

The idea that “resources affect who lives and dies” is cringeworthy, but this is a very real phenomenon that reveals itself in multiple ways throughout the US cancer treatment system, 

, who reviewed the evidence presented at ASCO20 Virtual, and concluded that some deep reforms are needed in oncology care to improve access.

Cancer drug prices are rising in the United States and Europe, however European regulators allow for negotiating of drug prices unlike the US, and the 

, investigators said in a conference presentation.

A study revealed that the rituximab biosimilar candidate ABP 798 

 for safety, efficacy, and immunogenicity and was similar to that of the reference product (Rituxan in the United States and MabThera in the European Union).

, biosimilar filgrastim (Zarxio) was found to be cost-effective when used to treat patients with nonmetastatic non—small cell lung cancer (NSCLC), according to a study presented at the conference.  

 with cancer from reference pegfilgrastim (Neulasta) to biosimilar pegfilgrastim (Udenyca) not only reduces the cost of prophylaxis treatment for chemotherapy-induced febrile neutropenia (FN) but also provides funds for adjuvant treatment.

 of patients with breast cancer who received febrile neutropenia prophylaxis with biosimilar pegfilgrastim (Udenyca) or reference pegfilgrastim (Neulasta) has not only demonstrated comparable efficacy between the 2 products but also shown that large-scale comparisons of this nature can be done.

To read all of these articles and more visit 

Here is a summary of our coverage from ASCO20 Virtual, the annual meeting for the American Society of Clinical Oncology (ASCO).

ASCO20 Virtual Biosimilars Roundup

That may be a good place to finish because it is complicated, and over the course of the conversation today we’ve introduced that complexity at so many different levels.

There is a lot for viewers to take from this.

Again, this was great. It was informative. I had a lot of fun. When you can both inform and, to some degree, entertain, especially since we’re doing everything virtually these days, you can’t ask for more than that.

My thanks to all of you for this rich and informative discussion. Before we conclude, I want to go around the horn and get a 30-second final thought on the future of biosimilars. We’ll go in reverse order, so we’ll start with Karina and then Kathy, Michael, and Bhavesh. Karina, you’re on.

Thank you, Bruce. Just to echo what everyone else has said, I think that strategically, we are looking at a 1- to 3-year plan to disrupt the market a bit, make room, and make decisions that do look at overall cost of care in a long-term method.

I encourage everyone. We believe in the science and the innovation, and we do believe that biosimilars have a place in our long-term strategic plans to help bring down health care costs for the system and the payers, as well as the patients.

We believe biosimilars have the potential to permit us to provide high-value care that is at more affordable to patients and society. That is an invaluable tool that we can add to our arsenal as we try to figure out the best ways to take care of our cancer patients. I’m glad they’re here. They’re here to stay, and we want to do everything we can to encourage their use as appropriate.

What I want to see happen is more real-world evidence published by health systems and providers of their experience with biosimilars. That would really help the adoption rate increase, because that is tied to the cost savings that we want to see to adopt the innovation we have.

One of the biggest challenges that we have not addressed, until this day, is actually having payers control the market. Until that is taken away, we’re still going to have this impedance of adopting biosimilars to the full extent that we need to and that providers want to, so that is going to require some government regulation.

Essentially, we’re not even going to be talking about a biosimilar in a couple of years. We’re going to be using multiple biosimilars 1 week, next week, and next month. This is all going to be obsolete, hopefully.

Thanks, Bhavesh. And thanks to everyone on the panel. Thanks to our viewing audience. We hope you found the Center for Biosimilars® 

® discussion to be useful and informative, and maybe a bit entertaining. I’m Dr Bruce Feinberg. Be well, everyone.

Biosimilars in Oncology: Future Directions

 It sounds as if the value is high for biosimilars. You all have a good long-term strategy and believe they are critical for that long-term strategy. Kathy, you’ve said that even a 5% difference could be meaningful. When we talked about what biosimilars have to do to gain market adoption and make an impact 2 or 3 years ago, there was this notion that it had to be 30%.

We talked earlier about limitations, and yet I’m hearing as little as 5% could be significant. All that sounds like it’s really strong.

One of the things I forgot to mention is that, as you see multiple biosimilars coming onto the market, the wholesale acquisition cost with the list price of the reference product actually stops increasing. Then the ASP [average selling price] starts going down. That’s 1 of the things we don’t actually think about. We’re lowering the cost. If we didn’t have the biosimilars, the cost of the reference product would continue to go up and the ASP would also continue to go up.

 Let me challenge you with the counterpoint. As a result of what we’re saying today and the compelling case you’re making for biosimilars, a company that has significantly impacted biosimilars, Genentech Inc, decides they’re going to go to parity with the best of the current biosimilar contracts for each of their brands. Do you go back to the established brand that has all the evidence?

Yes, if they’re going to lower their price to the level of the biosimilars or even lower, if it’s more competitive, then of course.

All right. Anyone else want to weigh in? If it’s strictly a price story, then the question is, how close a price parity?

These companies have enjoyed exclusivity for such a long time, right? It’s not fair that the health care system, the patients and the insurance companies actually pay for the increase in price. For a Genentech drug that you talked about, when they actually increased the price of that drug in 2 years, it resulted in almost a $1 billion increase to the health care system. That would have never been resolved if we didn’t have a biosimilar coming through. They would have to come down to the level.

We have had that conversation, and the answer within our organization is that certain originator companies had their chance to be good partners. Some chose to; some chose not to. To your point, we will not be going back to certain originator manufacturers because we’re looking at that much larger picture, even with a parity contract. We believe in the science and the innovation behind the whole biosimilar market.

, and this is making the nightly news. Thank you, Kathy. We just did that. That was great. I think it’s realistic, and the candor is so important for the audience to understand that this is a complex issue.

I’d like to add the point that we made earlier about infliximab versus oncology biosimilars. What happened in the infliximab space was that the originator product came out, dropped its price really low, and dangled that in front of a lot of payers and health systems. Some did choose to take that early on, saying, “Let me get this cost savings right away in year 1,” and some chose to wait it out. I do think it’s a bit of both, and it depends on the financial situation of the decision maker at that point in time.

This is a really complicated subject. We always look at it from this perspective: how can we add the most value to the patient and the health care process? We’re seeing examples where, because of the larger rebates the originator product can provide—even though it’s a more expensive product for the patient&mdash;or the provider’s hands being tied, they have to give the originator product. That’s where it gets complicated so quickly. Each situation is not only unique but complicated.

Competition in the Biosimilar Marketplace

 It’s interesting that I’m hearing a lot of long-term strategy. Bhavesh, you went long term and big picture. Michael, for the most part, you went long term in your big picture because it’s a value-based care strategy and not about this year’s numbers. Kathy, you went long, and Karina went long.

I wonder how many community practices with 3 or 5 doctors can afford to think long term. Are they thinking in the business next year? I wonder about that thought process, and they are not an insignificant segment of the oncology provider space.

 In terms of what the financial impact has been for us, from our biosimilar experience, by adopting about 98% of our patients, we’re able to save our health system $1.5 million. What does that mean to us and the patients? From a global perspective, 50% of our payments come from a risk-based model. If we’re able to lower that cost, we’re actually able to help sustain our business with our payers longer and also offset the cost of more innovative therapies.

It helps to continue to adopt new therapies and continue the path you need to have in oncology. As you said, it’s long term. You’re not going to see an immediate effect at the time of your switching.

Something that’s really quirky with list pricing is that you see a lot of contracts that are not publicized, which are not reflective of what you see in a list price. You might be seeing a list price as 10% or 15%, but there are institutions that are getting 30% or 40%, which is really helping to drive that cost down. Based on Kaiser Permanente, they publicize that they’re going to be saving $200 million from switching to oncology biosimilars. That’s a huge impact for a single payer, so there is a long-term benefit that we’re going to see.

 You bring up a very good point, Bruce. Many practices are used to looking at things from a day-to-day perspective. Do I have the ability to keep my practice open month to month? Overall, the best way to plan long-term survival is to be able to create an environment in which you can change from that philosophy to a longer-term philosophy, which will allow you to keep your doors open.

That’s where we’re working with the smaller practices, so they have the ability to play these long-term games and remain economically viable. That’s happening on all levels. Our institutions are helping with that. I know that some of the payers are investigating and encouraging these types of relationships. We have to constantly evolve in order to continue to meet needs and stay in business, so to speak.