Articles

The United States has missed out on almost $20 billion in savings as a result of not having a competitive biosimilar market, according to findings from the Pacific Research Institute.

Report: Lack of Biosimilar Competition Contributed to Billions in Lost Savings

Breast cancer specialist Hope S. Rugo, MD, FASCO, an advisory board member for The Center for Biosimilars®, has been at the forefront of groundbreaking oncology advancements. 

Rugo Wins Prestigious Giants of Cancer Care® Award

Lotus and CKD Pharmaceutical intend to be among the first to bring a darbepoetin alpha biosimilar to Southeast Asia.

Lotus Inks Deal With CKD to Distribute Darbepoetin Alpha Biosimilar

We sat down with Representative Glenn Grothman (R-Wisconsin), the author of HR 8190, a bill that would waive interchangeability requirements for biosimilar insulins, to discuss why this bill is needed for Americans and what it could mean for future biosimilar legislation.

Not So Different: Rep Grothman on His Bill to Make Biosimilar Insulins Interchangeable

Isha Bangia, PharmD, MBA, is a manager of US market access at Certara Evidence & Access. She received her PharmD from Rutgers University and an MBA from Johns Hopkins University. Her current responsibilities include optimizing product value stories and working with customers to improve access across the US healthcare system. Her experience includes practicing pharmacy, payer market research, and pharma strategy and analytics. Her work has covered many therapeutic areas, including biosimilars, oncology, diabetes, vaccines, and rare diseases.

Amgen's Onpro autoinjector device for pegfilgrastim is a stunning example of how product differentiation via drug delivery devices can protect market share in the biologics market.

Contributor: Drug Delivery Devices Help Originator Companies Retain Market Share

The Center for Biosimilars® (CfB): Hello, I'm Matthew Gavidia. Today on the MJH Life Sciences Medical World News, The Center for Biosimilars® is pleased to welcome Wayne Winegarden, PhD, a senior fellow in business and economics at the Pacific Research Institute (PRI), as well as director of PRI's Center for Medical Economics and Innovation. Can you just introduce yourself and tell us a little bit about your work?

 Oh, absolutely. Good morning or good afternoon, everyone. My name is Wayne Winegarden. As Matthew just said, I'm a senior fellow and director for Center for Medical Economics and Innovation at the Pacific Research Institute. Part of what we try to pursue at PRI, with respect to our health care research, is discuss how free market reforms can improve both the quality of care as well as reduce the cost of care. So, basically, we want to get that productivity that we see in other parts of the economy working in the health care sector. And at the Center, one of the things we focus on particularly is pharmaceutical products and medical devices. Right now, there's a lot of attention and there's specific issues, like [those that concern] biosimilars, that are unique to the pharmaceutical market and that's what we tried to emphasize when we're doing our research at the Center.

To start us off, specialty drug prices continue to climb but has there been a slowdown in the rate of that climb and what might be causing this?

 Yes, especially in the spend. And a lot of that is that we're beginning to see biosimilar competition stand up. For a while we were having a very difficult time getting that foothold in the market. We're still not anywhere close to where we could be or should be. But we are beginning to see the biosimilar market stand out, and that's beginning to have an impact, and over time, hopefully, we'll see more of that.

What are your thoughts on the constant price increases of drugs like Lantus [insulin glargine]?

 For drugs like Lantus, or really, across the market, we're seeing prices rise when you don't have effective competition. But we need to be careful when we talk about prices rising, because the market is so complex. 

Often when we're looking at prices, what we're looking at is the wholesale acquisition costs, or the gross price, which isn't the price systemically. It is the price that the patients' costs are based on, and that's part of the issue with the drug affordability problem that we have, but it's not actually based on the systemic price.

So, there are really 2 things that we need to look at: One is why that price is going up because, especially in specialty drugs, prices are rising too quickly. But also, we need to be very careful when we talk about prices. Here, we're talking about the relevant market price, and often when we talk about drugs that's not what we're talking about.

What's your take on the strength of the biosimilar market in the United States? Are there examples of success and are we poised for greater uptake?

 Yes, and yes. The greatest example of success is Zarxio, which has a majority of the [filgrastim] market. But even the infliximab market, where we've seen the biosimilar competitors drive down the cost of the originator product [Remicade], from a consumer perspective, is a success. Obviously, that raises issues in terms of sustainability of competition, which we need to be very careful about, and we need policies that support long-term durable competition, which is a different issue altogether. 

We are definitely seeing some successes and we certainly are poised for more. I think the education about biosimilars is getting out there. People are recognizing them. And we also have some very important biosimilars in the pipeline that, hopefully, will be in the market soon. And they could make a very, very big difference in terms of the costs.

How about biosimilar uptake during COVID-19 [coronavirus disease 2019]? What do you think we're going to findwhen the dust settles?

 With COVID-19, obviously, the biggest issue in terms of public health in drug is going to be the vaccine. And so that's a little bit outside of the scope in terms of biosimilars. 

Especially because of all the stress that COVID has placed on the health care system, it actually accentuates the need to get [the biosimilar] market up and running and get a much larger [market] share. I mean if generics are 90% of the market for small molecules, we need to get close to that share with the biosimilars to help bring down the cost because of all the stresses COVID has put on [the industry].

Obviously, [COVID has put stress] across the economy, but it has targeted the health care system. And so, [biosimilars] could help promote greater affordability and improve people's health and, especially, adherence because when we have greater adherence, we have greater health outcomes. All of that is amplified because of the current environment that we're in. So, in that sense, it heightens the need for us to get this market up and running faster.

What are your thoughts on the power of large employers to shift their employees toward biosimilars such as Disney and Costco have done, and do you see this trend gaining significant momentum?

 I definitely see it gaining steam. We've seen it in the numbers that we've been tracking the amount of savings we're getting from biosimilars. In the latest numbers that we've run, we're up to $1.8 billion. That was from a few hundred million just a couple of years ago. So, we're seeing much greater usage, greater market share, and the savings are going up. Obviously, the potential is 10 times that, if not more. So, there's a lot more to be gained but we are seeing that [growth] and the power within the large employers. Absolutely. 

If we look at the way the health insurance markets are today, they're driven by the employers. Now, we can have a whole debate about whether that should or shouldn't be the case, but that is the reality today. And so, as large employers switch, you really have that double effect of one; they're moving a large population toward more-affordable drugs—that is a beneficial impact—but [you also have] the secondary impacts of news stories that come from it and the awareness that those drive other large, as well as smaller, payers towards embracing biosimilars. So, that kind of double impact--the good and the excellent and up—is very important. And so, absolutely, we are seeing a positive data trend. It's very meaningful. And hopefully we'll continue to see more of that.

Can you talk about “fail first” or step therapy as a means of getting biosimilars into play?

 Oh, absolutely. Fail first is actually working in reverse when it comes to the biologics market. If we go to the small molecule market, typically, if you fail first when using a generic then, you can get the [reference product]. But basically, you're encouraging the use of the lower-cost product first and then, move to the more expensive product. We have the exact reverse in biologics and that's not the way it should work. It should be that you fail first on the biosimilar and then, you move to the reference biologic. 

But there's also another issue, which is that if you're failing on the originator, the odds of the biosimilar and vice versa, if you fail on the biosimilar, there are a lot of issues regarding the efficacy for that individual patient. I try to stay away from medical issues that are outside of economics and outside of where my expertise is. But you need to also be careful from that angle, where you're not really giving the biosimilar a chance, because if the efficacy is not showing [for the originator], it's not [going to] show [for the biosimilar]. So, you have those concerns as well. One of the most important reforms we need to make to accelerate the use of biosimilars is to address that fail first issue.

Are there any potential strategies for getting payers to steer clear of rebate incentives and put lowest cost biosimilars on formulary?

 There are all sorts of strategies that can be done. One of the things I think is important is to create a separate formulary tier for biosimilars. And you can have certain types of criteria in terms of price discounts relative to originator price or anything you want to have in order to for a product to qualify for it. But in order to share the savings--and that's a big part of the solution is just the savings that the biosimilars offer—the patients, the payer, and practitioners have to benefit. And if we don't get everybody's incentives aligned to have the patient using the biosimilar, then something along that chain isn't going to work well. 

So, you want a separate formulary tier where the biosimilar has lower co-pays, coinsurance, costs to the patient, or you can have higher reimbursement rates for the provider, so they have the incentive to use it. The payer should be saving money. That should be an incentive. You can also give them incentives along the star ratings for Medicare. So, you can give them a boost in the Medicare market. We need to get all of these types of shared savings or shared benefit going so that the systemic benefit, which comes from a lower cost product, is shared by everyone and everyone has the incentive to save that money. They’re all incredibly important reforms that we need and would encourage greater biosimilar use. Obviously, any payer can adopt those changes among themselves, work with their PBM [pharmacy benefit manager] to make and demand those changes. Customers, especially the large customers including payers and employers, need to start demanding better service out of their PBMs to ensure that they're getting the pricing and the value they deserve.

Part 2 of this interview will be available Thursday, September 17

Videos

Wayne Winegarden, PhD, senior fellow in business and economics at the Pacific Research Institute (PRI) and director of PRI’s Center for Medical Economics and Innovation, discussed where the biosimilar market is heading and how employers can incentivize biosimilar utilization.

Part 1: Wayne Winegarden, PhD, on How Employers Can Better Manage Their Formularies

At the European Society for Medical Oncology (ESMO) Virtual Congress 2020 this week, detailed presentations will be 

biosimilar studies for agents from Mylan, Samsung Bioepis, and Shanghai Henlius Biotech.

Investigators plan to report phase 3 efficacy and safety data for Mylan’s proposed bevacizumab biosimilar MYL-14020 versus the reference product, Avastin, in the first-line treatment of patients with stage IV nonsquamous non–small cell lung cancer.

Investigators randomized 671 patients to the biosimilar candidate (n = 337) and Avastin (n = 334). In the preconference abstract, they reported that the confidence intervals for objective response rate (ORR) were within the predefined equivalence margins, demonstrating equivalence for MYL-14020.

 that the FDA had accepted its 351(k) filing application for MYL-14020. An application decision date was scheduled for December 27, 2020.

A poster on a randomized equivalence study for the Shanghai Henlius Biotech trastuzumab biosimilar (HLX02) also will be presented at ESMO. The multicenter study randomized women (N = 649) 1:1 to receive intravenous HLX02 or a European Union–marketed version of reference trastuzumab combined with docetaxel, with the primary end point being ORR at week 24.

In their preconference abstract, the investigators reported a 71.3% ORR for HLX02 vs 71.4% for the reference product. The group difference of 

7.0% to 6.9%) was “completely within the predefined equivalence margins of ±13.5%.”

In June, Henlius and Accord received a positive 

 for marketing approval for HLX02 from the European Medicines Agency.

Samsung Bioepis reported phase 3 exploratory 

 for its bevacizumab biosimilar (Aybintio) ahead of the scheduled ESMO poster presentation.

Positive results emerging on oncology biosimilars will be presented at the European Society for Medical Oncology Virtual Congress 2020 this week . 

Positive Equivalency Data for a Trio of Biosimilars Are Reported

With the world’s pharmaceutical industry turning its eyes toward 

 for coronavirus disease 2019 (COVID-19), authors of a commentary piece urge investigators to prioritize investigating anti–tumor necrosis factor (TNF) therapies.

“The potential of anti-TNF therapy as a treatment for COVID-19 is supported by both biological plausibility and observational clinical data

. "Few current treatments under investigation have this level of supportive evidence."

Anti-TNF drugs, such as reference and biosimilar versions of infliximab, etanercept, and adalimumab molecules, are used to neutralize TNF, a cytokine signaling protein that causes inflammation related to a number of rheumatic conditions including rheumatoid arthritis, psoriatic arthritis, plaque psoriasis, ankylosing spondylitis, and inflammatory bowel disease (IBD).

“There is a long history of safe use of anti-TNF therapy in a diverse range of diseases, and supply is plentiful with many originator products available as well as many biosimilars

 "Anti-TNF therapy now has huge potential. We need to urgently investigate its value through prioritization of clinical trial resources worldwide."

COVID-19–related inflammation is linked to elevated concentrations of TNF as well as interleukin (IL)-6 and IL-8. The authors noted that a major component leading to COVID-19–related lung deterioration is capillary leak as a result of inflammation caused by these key cytokines.

Capillary leak involves the release of fluid and proteins from tiny blood vessels into surrounding tissue, potentially leading to dangerously low blood pressure; low albumin, a protein made by the liver; and low plasma volume.

“It is therefore conceivable that anti-TNF therapy could reduce inflammation-driven capillary leak in COVID-19 and have a major impact on the need for ventilation and mortality,” wrote the authors.

Data from the SECURE-IBD registry suggested that patients with IBD who are on anti-TNF therapies and develop a COVID-19 infection have equally good or better results compared with those using other agents.

Researchers found that anti-TNF therapies were inversely associated with the composite outcome of death or hospital admission for COVID-19 (adjusted odds ratio [OR] 0.60; 95% CI, 0.38-0.96; 

= .03). However, they did not affect the composite of intensive care admission, ventilation or death, and death alone.

Data from the COVID-19 Global Rheumatology Alliance registry on 600 patients with rheumatic diseases showed that anti-TNF therapy, used alone or in combination with other immunomodulatory drugs, was associated with a lower rate of hospital admission for COVID-19 (adjusted OR of 0.40; 95% CI, 0.19-0.81; 

= .01) than for patients who did not use disease-modifying antirheumatic drugs.

When anti-TNF agents were used as monotherapy, the adjusted OR went down to 0.30 (95% CI, 0.11-0.79; 

A smaller trial of 77 patients with COVID-19 found that 40% and 13% those using non-TNF drugs for a pre-existing condition required ventilator support or died, respectively.

Although these trials are meaningful and important, there are many underway of all types, and patient recruitment challenges are anticipated.

, a randomized trial investigating the effects of a biosimilar infliximab (Remsima) in patients with COVID-19, is currently recruiting in the United Kingdom, where hospital admissions are low and accrual is expected to be slow.

A study is also ongoing at Tufts Medical Center in Boston, Massachusetts, in 17 patients and a prehospital study is planned in the United Kingdom to establish whether anti-TNF therapy can prevent milder COVID-19 cases from becoming severe.

“The potential of anti-TNF therapy as a treatment for COVID-19 is supported by both biological plausibility and observational clinical data. Few current treatments under investigation have this level of supportive evidence,” wrote the authors.

The data from the SECURE-IBD and COVID-19 Global Rheumatology Alliance registries also have limitations in that comparators consist of other patients with rheumatic diseases or IBD. Those comparators may respond differently to COVID-19 due to changes in their immune system.

Also, patients with rheumatic diseases who take anti-TNF therapies likely have been on these therapies for a considerable amount of time prior to contracting COVID-19, making it hard to discern whether a first administration of anti-TNF therapy would yield the same results.

“It is therefore unknown whether the anti-TNF therapy results found in these registries are generalizable to the public,” the authors noted.

The number of current case reports on the use of anti-TNF therapies in patients with COVID-19 is small.

Robinson PC, Richard D, Tanner HL, Feldmann M. Accumulating evidence suggests anti-TNF therapy needs to be given trial priority in COVID-19 treatment. 

. Published online September 4, 2020. doi:10.1016/ S2665-9913(20)30309-Xpubm

With anti–tumor necrosis factor (TNF) therapy showing promise in treating coronavirus disease 2019 (COVID-19), authors called for these agents to have a higher priority in research.

Opinion: Anti-TNF Therapies Need COVID-19 Trial Priority 

positive phase 3 exploratory study results for its bevacizumab biosimilar, Aybintio, which received European Commission 

The findings are set for presentation at the European Society for Medical Oncology (ESMO) Virtual Congress 2020, which begins this week.

The Incheon, Republic of Korea–based company said the study results supported preexisting evidence in support of equivalence between Aybintio and reference bevacizumab in patients with metastatic or recurrent nonsquamous non–small cell lung cancer.

“The data observed in the phase 3 exploratory analyses reinforce equivalent clinical efficacy between Aybintio and reference bevacizumab,” said Seongwon Han, vice president and leader of the Medical & Lifecycle Safety Team at Samsung Bioepis.

The exploratory study enrolled 665 patients, of whom 337 received Aybintio and 328 were treated with reference bevacizumab with paclitaxel and carboplatin every 3 weeks for up to 6 cycles, followed by Aybintio or reference bevacizumab maintenance monotherapy. The risk difference was analyzed in the per-protocol set (PPS) within a predefined equivalence margin of ±12.5%.

The primary end point was overall response rate (ORR) after 24 weeks of induction therapy. In a previous analysis, the ORR in the PPS was 50.1% for Aybintio and 44.8% for reference bevacizumab, and the risk difference by week 24 was 5.3% (95% CI, 

2.2% to 12.9%). The risk difference is a comparative measure of the likely harms and benefits of therapies.

In the current study, the risk differences in best ORR by weeks 11 and 17 was 2.2% (95% CI, 

The mean reduction in tumor burden by week 24 was 

27.3% for reference bevacizumab, with a difference of 0.59% (

Samsung Bioepis said the results of the phase 3 exploratory analyses would be presented in an e-poster at ESMO during the virtual event’s Science Weekend on Thursday, September 17 at 9 AM Central European Summer Time.

Samsung Bioepis' bevacizumab biosimilar demonstrates equivalence in analyses to be presented at the European Society for Medical Oncology Virtual Congress 2020.

Samsung Bioepis Reports Positive Phase 3 Results for Aybintio

Being based in Europe can have unique challenges for a company like Polpharma Biologics, a contract development and manufacturing organization (CDMO) with facilities in Poland and the Netherlands that specializes in biologics. Despite facing hurdles such as navigating partnerships to commercialize in multiple markets, developing complex molecules for international partners, and figuring out how to handle coronavirus disease 2019 (COVID-19) with facilities in 2 countries, Polpharma Biologics has grown to become a powerhouse, having 7 biosimilars in its pipeline and partnerships with Sandoz and Bioeq.

We sat down with Alexandra Moulson, vice president of Strategy, Programs, and Portfolio at Polpharma Biologics to discuss how Polpharma Biologics and other CDMOs function and how companies choose which molecules to develop.

To check out more of our coverage of Polpharma Biologics, click 

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To learn more about Polpharma's natalizumab clinical trial, click 

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To learn about Polpharma Biologics recent integration efforts, click 

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To learn more about Polpharma Biologics, click 

Podcasts

We sat down with Alexandra Moulson, vice president of Strategy, Programs, and Portfolio at Polpharma Biologics to discuss how Polpharma Biologics and other contract development and manufacturing organization (CDMOs) function and how companies choose which molecules to develop.

Not So Different: Alex Moulson on How Companies Choose Which Biosimilars to Produce

April E. Weisbruch is a partner at McDermott, Will, & Emery LLP. She focuses her practice on intellectual property (IP)  matters, particularly in managing large-scale IP litigation and counseling. She works with clients in wide-ranging technology sectors, including pharmaceuticals, software applications, medical devices, organic chemistry and ballistics. April represents clients in all phases of patent litigation, from the filing of a complaint through appeal, as well as in the highly specialized post-grant proceedings before the United States Patent Trial and Appeal Board (PTAB). She has extensive deposition, hearing and trial experience in US district courts throughout the country, as well as in the US Court of Federal Claims, the US Court of Appeals for the Federal Circuit, and the PTAB. Her litigation experience includes traditional "competitor" litigation, litigation against nonpracticing entities, ANDA litigation under the Hatch-Waxman Act and §1498 litigation against the United States of America.

A number of legal trends have emerged in biologics litigation over the summer. Below we discuss 5 of the most significant.

One Notice Is Sufficient if the Underlying Biologic Remains the Same

Under the Biologics Price Competition and Innovation Act of 2009 (BPCIA), one step of the infamous “patent dance” requires a pharmaceutical company seeking to market a biosimilar product to notify the biologics product reference application holder “not later than 180 days before the date of the first commercial marketing” of the biosimilar. But does an applicant have to renotify the reference product sponsor when it supplements its initial abbreviated biologics license application (aBLA)? That was the issue posed to the United States Court of Appeals for the Federal Circuit in 

Genentech Inc v Immunex Rhode Island Corp.

The court ultimately concluded no additional notice is required.

Immunex (a company acquired by Amgen) filed an aBLA with the FDA and subsequently notified Genentech, the reference drug sponsor for Avastin®, that it intended to market a biosimilar version, Mvasi™. After providing its initial notice, Amgen submitted 4 supplemental applications, which included changes to the manufacturing facility and label. Genentech filed an emergency motion seeking to preclude Amgen from commercially marketing Mvasi™, arguing that Amgen did not provide proper commercial notice because the supplemental applications amending the manufacturing facility and label effectively reset the 180-day period. The district court disagreed, and on appeal, the Federal Circuit affirmed the decision. According to the Federal Circuit, supplemental applications do not require a new notice so long as the biological product that is the subject of the application does not change.

Practically speaking, the Genentech decision is a relief to biosimilars companies that may previously have been fearful that an aBLA cannot be amended during the normal FDA regulatory review process. That said, the court did not provide clear guidance about when the biological product has undergone a change sufficient to require a second notice of commercial marketing. Thus, beyond the facts of 

, the precise contours of when an aBLA supplement may require renewed commercial notice still remain to be seen.

Don’t Invalidate Your Biologics Patents by Licensing Them

It’s well known that biologics patent portfolios are extensive, and that licensing them can be quite lucrative for the patent owner and the licensee manufacturer. But a recent case serves as a stark reminder that companies must nevertheless be cautious when licensing patents, lest they accidentally invalidate their own portfolio through common ownership.

Under the doctrine of statutory double patenting, a patent is invalid if it covers subject matter identical to another patent owned by the same entity. This concept was implicated in 

, where the primary issue was whether, by a transfer of rights from Hoffman-La Roche in the 1990s, Immunex alone owned patents-in-suit covering Enbrel® (etanercept).

 Because Immunex owned other patents that covered the same technology, if Immunex had owned the asserted patents outright, Sandoz may have been able to invalidate the asserted Enbrel® patents on grounds of statutory double patenting.

Considering this among other issues, the Federal Circuit determined that the Roche-Immunex license did not transfer “all substantial rights” to Immunex, thus eliminating a statutory double-patenting defense. The license at issue granted Immunex an irrevocable, exclusive license and control over the prosecution of the pending Enbrel® patent applications. The agreement also granted Immunex the right to sublicense the patents and the first right to sue any potential infringers. Notably, Roche was obligated to cooperate with any prosecution and enforcement of the patents and retained a secondary right to sue if Immunex did not file suit. Roche also retained the ability to object to any sublicenses for the patents.

In its analysis, the majority gave significant weight to Roche’s retention of a secondary right to sue and the ability to prevent Immunex from further licensing the patents. Because these rights are inconsistent with the transfer of all substantial rights for a patent, the court reasoned, Immunex was not an owner. In dissent, Judge Jimmie V. Reyna argued that the license transferred all substantial rights to Immunex, rendering it the sole owner of the asserted patents.

This case shows that companies must be diligent when entering license agreements and appropriately structure such agreements to avoid being considered an owner if the covered matter substantially overlaps with existing portfolio assets. Indeed, in the case of large biologics portfolios, such caution is all the more necessary.

By their nature, biologics portfolios are large; AbbVie’s Humira® (adalimumab) is covered by approximately 247 patent applications that resulted in 132 patents, over 100 of which trace back to just 20 original applications. So, it was no surprise that after AbbVie settled several large-scale litigations relating to Humira® with a variety of biosimilars companies, a group of indirect purchasers sued in federal court alleging that the settlements were antitrust violations.

What was surprising, however, were the plaintiffs’ theories about the case. To be sure, the plaintiffs asserted the typical claim that the settlements were illegal restraints of trade, an argument that failed because the district court concluded that AbbVie’s settlements (which permitted competitors to immediately enter the European market but refrain from entering the US market until 2023) were not unlawfully anticompetitive. However, the plaintiffs also advanced a second, more creative theory: that AbbVie impermissibly monopolized the domestic market for Humira® by obtaining and asserting invalid, unenforceable, or noninfringed patents without regard to the merits of such assertions. This argument likewise failed. The district court found that AbbVie’s conduct was not objectively baseless for multiple reasons, including because the United States Patent and Trademark Office had granted more than half of AbbVie’s patent applications and a substantial majority of the patents challenged in inter partes review proceedings had survived. These successes convinced the district court that AbbVie’s conduct was not unreasonable and shielded AbbVie from antitrust scrutiny.

The plaintiffs filed a notice of appeal this past July, and a decision from the United States Court of Appeals for the Seventh Circuit is expected sometime next year. If this decision stands on appeal, it could potentially encourage biologics companies to create judicially sanctioned dense patent portfolios. In any event, biologics companies should have a focused and well-defined strategy when developing new products to ensure that they can reap the full benefits of patent protection while simultaneously avoiding antitrust exposure.

Federal Circuit Reaffirms That Common, Broad Claim Terms Are Broadly Construed

The Federal Circuit delivered a recent victory to patent owners seeking to give broad scope to the meaning of common terms in patent claims. At issue on appeal were the district court’s constructions of the terms 

 in a patent asserted by Baxalta purportedly covering Genentech’s Hemlibra® (emicizumab).

 Notably, the district court opinion was issued by Federal Circuit Judge Timothy B. Dyk, who was sitting by designation in the District of Delaware.

The district court had concluded that without structural context, the term 

 had multiple, commonly accepted meanings. Choosing between Baxalta’s broad proposal—“molecule having a specific amino acid sequence comprising two heavy chains (H chains) and two light chains (L chains)”—and Genentech’s narrower one—“immunoglobulin molecule, having a specific amino acid sequence that only binds to the antigen that induced its synthesis or very similar antigens, consisting of two identical heavy chains (H chains) and two identical light chains (L chains)”—the district court sided with Genentech. In doing so, it relied primarily on 2 pieces of evidence: (1) the specification’s description of 

 and (2) a claim amendment made during prosecution.

On appeal, the Federal Circuit unanimously reversed the ruling. Placing nearly dispositive weight on the claim language of 

 (which does not itself require 2 identical heavy chains and 2 identical light chains or binding only the antigen that induced its synthesis or similar), the court found no reason to limit the plain meaning of the term. It drew additional support from language in a dependent claim identifying certain subsets of antibodies that fell outside the district court’s construction of the term 

. Although the district court would have reconciled the difference by invalidating the inconsistent claims, the Federal Circuit instead found that they provided significant evidence of the breadth of the term. And contrary to the district court, the Federal Circuit refused to adopt a definition excluding claimed embodiments and disagreed that the prosecution history clearly limited the scope of the claim.

Although claim construction is a patent-specific inquiry, the Federal Circuit’s opinion reaffirms that broad terms will be given broad meaning absent a reason demonstrating that the patentee intended otherwise.

New Regulations for Biologics Are (Possibly) Coming

Earlier this year, the FDA announced that it intended to issue substantive regulations governing biologics to clarify existing requirements and procedures related to BLAs.

 The proposed rules are expected to be released in December 2020. The update would further “promote the goals associated with the FDA’s implementation of the abbreviated licensure pathway created by the” BPCIA. But with the details still in the works, it is unclear what changes the FDA intends to make. Certainly, with a relatively low rate of market penetration and cost savings to would-be biosimilar consumers, there could be much worth considering. Although the FDA has yet to issue any proposed rules, industry stakeholders should continue to monitor the agency’s proposed regulations to determine how the regulations could affect the biologics industry.

In sum, this has certainly been an interesting summer for biologics. From basic statutory interpretation to antitrust issues, the legal and business landscape for biologics continues to evolve at a rapid pace. Companies must remain adaptable and continually take appropriate measures to position themselves for future success.

Genentech Inc v Immunex Rhode Island Corp

In re Humira (Adalimumab) Antitrust Litigation

, Appeal No. 2019-1527 (Fed Cir August 27, 2020).

Biologics Regulation Modernization. Reginfo.gov. Accessed September 2, 2020. https://www.reginfo.gov/public/do/eAgendaViewRule?pubId=202004&RIN=0910-AI14

Intellectual property law attorneys from the Washington, DC, offices of McDermott Will & Emery LLP, discuss 5 of the most significant trends in biologics litigation that have emerged in recent months.

What We Learned About Biologics on Summer Vacation

 to find treatments for coronavirus disease 2019 (COVID-19), Incheon, Republic of Korea–based Celltrion Healthcare said a phase 1 trial for its monoclonal antibody treatment (CT-P59) showed positive results for safety, tolerability, and pharmacokinetics.

This comes as the company’s infliximab biosimilar (Remsima) is currently under evaluation in the 

 trial for potential in treating patients with COVID-19-related inflammation during hospitalization.

“Whilst the CATALYST trial aims to show that our drug could delay or prevent the rapid deterioration into intensive care for hospitalized patients, our antiviral antibody treatment aims to prevent the infection and proliferation of COVID-19. However, both involvements are for the same objective: to bring our full resources and expertise to overcome this global health crisis and dedicate our efforts to support health care systems across the world,” said Byoungseo Choi, head of marketing for Celltrion Healthcare in a recent 

The phase 1 randomized, double blind, placebo-controlled trial evaluated the safety of CT-P59 in healthy subjects. Study results demonstrated that CT-P59 did not cause any significant drug-related adverse events. Additionally, there were no adverse events in the maximum-tolerated-dose cohort.

“Along with these promising safety results, we have launched commercial production of CT-P59 this month to ensure, if trials are successful, we can meet the urgent global demand for a safe and effective antiviral treatment against COVID-19,” said Sang Joon Lee, PhD, senior executive vice president of Celltrion, in a statement.

Lee said that Celltrion plans to request emergency use authorization for CT-P59 if positive results continue to be seen during its other ongoing clinical trials.

Celltrion has so far initiated an in-human, global phase 1 clinical trial of CT-P59 in patients with mild cases of COVID-19 and said that it plans to conduct global phase 2 and phase 3 trials in 500 patients from 12 countries, including the Republic of Korea.

Celltrion said it anticipates enrolling a total of 3000 patients in clinical and prevention trials, which will investigate whether CT-P59 can be used as a preventive treatment for COVID-19 for those in close contact with patients who have the disease.

Celltrion said it aims to complete the development of CT-P59 by the first half of 2021. The company 

 it was joining the race to develop a COVID-19 antibody treatment in April and 

 to complete the phase 1 trial for CT-P59 by the end of the third quarter of 2020.

The news comes several weeks after Celltrion announced it would 

 a phase 1 trial in September for its osteoporosis biosimilar (CT-P41) referencing Prolia.

Alos, in August, Celltrion said that it is collaborating with Intract Pharma to develop the world’s first oral infliximab for the treatment of inflammatory bowel disease.

This year, the World Health Organization prequalified 2 of Celltrion’s biosimilars, including its trastuzumab (

 in the United States in March for the treatment of HER-2 positive breast cancer, and its rituximab molecule (

) for treating non-Hodgkin lymphoma and chronic lymphocytic leukemia.

In the effort to find treatments for coronavirus disease 2019 (COVID-19) and related conditions, Celltrion Healthcare’s monoclonal antibody has shown promise in a phase 1 trial.

Celltrion’s COVID-19 Antibody Treatment Shows Positive Results

In a quest to ensure that product labeling disclosures about biosimilars are not unduly influencing the opinions of health care providers (HCPs) and consumers toward biosimilars, the FDA aims to conduct a study that will examine HCP and consumer responses to different types of label wording.

 about the draft outlines for the study, various pharmaceutical companies and groups have offered their suggestions for improving the value of these studies and upgrading standard biosimilar disclosures so that unwarranted perceptions do not form in the minds of HCPs and consumers.

“In the context of prescription drug promotion, there is initial evidence that—when noticed—disclosures may effectively convey important information; however, what role disclosures may play in educating or correcting misunderstanding warrants further investigation,” the FDA stated in describing the purpose of the study.

Promotional claims about biosimilars have been a focus for the FDA and Federal Trade Commission this year, as they endeavored to 

 to industry concerns that the public’s perception of biosimilars has been warped by multiple factors, including unintentionally and deliberately misleading promotions, from regulatory language to competitors’ claims about biosimilars.

The FDA plans to examine how label claims about nonprimary investigative goals, or secondary end points, in clinical studies will affect perceptions among HCPs and consumers. Participants enrolled in the study will view different versions of a website showing information about a fictitious product and answer questions based on their perceptions of that information.

The second part of the study will evaluate how disclosing that a drug product is a biosimilar affects HCP and consumer perceptions. Participants will also be asked to respond to various informational statements about biosimilars.

Study participants will also be asked for their reactions to multiple versions of language describing biosimilars and their relative safety and efficacy to reference products.

“This approach allows us to examine the effect of disclosing biosimilar status, examines the additive effect of including 1, 2, or 3 additional basic statements of information about biosimilars, and measures the effect of naming the reference product,” the FDA wrote.

In public comments about the study proposal, the Biosimilars Forum, representing biosimilars developers, said it was concerned about how language used to describe biosimilars may be “couched in cautionary or negative terms,” which hold the potential to be off-putting to HCPs and consumers.

It asked for a stronger emphasis in the study on garnering patient perceptions of biosimilar disclosures. “In the 6 years since the Forum was founded, we have found that while knowledge and perceptions of HCPs have increased…knowledge levels of patients are still low,” the group wrote.

Similarly, the drug company Bayer commented that the language of the study as it would be presented to participants sounded clinical and should be rewritten for consumer participants so that it was “patient friendly.”

The Hematology/Oncology Pharmacy Association asked that the study also evaluate the value of adding information about use of biosimilars for all indicated uses, or extrapolations, of the reference product. “Several studies have indicated that understanding, or lack of understanding of biosimilars in extrapolated indications, impacts a health care professional’s use of a biosimilar,” the group said.

A further critique of the study came from the Pharmaceutical Research and Manufacturers of America, which contended the study will not provide useful information because such information is already available to the FDA from other sources, the proposed study as designed is "flawed" because secondary end points are more important to a product’s indicated uses than the study design seems to suggest, and the study unfairly uses a genuine product, Humira (adalimumab) as a case example while using an anonymous or fictitious biosimilar.

That last point also drew an objection from AbbVie, which owns the Humira brand. The “FDA should refrain from using the name of a reference product currently on the market in the questionnaire and instead use a fictitious name for a reference product, as it does for the biosimilar,” the company said.

The importance of getting label language right for biosimilars is illustrated by the problem with consumers' understanding of alternative health products, the FDA noted. "

Research on consumer attitudes [has] found some people believe that FDA evaluates certain dietary supplement claims despite the presence and consumer awareness of language required by the Dietary Supplement Health and Education Act, which clearly states that FDA has not evaluated those claims."

Trade associations and companies in the biosimilars business ask the FDA to hone its proposed study on product disclosures.

FDA Draft Study on Biosimilar Disclosures Draws Fire

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.

Here are the top 5 biosimilar articles for the week of September 7, 2020.

Number 5: Authors of a report on Medicare spending trends said there’s more to 

 of insulin than instituting out-of-pocket (OOP) caps.

Number 4: A review of changes in business practices by PBMs states that apparent reforms have been undermined by 

 arrangements that have stalled placement of biosimilars on formulary and slowed uptake.

Number 3: Bio-Thera Solutions has begun a 

 for its proposed ustekinumab biosimilar (BAT2206), referencing Stelara, which is used in the treatment of plaque psoriasis and psoriatic arthritis.

interviewed several experts for their opinions on the current need for biosimilars and how companies are working to overcome barriers to uptake.

Number 1: Some European markets are more formidable than others with regard to complexity and getting biosimilars established, but there are 

, Jonathan Sweeting, head of Europe for Samsung Bioepis, explains.

To read all of these articles and more, visit 

The Top 5 Biosimilar Articles for the Week of September 7

Suzhou, China-based Innovent Biologics said that its adalimumab biosimilar (Sulinno) has received marketing approval from China’s National Medical Products Administration (NMPA).

“The launch of Sulinno once again fulfilled our mission to develop and commercialize high quality biopharmaceutical products that are affordable to ordinary people. We hope that this product will benefit more and more patients and families in need and improve their quality of life,” Michael Yu, chairman and CEO of Innovent, said in a 

The drug referencing Humira is a recombinant human anti–tumor necrosis factor–alpha monoclonal antibody injection. Sulinno has been approved by the NMPA for the treatment of rheumatoid arthritis, ankylosing spondylitis, and psoriasis.

This latest approval moves the company's biosimilar portfolio a notch higher in the lucrative Chinese market. 