Biosimilars in the United States: Current Status and Future Implications

Biosimilars in the United States: Current Status and Future Implications

June 10, 2019
8 min read

Battle for Enbrel: Ruling on patent lawsuit could transform US biosimilar marketplace

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Amgen is currently embroiled in two pivotal court cases surrounding patents for its bestselling etanercept product that could protect it from competition in the United States for another decade. Determined to defend the commercial exclusivity of its blockbuster biologic against biosimilars offered by Novartis and Samsung Bioepis, Amgen has become increasingly mired in litigation against its would-be competitors — a legal battle whose outcome could have monumental impacts on the U.S. biosimilar market.

In September 2018, Amgen entered into patent litigation against the Sandoz arm of Novartis concerning its biosimilar Erelzi (etanercept-szzs), claiming patent infringement on Enbrel (etanercept). Claire C. Cecchi, U.S. District Court judge for the District of New Jersey, is expected to issue a final ruling sometime in 2019 on whether Erelzi will be allowed to enter the U.S. market, or whether Amgen holds exclusive patent rights for etanercept. More recently, Amgen filed a similar lawsuit against Samsung Bioepis for its etanercept biosimilar, Eticovo (etanercept-ykro), but this case has not yet reached the courts.

The impetus for this litigation is simple: Amgen hopes to hold market exclusivity for the molecule through 2029. Although the primary patent on Enbrel was filed in 1990 — and expired in 2010 — Amgen also holds 19 active patent applications and approved patents that could effectively guard Enbrel’s commercial exclusivity in the U.S. for another decade.

Alisha Kay Taylor

“The ruling in Amgen v. Sandoz will no doubt have an impact on the litigation strategy Amgen adopts as it goes forward against Samsung Bioepis,” Alisha Kay Taylor, an attorney at Richards Patent Law PC, told Healio Rheumatology. “Depending on the pending ruling, one party may have significantly more leverage for settlement. The ruling may not only have huge ramifications on the multibillion dollar Enbrel business of Amgen, but for biologics at large.”

However, the litigations involving Enbrel are only two of a number of past and pending bio-originator/biosimilar legal matters that are shaping both medical patent law and the pharmaceutical marketplace. These legal issues stem from the 2009 Biologics Price Competition and Innovation Act (BPCIA), which established the biosimilar market in the U.S. by allowing a pathway to the market for large-molecule drugs.

Since then, a number of cases have shaped the real-world implications of the law, perhaps the most significant component of which involves the so-called “patent dance,” in which the manufacturers of the bio-originator and biosimilar take a 6-month period to share patents and determine whether the biosimilar infringes on the reference product. In the Erelzi case, Novartis participated in the patent dance. As Erelzi has been launched in both Canada and the European Union without incident, experts noted that the drug is poised to launch in the U.S. market should the court rule in its favor.

Driving the Enbrel-Erelzi case is the make-up of the drug, which is the result of the fusion of two proteins: a human antibody and a TNF receptor. Amgen argues that this composition is key to Enbrel’s mechanism of action. Novartis argues that previous scientific discoveries made the patent obvious, in legal terms, and, consequently, invalid; Erelzi is also a fused TNF inhibitor.

The (Biosimilar) World is Watching

Even before Erelzi was approved by the FDA in August 2016, Amgen had already launched litigation against Sandoz, citing that its proposed biosimilar infringed on five Enbrel patents, including manufacture and treatment indications. In an attempt to nullify three of Amgen’s patent infringement claims outlined in its lawsuit, Sandoz amended the Erelzi label to “carve-out” allindications for psoriatic conditions — a label change subsequently approved by the FDA in January 2018.

However, as Amgen countered in a summary judgment reply brief, the damage had already been done and “cannot be retroactively undone.” According to Amgen, the FDA’s original approval disseminated information that “even though the only studies that Sandoz conducted were in plaque psoriasis, Sandoz’s etanercept is appropriate for use in psoriatic arthritis.” The legal precedents established in the Erelzi case will likely inform future biosimilar litigation, noted Taylor, with potential ramifications even for biosimilars still in development.

“A win for Amgen strengthens its patent portfolio by further solidifying its granted monopoly for the life of its remaining patents, including licensed patents,” Taylor said in an interview. “The ruling could also send a strong message to companies pursuing biosimilars and the ramifications of label carve-outs.”

Another possible impact could be, in the face of considerable legal hurdles while attempting to launch biosimilars, companies may be reluctant to invest in expensive research and development of biosimilars, thereby reducing competition, according to Taylor. “At the same time, a pro-patentee result would reinforce the traditional incentives of patent protection and market exclusivity as a quid pro quo of extensive and expensive drug development,” she said.


Alternately, a legal victory for Sandoz would allow the company to immediately launch a direct competitor biosimilar product, cutting away at a portion of Amgen’s profits, Taylor suggested.

“In the bigger picture, a win for the biosimilars may be viewed in the political climate as a step towards reducing drug prices and increasing market share of the generics,” she said. “However, the extent of the reduced price and increase in market share will be mitigated — compared to generic small-molecule drugs — as the number of competitors for biosimilars will be limited due to the substantial costs of FDA approval for biosimilars compared to the FDA approval of small-molecule drugs.”

Other Battlegrounds

This is not the first time Amgen and Sandoz have squared off over biosimilar disputes, having previously tangled over the first FDA-approved biosimilar, filgrastim-sndz (Zarxio, Sandoz), in 2017. In that case, Sandoz chose not to engage in the patent dance, and launched its drug without disclosure or resolution of patent issues: Amgen sued. The Supreme Court ruled in favor of Sandoz, a landmark case for the BPCIA and an early sign that the law may be on the side of biosimilars.

Specifically, the Court ruled that the manufacturer of the biosimilar could opt out of the patent dance if they believed that the new drug lies outside of the patent covering the reference drug. Many experts believe that this gives the biosimilar developer the upper hand in the proceedings, given that they are not required to disclose information to the potential competitor before taking the drug to market.

The fact that both companies allowed the Zarxio dispute to move past the patent dance and all the way to the Supreme Court provides some indication that they may be willing to battle each patent case just as vigorously. There has been much speculation about the implications of the Zarxio case from a legal perspective, and what this may mean for current and future biosimilar cases.

A spokesperson from the Association for Accessible Medicines (AAM) addressed the issue in an interview with Healio Rheumatology. “Infringement requires a claim-by-claim analysis after a court undergoes a process known as claim construction,” they said. “As part of that analysis, each patent and set of claims needs to be assessed individually and specifically. Moreover, the critical issue is not infringement, but the number and types of patents that branded companies have obtained.” 

In the Amgen complaint against Samsung Bioepis, Amgen alleges infringement under the BPCIA, along with failure to participate in the patent dance. They have requested that Samsung Bioepis cease making or marketing its etanercept biosimilar, Eticovo, for 180 days after notice of commercial marketing has been provided and the suit is finished. Amgen has also demanded a jury trial for this case.

In yet another case involving Amgen, biosimilar manufacturer Coherus BioSciences recently settled with the company in a trade secret case involving Amgen’s innovator pegfilgrastim (Neulasta). The case was pending in the Superior Court of California prior to the settlement.

In the 2017 dispute, Amgen claimed that Coherus had engaged in a conspiracy to steal the trade secrets for Neulasta while developing their own biosimilar pegfilgrastim-cbqv (Udenyca). Although Coherus denied the allegations at the time, the company noted that, following the settlement, it will continue to market their FDA-approved biosimilar and pay a royalty to Amgen over the next 5 years.

It may be worth noting that Amgen also has its own biosimilars in the pipeline, including drugs that imitate infliximab (Remicade, Janssen), rituximab (Rituxan; Genentech, Biogen), cetuximab (Erbitux, Eli Lilly), eculizumab and trastuzumab (Herceptin, Genentech). Many experts believe that the company is likely to end up on the opposite side of the table as these drugs make their way toward FDA approval and, ultimately, the market.

Impact on Competition

Stephen B. Hanauer

Even as the legal battle presses on, there remains widespread uncertainty among experts about how this lengthy litigation could impact competition in the marketplace, especially where pricing is concerned.

“When the first generic or biosimilar reaches the market the cost-reduction is not nearly as substantial as when there is more than one competitor,” Stephen B. Hanauer, MD, Clifford Joseph Barborka Professor of Medicine and medical director of the Digestive Health Center at Northwestern Feinberg School of Medicine, said in an interview. “Blocking other products to market will maintain pricing for both the originator and first biosimilar.”

However, even in a market where the biologic and its first biosimilar are the only two marketed options, biologics may still have the advantage. Because biosimilars are only therapeutically equivalent, medical providers may be reluctant to simply substitute the biosimilar for the brand name, thereby reducing biosimilar profits, according to Taylor. “Regardless, there is a strong argument that any competition will drastically improve the high-cost drug market,” she said. “Therefore, even a few more competitors to the brand name biologic would provide patients with lower cost options for treatment.”


For Hanauer, it may be useful to look at other bio-originator/biosimilar products as a reference for future market projections. “There are now several biosimilars to Remicade and Humira (adalimumab, Abbvie) on the market in Europe,” he said. “The price for TNF inhibitors has fallen more than 50%.”

Other experts have looked to legal matters pertaining to generic drugs for insight as to how cases will play out for bio-originators and biosimilars. However, the AAM spokesperson suggested that there are several key differences. “First, as noted above, the number and volume of asserted patents is frequently much greater in biosimilar cases compared to Hatch-Waxman cases,” they said. “Second, biosimilar cases typically involve a number of manufacturing patents.”

In addition to the patent dance, the spokesperson noted that there is no linkage in biosimilar cases. “This means that a biosimilar manufacturer can obtain final approval at FDA regardless of the status of the patent litigation,” they said.

At the moment, biosimilars in the U.S. market have not driven as significant declines in drug prices as in Europe, due in part to the considerable wall of patent protections erected by many of the prominent biologic manufacturers, according to Hanauer. 

“AbbVie is doing the same sort of patent protection for Humira in the U.S. against FDA-approved biosimilars,” he said. “It is anticipated that these biosimilars will enter the U.S. market around 2023. Meanwhile, AbbVie already has introduced next-generation cytokine inhibitors to the rheumatology market that are expected to compete with Humira in several indications, including inflammatory bowel disease.”

The AAM spokesperson likewise reflected on the legal stronghold established for Humira market exclusivity, which has effectively blocked any would-be biosimilar competitors from entering the market. “This is a drug that cost the Medicare program $2.7 billion in 2017,” they said. “Humira’s initial patent expired in 2016 and it has three FDA-approved biosimilars; however, all of the biosimilar manufacturers have settled to not launch until 2023 given the time and cost it would take to wade through AbbVie’s patent fortress.”

Regardless of how any of these battles play out, there is little doubt that competition will continue to be fierce across the marketplace, according to the AAM spokesperson. “Branded companies apply and receive numerous potentially noninnovative patents that extend their monopoly protection and block competition, despite no changes to the underlying molecule, route of administration, dosage, or safety and efficacy,” they said. “Biosimilar manufacturers must litigate their way through these thickets in order to launch their products. This is why there are currently 19 approved biosimilars but only seven on the market.”

Patent experts like Taylor are keeping close tabs on all of these cases. “Biologics are definitely in the spotlight as evidenced by the numerous pending litigations, new FDA guidelines on biologic interchangeability, as well as recent legislation,” she said. by Rob Volansky

For more information:

Stephen B. Hanauer, MD, can be reached at 676 N. St Clair Street – Suite 1400, Chicago IL, 60611; email:

Alisha Kay Taylor can be reached at Willis (Sears) Tower, 233 S. Wacker Dr., 84th Floor, Chicago, IL 60606;

The AAM spokesperson can be reached via Rachel Schwartz:

Disclosure: Hanauer reports associations with a number of device and pharmaceutical companies, including Abbvie, Amgen, Janssen, Novartis, and Samsung Bioepis. Taylor reports no relevant financial disclosures.