NJ Court Decision Means 3 Decades of Product Exclusivity for Enbrel

Samsung Bioepis will not be able to bring its etanercept biosimilar (Eticovo) to market in the United States until 2029, based on the outcome of litigation between the company and the makers of the reference product (Enbrel), a tumor necrosis factor (TNF)–inhibitor used for treatment of inflammatory and autoimmune disease.

The US District Court for the District of New Jersey has ruled in favor of a contention by Enbrel makers Amgen, Roche, and Immunex that Samsung Bioepis would infringe 2 key patents if it attempted to produce, sell, or import to the United States its biosimilar prior to 2029, which is when the patents expire.

Enbrel is approved for rheumatoid arthritis, polyarticular juvenile idiopathic arthritis, psoriatic arthritis, ankylosing spondylitis, plaque psoriasis, and pediatric plaque psoriasis.

The court decision marks the second setback in a year for biosimilar versions of etanercept. In May 2021, the US Supreme Court declined to reopen a Federal Circuit patent case between the reference product makers and Sandoz, which had unsuccessfully sought to bring the etanercept biosimilar Erelzi to market prior to 2029.

No Other Challengers

These were the only etanercept biosimilars and there are no others on the approval horizon, according to a November 2021 report by Amerisource Bergen.

Erelzi received FDA approval in August 2016, but the patent litigation had kept this product in the warehouse rather than on pharmacy shelves. Eticovo was approved in April 2019.

The court decisions mean another 7 years will pass before biosimilar versions of etanercept can enter the US market, which represents the largest etanercept market by volume of sales for Amgen. Amgen reported just under $5 billion in Enbrel revenues in 2020; of that, $4.9 billion came from the US market.

In the European Union, Enbrel is marketed by Pfizer, and Samsung Bioepis, Sandoz, and Viatris are marketing etanercept biosimilars there.

In their suit against Samsung Bioepis, the plaintiffs argued that 5 patents owned by Roche and Immunex faced infringement. All 5 of the patents were issued well after Enbrel was first approved by the FDA, in 1998.

The pivotal patents in the court’s ruling of infringement were both owned by Roche: US patent 8,063,182 (‘182), issued in 2011, and US patent 8,163,522 (‘522), issued in 2012.

TNF is a cell-signaling protein whose overproduction leads to autoimmune and other inflammatory diseases. Etanercept is a fusion protein that binds with TNF to inhibit inflammatory responses. Both patents concern this fusion protein (p75 TNF receptor) and its makeup.

The filing of drug patents subsequent to FDA approval has the effect of extending the product exclusivity life of an originator drug, as has happened in this case. By 2029, Enbrel will have had 31 years of exclusivity in the United States.

Under the Biologics Price Competition and Innovation Act (BPCIA) of 2009, novel biologics drugs are guaranteed 12 years of exclusivity from FDA approval, with the intention that competitors can come to market after the originator company has earned a reasonable return on its product development investment. But as the Enbrel case has demonstrated, manufacturers can find ways to extend exclusivity well beyond the BPCIA time limit.

Price Increases and Exclusivity

One consequence of extended patent protection for a reference product is that manufacturers have more freedom to raise prices, sometimes well above the rate of medical inflation.

In January 2021, the Institute for Clinical and Economic Review (ICER) reported that Enbrel was among 10 prescription drugs for which the wholesale acquisition cost increases between 2018 and 2019 were more than twice as high as the rate of medical inflation. Humira (adalimumab), another reference product that so far does not have US biosimilar competition, also was on that list.

ICER reported that the 2018-2019 net price increases for these drugs were 8.9% and 2%, respectively, contributing to an increase in US drug spending of $403 million and $66 million, also respectively.

In a brief statement describing the court decision, Samsung Bioepis said it was under court injunction not to make, use, import, or sell Eticovo until the etanercept patent protection expires. "We have no comment regarding the court decision," a company spokeswoman said.

The Center for Biosimilars® recently covered the updated report on drug price increases from ICER.