The expiration of the U.S. substance patent for the blockbuster biopharmaceutical Eylea (aflibercept) is expected to spark competition in the biosimilar market.

Samsung Bioepis, which preemptively received marketing authorization for an Eylea biosimilar, is stuck in a patent dispute with Regeneron, which owns the original Eylea. It is expected that other latecomers will also face a tough time entering the market depending on Regeneron’s patent response.

Eylea is a treatment for eye diseases such as macular degeneration that binds to vascular endothelial growth factor (VEGF) and inhibits neovascularization. The drug generated global market sales of KRW 13 trillion. Of these, the U.S. market accounts for USD 5.719 billion in sales, accounting for a 62% share.

Currently, Eylea’s patent has expired in Korea and its biosimilar has been launched into the market, and the patent is scheduled to expire in May 2025 in Europe.

In the U.S., the product patent expired in June of this year, but the other patents will expire as follows: ▲formulation patent in 2027, ▲ regimen patent in 2032, ▲purification and batch patent in 2040

The difference between biosimilar entry in Korea and the United States is in the existence of patent disputes. In Korea, Bayer, which sells Eylea, did not file a patent suit, so there was no problem with the launch of Eylea biosimilars.

However, in the U.S., Regeneron filed a patent infringement lawsuit against Celltrion and Samsung Bioepis in November last year.

Regeneron patent defense remains a hurdle in the Eylea market...launch timing remains in question

Samsung Bioepis is the company facing an immediate issue due to the patent suit. In May, the U.S. Food and Drug Administration (FDA) approved Samsung Bioepis' Eylea biosimilar, Opuviz, along with India's Biocon Biologics' Yesafili, as the first biosimilars.

However, on June 15, the U.S. District Court for the Northern District of West Virginia granted Regeneron's motion for a preliminary injunction against Samsung Bioepis, which prevents Opuviz from launching in the United States.

Samsung Bioepis immediately filed an appeal against the preliminary injunction, but the appeal is expected to take 6 months to a year.

A Samsung Bioepis official said, “We have no position on the patent dispute that we can disclose at this time.”

While it is difficult to predict the outcome of the patent dispute, the general consensus is that the ruling aligns with Regeneron’s intent as the request for a preliminary injunction has been granted.

"In the current situation where the product patent has already expired, it is important to determine whether the formulation patent is infringed, and Samsung Bioepis or Celltrion must prove that the patent has not been infringed," said an official from the Korean Intellectual Property Office. "Regeneron's strategy will be to delay the launch of the similar by claiming patent infringement."

"In addition to the remaining formulation patent, Regeneron's dosing regimen patent expires in 2032, among others, so the company has an evergreen strategy in place and does not need to hasten the process. The Korean company can appeal to the federal court, but that will also take time, so the originator has an advantage."

Considering this, it is difficult to gauge the exact timing of Opuviz’slaunch as its launch is banned until the end of the patent dispute.

Given the nature of biosimilars, where multiple competitors enter the market at the same time, it is important to arrive first into the market. However, in this situation, it is unclear whether the biosimilar companies will be able to enjoy the advantage of first approval.

The industry believes this is a red flag for Celltrion as well, as the company has also completed applying for U.S. FDA marketing authorization for its biosimilar.

However, the result may differ, as there have been cases like Humira where the original and generic companies discussed royalty payments to enable earlier market launch of the generics.

AbbVie had delayed the launch of Humira biosimilars beyond the product patent term by building a patent barrier, but Amgen agreed to pay royalties on the remaining patents and released the first Humira generic.

"At the time, the industry expected Humira’s generic release to be a long battle as well, but discussions were dramatically held, allowing for the generic’s launch last year,” said an industry official. "If the company feels that it has been extended Eylea’s patent long enough, there is a possibility that the timing of the launch of its generics could be coordinated through similar discussions.”