Patent Expirations Ignite Fierce Biosimilar Race for Eylea

As blockbuster ophthalmology drug Eylea (aflibercept) loses its patent protection, intense competition is emerging between Regeneron—the original developer—and global biosimilar makers. South Korean companies are moving swiftly to capture market share through legal challenges, settlements, and patent-avoidance technologies.

Eylea, used to treat eye diseases such as wet age-related macular degeneration and diabetic macular edema, generated roughly $9.5 billion annually before its U.S. substance patent expired in May 2025. To preserve exclusivity, Regeneron pursued an evergreening strategy—filing follow-up patents covering formulation, dosage, and indications to delay biosimilar entry.

Celltrion spearheaded efforts to dismantle this patent shield for its biosimilar Eydenzelt.

In 2022, it launched a patent-invalidation trial targeting Regeneron’s formulation patent, prompting Regeneron to abandon the claim. Celltrion subsequently succeeded in nullifying two additional angiogenesis-related patents, further weakening Regeneron’s defense.

Although the company later lost a separate formulation-patent case, it ultimately reached a settlement on October 24, concluding all disputes related to Eylea’s formulation and manufacturing process. The agreement grants Celltrion the right to launch Eydenzelt in the U.S. from December 31, 2026.

Evergreening—filing incremental patents to extend market exclusivity—is a standard tactic among original drug developers. To counter it, biosimilar firms pursue varied approaches: patent challenges, settlements, or design-around technologies.

Global competitor Amgen was the first to secure a settlement with Regeneron, gaining rights to launch Pavblu in 2026. Biocon and Mylan followed in April 2025 with their biosimilar Yesafili, and Sandoz announced a similar deal the following month.

In Korea, Samsung Bioepis faced a temporary injunction halting Korean sales of its Eylea biosimilar Opuviz (Afilivu). On October 30, however, the company won an appellate court ruling invalidating Regeneron’s formulation patent—marking a key step toward resuming sales. In the U.S., despite Regeneron filing over 50 patent-infringement suits, Samsung Bioepis continues its defense through multiple inter partes review (IPR) victories.

Meanwhile, Samchundang Pharm has avoided direct litigation by developing a design-around formulation. Its proprietary prefilled-syringe (PFS) technology enables Eylea biosimilar development without infringing Regeneron’s formulation patents—allowing an independent market route.

While evergreening often restricts biosimilar access, it can create new opportunities for technology licensors. Alteogen exemplifies this trend with its subcutaneous (SC) formulation platform, licensed to Merck (MSD) for Keytruda.

Merck used Alteogen’s SC technology to extend Keytruda’s market exclusivity as its main patents neared expiry—introducing a new SC version alongside the IV formulation and filing additional patents to delay competitors. Following FDA approval of Keytruda SC, Alteogen received hundreds of millions of dollars in milestone payments and is expected to earn ongoing royalties tied to global sales.

As more pharmaceutical giants adopt SC-formulation strategies to reinforce patent protection, Alteogen’s platform is poised to gain further value as a key partner in next-generation drug-delivery innovation.