Regeneron's Eylea HD Faces Setbacks, But Company Remains Optimistic

Regeneron Pharmaceuticals has encountered another obstacle in its quest to bring the high-dose (HD) version of its blockbuster drug Eylea to market. The U.S. Food and Drug Administration (FDA) has issued a complete response letter (CRL) for the pre-filled syringe formulation of Eylea HD, citing manufacturing issues at a third-party facility. Despite this setback, the company is actively pursuing alternative manufacturing solutions and remains confident in the drug's future.

Manufacturing Challenges and FDA Rejection

The rejection stems from unresolved issues at a Novo Nordisk manufacturing plant in Bloomington, Indiana, which Novo acquired from Catalent in late 2024. Earlier this month, Novo informed Regeneron that the FDA had classified the facility with an Official Action Indicated (OAI) status, the most severe of the agency's inspection classifications. This classification suggests that the facility is in an "unacceptable state of compliance," with violations including persistent contamination issues and lack of preventive mechanisms.

This latest CRL follows a previous delay announced in August 2025, when Regeneron revealed that the FDA had extended its decision deadline for two Eylea applications from August to the fourth quarter of 2025 due to the same manufacturing concerns.

Regeneron's Response and Alternative Manufacturing Plans

Despite the regulatory hurdles, Regeneron CEO Leonard Schleifer struck an optimistic note during the company's Q3 earnings call. The pharmaceutical giant is actively working on solutions to address the manufacturing issues:

1. Regeneron plans to submit an application in January 2026 for an alternate pre-filled syringe filler, which would trigger a four-month FDA review.

2. The company is also tapping an alternate vial filler for an ongoing review, with the FDA having a target action date in late December 2025.

3. Regeneron is expanding its manufacturing capabilities, including a $3.6 billion expansion of its Tarrytown, New York campus and the construction of a new fill-finish facility in Rensselaer, New York.

4. In April 2025, Regeneron signed a $3-billion, 10-year deal with Fujifilm for bulk drug production at its complex in Holly Springs, North Carolina.

Schleifer emphasized the company's long-term strategy to gain the ability to manufacture all of its products in-house, stating, "We've been talking about the need for domestic manufacturing since 2014 in testimony before Congress."

Financial Impact and Market Response

Despite the regulatory challenges, Eylea HD sales in the United States have shown positive trends, reaching an all-time high of $431 million in the third quarter of 2025. However, this increase has not fully compensated for the erosion in sales of the original version of Eylea, which fell 41% year-over-year to $681 million.

Regeneron's overall sales grew 1% to $3.75 billion in the third quarter, driven primarily by strong performances from Dupixent (up 27%) and Libtayo (up 26%). The market responded positively to Regeneron's proactive approach to addressing the manufacturing issues, with the company's shares rising 11.8% to $654.48 at the close of trading following the earnings call.

Analysts from BMO Capital Markets and Truist Securities expressed encouragement at Regeneron's efforts to secure new manufacturing facilities for Eylea HD, suggesting that these moves could signal an end to the manufacturing troubles that have plagued the franchise since 2023.