Regeneron Delays Eylea HD Filing After FDA CRL

Regeneron Pharmaceuticals has announced a delay in its regulatory plans for the Eylea HD (aflibercept injection 8 mg) pre-filled syringe, following a Complete Response Letter (CRL) from the U.S. Food and Drug Administration (FDA). The update was included in the company’s third-quarter earnings filing.

FDA Raises Manufacturing Concerns, Not Product Safety or Efficacy

According to Regeneron, the latest CRL concerns unresolved inspection findings at the manufacturing facility operated by Catalent, the contract manufacturer for the pre-filled syringe. These manufacturing-related issues remain the sole approvability concern.

Earlier this year, in April 2025, the FDA issued the first CRL for the same supplemental Biologics License Application (sBLA), which aimed to extend Eylea HD dosing intervals to up to every 24 weeks across all approved indications. That letter also did not cite any issues related to clinical performance.

Catalent Receives OAI Letter from FDA

In further development, Regeneron reported that Catalent has received an Official Action Indicated (OAI) letter from the FDA, which references unresolved concerns following a general site inspection conducted in July 2025. The inspection findings are not specific to Eylea HD, but they have impacted the regulatory pathway for the pre-filled syringe.

New Submission Planned for Early 2026

As a result of the ongoing manufacturing concerns, Regeneron stated it is now targeting a January 2026 submission for an updated BLA that will include a new pre-filled syringe manufacturing filler to address the inspection-related issues.

Additional Regulatory Submissions Under Review

Despite the delay, several other regulatory submissions for Eylea HD remain under review:

• An sBLA for every-4-week dosing and for the treatment of macular edema following retinal vein occlusion (RVO) is currently being reviewed by the FDA, with a target action date in late November 2025.

• Separately, Regeneron has also submitted a request to include an additional vial filler, with the FDA expected to provide a decision by late December 2025.