The FDA has sent Regeneron a new company response letter (CRL) in regards to its supplemental Biologics License Application (sBLA) for pre-filled syringe (PFS) version of EYLEA HD (aflibercept injection 8 mg).
Yikes. First, though, refresh me on this drug.
Click here for everything you need to know (indications included).
For the purpose of this coverage: The therapeutic was originally granted FDA approval in August 2023 for three retinal indications.
Now to this CRL… this isn’t the company’s first, right?
Correct. Regeneron was previously issued a CRL in April 2025 in response to EYLEA HD’s original sBLA submission.
That application requested:
- An additional extended dosing interval greater than every 16 weeks for all approved indications
- The addition of a new indication and dosing schedule
- Macular edema following retinal vein occlusion, administered every 8 weeks
And what issue did the FDA have with that submission?
As we reported, the federal agency didn’t agree with one portion of this application: the company’s proposal for that additional extended dosing interval for all indications.
Also take note: The sBLA’s review deadline had originally been set for Aug. 19 (which, obviously, came and went with no update to report) and has since received a new target action date.
- But more on that later…
Interesting… so what’s this new issue?
It starts (and ends) with Regeneron’s manufacturing facility.
In its Q3 2025 earnings report, Regeneron shared that the FDA had sent an official action indicated (OAI) letter to Catalent Indiana, LLC, the manufacturing filler for the EYLEA HD sBLA.
- To note: An OAI letter is issued following a facility inspection by the FDA; this classification is one of three inspection classifications that indicate significant violations were identified and require immediate corrective action.
And in this case?
The OAI letter reportedly cited “unresolved issues related to a July 2025 FDA general site inspection” of Catalent’s facility (the specific location is unclear)
- Regeneron emphasized that this was “not specific to EYLEA HD.”
How does EYLEA HD factor in?
That’s where this CRL comes in. Sent on Oct. 27, the letter addressed EYLEA HD’s PFS syringe sBLA.
- According to Regeneron: “The sole approvability issue cited in the CRL relates to unresolved inspection findings at Catalent.”
So if the FDA’s issue isn’t related to the drug itself, what does it mean for the sBLA?
As such, the company announced plans to submit an application that will “include a new (PFS) manufacturing filler in the EYLEA HD BLA” by January 2026.
Nice! And what about that second portion of the application?
Regeneron’s request for every-4-week dosing and that additional indication (macular edema following RVO) is still under review.
The new target action date: “late November 2025.”
That’s coming up fast… any other FDA-related developments to know about?
Just one more: Regeneron also shared that it has submitted an application to include an additional vial filler for EYLEA HD—”with an FDA decision… expected by late December 2025.”
As always, stay tuned for updates on this!
*Disclaimer: The information provided in this article does not and is not intended to constitute legal advice; instead, all information, content, materials available herein are for general information purposes only.