The FDA has extended the target action dates for two regulatory applications submitted by Regeneron Pharmaceuticals, Inc. to expand the dosing schedule and indications for EYLEA HD (aflibercept) injection 8 mg, as well as for a pre-filled syringe (PFS) version of the product.
First, an EYLEA HD refresh.
What it is: A vascular endothelial growth factor (VEGF) inhibitor that contains 8 mg aflibercept administered via intravitreal (IVT) injection.
Take note: This dosage differs from the company’s EYLEA 2 mg injection, which is FDA-approved and indicated for four retinal diseases—including (most recently) retinopathy of prematurity (ROP).
EYLEA HD’s indications: Jointly developed by Regeneron and Bayer AG (owner of its exclusive marketing rights outside the U.S.), EYLEA HD was granted FDA approval in August 2023 for three retinal indications:
- Diabetic macular edema (DME)
- Dosing: Every 8 to 16 weeks (2 to 4 months)
- Diabetic retinopathy (DR)
- Dosing: Every 8 to 12 weeks (2 to 3 months)
- Wet age-related macular degeneration (AMD)
- Dosing: Every 8 to 16 weeks (2 to 4 months)
Now to these regulatory applications.
We’ll start with the company’s supplemental Biologics License Application (sBLA)—different from a BLA—which seeks to:
- Add macular edema following retinal vein occlusion (RVO) as a new indication
- Including a proposed every 8 weeks dosing schedule
- Update EYLEA HD’s dosing schedule for its proposed and current indications:
- Proposed: Dosing every 4 weeks (monthly, in other words) for all indications excluding ROP
What’s included in this sBLA?
Accepted by the FDA for priority review in April 2025, the application features clinical findings from the phase 3 QUASAR trial to support EYLEA HD’s macular edema following RVO indication.
- See here for our coverage on that data.
However: Just days after accepting the app, the FDA sent Regeneron a company response letter (CRL).
- Its reasoning: The agency did not agree with the company’s proposal for an additional extended dosing interval that was greater than every 16 weeks. Read up on this.
Notably: No issue was taken with the company’s proposed new indication.
Gotcha. And what was the initial review deadline for the application?
Aug. 19.
To note: This target action date was set following Regeneron’s use of a priority review voucher (PRV).
Now to the second submission you referenced.
That would be a chemistry, manufacturing and controls (CMC) prior-approval supplement (PAS).
What this is: An FDA submission for a significant adjustment to an approved drug product (such as EYLEA HD) with a substantial potential impact on the product’s quality, safety, or effectiveness.
And in Regeneron’s case: The company filed an application for the use of EYLEA HD PFS in Q1 2025.
- Notably: The target action date for this app was also in August 2025.
Got it. So why was an extension needed?
Importantly: Regeneron noted in its Q2 2025 earnings call at the beginning of August that the delay and subsequent extended review period for both applications were expected.
The reason: Is reportedly related to the FDA’s observations from a July 2025 site inspection (Catalent Indiana LLC, acquired by Novo Nordisk A/S in December 2024) at the filler for EYLEA HD.
And did Novo respond to those observations?
Indeed. Per Regeneron, Novo reportedly submitted a "comprehensive response” to the FDA earlier this month to address the issues raised by the agency.
So what’s the updated timeframe for this review?
As Regeneron shared: “It is our understanding that the FDA will be able to act expeditiously on these applications once the manufacturing issues have been resolved.”
In other words: The updated review period’s end date is still to be determined.