Regeneron Pharmaceuticals, Inc. announced the FDA issued a complete response letter (CRL) concerning the supplemental Biologics License Application (sBLA) for EYLEA HD (aflibercept) injection 8 mg.
This news comes just days after announcing the federal agency had accepted its sBLA for priority review.
Where to begin?
First, we’ll get into this CRL.
According to Regeneron, the FDA issued the letter in regard to the company’s request for adding extended dosing intervals (up to every 24 weeks) for the FDA-approved EYLEA HD across all of its approved indications.
To refresh, those indications include:
- Wet age-related macular degeneration (AMD)
- Current dosing schedule: Every 8 to 16 weeks
- Diabetic macular edema (DME)
- Current dosing schedule: Every 8 to 16 weeks
- Diabetic retinopathy (DR)
- Current dosing schedule: Every 8 to 12 weeks
So what’s the reason for this rejection?
The agency emphasized that its rejection was not based on any issues with EYLEA HD’s safety or efficacy for its already-approved indications and dosing schedules—in fact, none were identified.
Instead: The FDA reportedly did not agree with the company’s proposal for an additional extended dosing interval that was greater than every 16 weeks (which, Regeneron noted, “is the maximum dosing interval currently indicated in the label”).
Gotcha. Now let’s backtrack a moment on this sBLA. Wasn’t there more to it?
Indeed there was. The company also asked the FDA to add to EYLEA HD’s prescribing information (PI) a new indication (and, in turn, a new dosing schedule to accompany it).
- That indication: Macular edema following retinal vein occlusion (RVO)
- Its dosing schedule: Every 8 weeks
Did the FDA have anything to say about that part of the sBLA?
As far as we know, no, it did not. Regeneron’s report of the CRL appeared to be strictly limited to the agency’s decision on its expanded dosing request for those already-approved indications.
What this means: The FDA’s previously set review deadline for that portion of the sBLA (which, keep in mind, was accepted for priority review) should still be in effect.
That date: Aug. 19, 2025
Interesting … so has the company responded to the CRL yet?
Not quite. In announcing its receipt of the letter, Regeneron stated it’s currently evaluating the federal agency’s decision and “will determine a path forward in due course.”
Give me the big picture of this.
In general, the FDA sends a CRL when it has identified concerns that prevent it from approving an application (such as an sBLA, BLA, or new drug application) in its current form.
More specifically: The letter will detail specific deficiencies—ranging from minor (such as labelling issues) to major (such as a need for more clinical data)—in a company’s application that are preventing the agency from approving it, as well as recommendations for how each can be addressed.
- Notably: In Regeneron’s case, all we know so far is that the FDA did not agree with the company’s proposal for an additional extended dosing interval that was > every 16 weeks.
And keep in mind: This is not necessarily a full rejection of an application but rather an indication that it is not yet ready for regulatory approval.
And in Regeneron’s case?
The company now has the opportunity to revise EYLEA HD’s sBLA (based on the FDA’s feedback) and resubmit for regulatory review.
And you know what that means—now we wait for updates.