Regeneron receives another CRL for its Eylea 8 mg

Regeneron has once again received a complete response letter (CRL) from the US Food and Drug Administration (FDA) for the company’s request for approval of its prefilled syringe option of high-dose (HD) Eylea (aflibercept) 8 mg.¹

The FDA cited unresolved issues at the Bloomington, Indiana, plant of Novo Nordisk, Regeneron’s manufacturing partner, as the reason for issuing the latest CRL.¹ In August of 2025, Regeneron announced the FDA rejected a new blood cancer therapy due to problems at this same Novo Nordisk-owned site.²

In August, it was revealed that the quality control lapses were found in November 2024, which included finding a “pest” on the manufacturing line.²

The FDA tagged Novo’s Indiana facility with an official action indicated (OAI) label, a press release said.¹ OAI is the FDA’s most severe of its three inspection classifications, which Novo notified Regeneron of earlier this month.¹

In January 2026, Regeneron is expected to apply for approval of an alternate facility at another third-party manufacturer to produce the prefilled syringes.¹ The January application for approval will trigger a four-month FDA review.¹

According to Regeneron CEO Len Schleifer, Regeneron has long-term manufacturing plans that consider business development deals that work toward the goal of the company making all its own products.¹

“We’ve been talking about the need for domestic manufacturing since 2014 in testimony before Congress,” Schleifer said in a press release.¹

“One piece of the whole puzzle that we do not have adequate positioning in is the filling, but I’m pleased to say that we would expect our filling plant, which we’ve invested quite a bit in, it’s now ready to go, and we expect it to come online in the coming year.”

Through $3.6 billion, Regeneron is expanding its Tarrytown, New York, campus, including manufacturing; additionally, a new fill-finish facility is being built in Rensselaer, New York.¹

This recent CRL follows a CRL issued in April of 2025 in which the FDA said it did not agree with the supplemental biologics license application (sBLA) of the company for the addition of extended dosing intervals.³

“This would provide an additional opportunity for the FDA to approve the sBLA for every four-week dosing and RVO, given we believe there are no other outstanding review issues for this application,” Regeneron CEO Len Schleifer said of the CRL in a recent press release.¹

At the time of this press release, Regeneron noted in its Q3 2025 financial and operating results that the company has another sBLA under review for Eylea HD for an every-four-week dosing schedule for the treatment of retinal vein occlusion (RVO).⁴

Currently, aflibercept 8 mg is approved with dosing intervals every 8 to 16 weeks for the treatment of wet age-related macular degeneration (wAMD) and diabetic macular edema (DME), as well as dosing every 8 to 12 weeks for the treatment of diabetic retinopathy (DR), following 3 initial monthly doses.³

According to previous reporting from Ophthalmology Times, in March 2024, Regeneron published 1-year results of its PULSAR and PHOTON trials evaluating aflibercept 8 mg for the treatment of wAMD and DME.³ It was found that the 8 mg dosage was noninferior and demonstrated clinically equivalent visual gains at 48 weeks for both the 12- and 16-week dosing regimens.³

Reference:

1. Dunleavy K. Regeneron reports another manufacturing-related rejection for Eylea HD, but says help is on the way. Fierce Pharma. Published October 28, 2025. Accessed October 29, 2025. https://www.fiercepharma.com/manufacturing/regeneron-reports-another-manufacturing-related-crl-eylea-hd-says-help-way

2. Barrie R. Manufacturing issues at Novo facility disrupt Regeneron drug review. Pharmaceutical Technology. Published August 4, 2025. Accessed October 29, 2025. https://www.pharmaceutical-technology.com/news/manufacturing-issues-at-novo-facility-disrupt-regeneron-drug-review/?cf-view

3. Harp MD, Hayes H, Filkins K. Regeneron announces FDA issues CRL for aflibercept 8 mg (Eylea HD) sBLA. Ophthalmologytimes.com. Published April 21, 2025. Accessed October 29, 2025. https://www.ophthalmologytimes.com/view/regeneron-announces-fda-issues-crl-for-aflibercept-8-mg-eylea-hd-sbla

4. Regeneron Reports Third Quarter 2025 Financial and Operating Results | Regeneron Pharmaceuticals Inc. Regeneron Pharmaceuticals Inc. Published 2025. Accessed October 29, 2025. https://investor.regeneron.com/news-releases/news-release-details/regeneron-reports-third-quarter-2025-financial-and-operating