The US Food and Drug Administration (FDA) has rejected a prefilled syringe version of Regeneron's ophthalmology blockbuster Eylea HD (aflibercept), as manufacturing shortcomings continue to plague the pharma company.

Announcing the setback in its Q3 earnings, Regeneron said that the authority issued a complete response (CR) letter for Eylea HD’s pre-filled syringe supplemental biologics licence application (sBLA).

The sole reason for the rejection was unresolved issues at a facility of its manufacturing partner, Novo Nordisk. The FDA uncovered problems during an inspection of Novo Nordisk’s filling plant in Bloomington, Indiana, reported by Regeneron in August 2025. Novo acquired the Indiana plant as part of its $16.5bn acquisition of CDMO Catalent in December 2024.

Shortcomings at the facility, which is used to fill vials of Eylea, delayed the FDA’s approval decision for the prefilled syringe version in mid-August.

Earlier this month, Novo’s Indiana facility was hit with an official action indicated (OAI) label – the most severe of the agency’s three inspection classifications, reflecting an “unacceptable state of compliance”.

Despite a manufacturing issue-laden path to approval, hope could be on the horizon for Eylea HD’s expansions. Regeneron has decided to look elsewhere for an alternate facility, with the company planning to submit a new application using a new pre-filled syringe manufacturing filler in January 2026.

On a Q3 conference call, Regeneron CEO Len Schleifer said: “We continue to execute on our previously announced plan to submit an application to add an alternate prefilled syringe filler by January 2026, which would trigger a four-month FDA review.”

Eylea HD is already FDA-approved to treat wet age-related macular degeneration (wet AMD), diabetic macular oedema, and diabetic retinopathy. Regeneron is also hoping to gain a new disease indication in the form of macular oedema following retinal vein occlusion (RVO) and the broadening of the dosing schedule to include every four weeks across approved indications.

This sBLA is still under review by the FDA, with a target action date in late November 2025. In addition, Regeneron has submitted an application to include an additional vial filler, with an FDA decision regarding this expected by late December 2025.

Eylea HD, the high-dose version of Eylea, is a major growth driver for Regeneron. Sales for both versions of Eylea totalled $1.1bn in the US in Q3 2025, up 28% from Q3 2024. Regeneron has US rights to the drug while Bayer commercialises it elsewhere.

Regeneron has been trying to shift its patient base to Eylea HD, which allows longer intervals between injections. Pre-filled syringes would further bolster the franchise with more efficient administration.

The move to increase Eylea HD uptake comes as Regeneron’s position in the eye disease market has been significantly eroded by Roche’s rival drug Vabysmo (faricimab). Multiple Eylea biosimilars have also flooded the US market amid patent exclusivity loss, which has exerted further pressure on the brand.

Schleifer added: “We continue to believe that future product enhancements such as a four-week dosing interval, the inclusion of macular oedema following retinal vein occlusion, or RVO, and a prefilled syringe administration are needed to fully unlock Eylea's HD commercial potential.”

Boosting filling capacity

Regeneron has been busy expanding its corporate and research headquarters in Tarrytown, New York. The company is investing nearly $3.6bn in the expansion, which includes a new fill/finish manufacturing facility in Rensselaer. Regeneron also signed a deal worth more than $3bn with contract drug developer Fujifilm Diosynth in April 2025, bringing its total investments in the country to exceed $7bn.

“We’ve been talking about the need for domestic manufacturing since 2014 – we [already] mentioned the over $7bn investment plan,” Schleifer added.

"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 to come, which we've invested quite a bit in, it's now ready to go, and we expect it to come online during the coming year.”