The FDA has issued another complete response letter to Regeneron, rejecting its bid for approval of its prefilled syringe version of high-dose Eylea—again due to unresolved issues at the Indiana plant of its manufacturing partner, Novo Nordisk.
But while the company revealed the setback and reiterated its frustration over the delays that have hindered the advancement of Eylea HD, it also pointed to positive developments that could soon allow it to finally clear its recent regulatory hurdles.
Regeneron expects to apply in January 2026 for approval of an alternate facility at another third-party manufacturer to handle the production of prefilled syringes. The application would trigger a four-month FDA review, Regeneron CEO Len Schleifer, M.D., Ph.D., said Tuesday morning during the company's third-quarter conference call.
The company is also working with an alternate vial filler and has already asked the FDA to include it in another supplemental biologics license application (sBLA) for Eylea HD to treat retinal vein occlusion (RVO), which awaits a late-December decision date.
“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,” Schleifer said.
These measures could potentially free Regeneron from its dependence on Novo and its troubled facility in Bloomington, Indiana, which the Danish Pharma acquired from Catalent in late 2024. Two months ago, Regeneron revealed that, because of inspection issues at the facility, the FDA had extended its decision on two Eylea applications from August to the fourth quarter of this year.
Then, earlier this month, Novo notified Regeneron and its other contract partners that the FDA has tagged its Indiana facility with an official action indicated (OAI) label, which is the most severe of the agency’s three inspection classifications.
As for Regeneron’s long-term manufacturing plans, Schleifer added on Tuesday that the company would consider business development deals to gain the ability to make all of its own products.
Regeneron is currently expanding its campus in Tarrytown, New York, by $3.6 billion, including manufacturing. It is also building a new fill-finish facility in Rensselaer, also in the Empire State.
“We’ve been talking about the need for domestic manufacturing since 2014 in testimony before Congress,” Schleifer said. “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.”
Additionally, in April of this year, Regeneron signed a $3-billion, 10-year deal with Fujifilm for bulk drug production at its huge complex in Holly Springs, North Carolina.
Despite the delays, Eylea HD sales in the United States have trended positively, reaching an all-time high of $431 million in the third quarter. That is up from $307 million in the first quarter and $393 million in the second quarter.
The increase, however, can’t compensate for the erosion in sales of Regeneron’s original version of Eylea, which fell 41% year over year to $681 million.
The emergence of Amgen’s biosimilar Pavblu, which was launched 12 months ago, has taken a bite out of the sales of the Eylea franchise. It has also affected Roche’s Vabysmo, which has seen its sales stagnate since Pavblu’s launch.
As for Regeneron overall, sales were up 1% to $3.75 billion in the quarter, thanks largely to big gains for Dupixent, which was up 27%, and soon-to-be blockbuster Libtayo, which was up 26%.