The hits just keep on coming for Regeneron’s Eylea franchise.
Wednesday, the FDA extended its target action dates for two applications to expand the use of Eylea’s high-dose formulation. The U.S. regulator was originally scheduled to make its Eylea HD decisions by Aug. 19, but it has now has pushed those back to the fourth quarter, Regeneron said.
The delay was not unexpected. During its second-quarter earnings presentation three weeks ago, Regeneron revealed that problems were identified in a general FDA inspection of its third-party contract manufacturer. The issues were uncovered at Novo Nordisk's fill/finish facility in Bloomington, Indiana, and were not specific to the manufacture of Eylea, Regeneron said.
The production issues at the plant also led to an FDA rejection last month of blood cancer bispecific odronextamab, Regeneron said.
Novo Nordisk, which recently acquired the Indiana facility from Catalent, submitted a “comprehensive response,” to the FDA observations earlier this month, Regeneron said Wednesday.
“It is our understanding that the FDA will be able to act expeditiously on these applications once the manufacturing issues have been resolved,” the company added in its release.
“Based on our review of the observation and Novo’s proposed response—along with the progress that we have made with alternate third-party fillers—we anticipate an expeditious resolution of our filling issues for Eylea HD,” Regeneron CEO Len Schleifer, M.D., Ph.D., said during the second-quarter presentation.
Regeneron is seeking approval for a Chemistry, Manufacturing and Controls (CMC) Prior-Approval Supplement (PAS) for the Eylea HD prefilled syringe, as well as a supplemental Biologics License Application (sBLA) seeking approval for both the treatment of macular edema following retinal vein occlusion (RVO) and the broadening of the dosing schedule to include every 4-week (monthly) dosing across approved indications.
Eylea HD is available in the U.S. through vial administration. It is approved with dosing intervals from every eight to 16 weeks for patients with wet age-related macular degeneration and diabetic macular edema. It also is endorsed for dosing every eight to 12 weeks for patients with diabetic retinopathy.
Regeneron’s issues with the manufacture of Eylea HD extend to two years ago, when the FDA delayed its decision on the approval of the 8-mg formulation by two months because of cleaning and procedural issues identified at the Bloomington plant, then run by Catalent, as part of a preapproval inspection.
After dominating the market with megablockbuster Eylea, Regeneron has had difficulty making the most of its high-dose formulation. In April of this year, the FDA rejected Regeneron's request to extend its dosing of Eylea HD to every 24 weeks.
The delay is another setback for the Eylea franchise, which has lost considerable market share to Roche’s Vabysmo, which racked up sales of 3.86 billion Swiss francs ($4.25 billion) in 2024 in just its second full year on the market.
Since Vabysmo’s approval in 2022, Eylea’s sales have taken a major hit, especially in the U.S. In the second quarter, Regeneron reported the Eylea franchise generated revenue of $1.15 billion, down 25% year over year.