Regeneron is having difficulties again with its manufacturing partner Novo Nordisk, reporting that it expects two FDA decisions due this month for its eye disease drug Eylea will be delayed, while another application for its cancer bispecific has received a complete response letter—again.
Problems uncovered during an FDA inspection in mid-July of Novo’s recently acquired site in Bloomington, Indiana, are causing the hold-up, Regeneron said. The issues are not specific to the manufacture of Eylea, the company added.
The production issues at the plant also led to an FDA rejection on Wednesday of blood cancer bispecific odronextamab, Regeneron said. This marks odronextamab’s third complete response letter after the FDA had blocked the CD20xCD3 bispecific antibody last year in two indications because of progress with its confirmatory trials.
Problems for Regeneron at the fill-finish facility are not new. They date to when the facility was run by Catalent, which was bought out by Novo Holdings for $16.5 billion in a deal that was completed in December of last year. The transaction included Novo Holdings’ sale of three Catalent plants—one of them the Bloomington site—to Novo Nordisk for $11 billion.
Two years ago, an FDA decision on Regeneron’s high-dose (HD) Eylea was delayed two months because of cleaning and procedural issues identified at the Bloomington plant as part of a pre-approval inspection.
Regeneron CEO Len Schleifer said during a Friday quarterly conference call that he doesn’t expect the Eylea HD delay to last long, calling the plant issues as “procedural.”
“Novo has been in communication with the FDA and expects to file its comprehensive and robust response next week,” he said. “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.”
Schleifer added that the massive facility produces products for the “vast majority of the top biopharmaceutical companies in the world,” and he wouldn’t be surprised to see the FDA reject other products that are manufactured at the site and are soon due for approval.
A Novo spokesperson confirmed that the FDA “conducted a general, routine and unannounced” inspection at the facility and a Form 483 list of inspectional observations was issued. The company also is set to send a “comprehensive” response, the spokesperson added.
The delay is another setback for Eylea, which has lost considerable market share to Roche’s Vabysmo, which racked up sales of 3.86 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.
It wasn’t all bad news, however, as U.S. sales of Eylea HD were up 29% to $393 million. They also grew sequentially by 28%. Regeneron credited demand growth of 16%, attributed in part to “physicians’ appreciation for product profile,” chief commercial officer Marion McCourt said.
The expected approvals coming for Eylea HD are for every-four-week dosing in a pre-filled syringe and for the treatment of macular edema following retinal vein occlusion.
“When we do get those label enhancements, we’ll be able to even have more of a trajectory of growth and demand,” McCourt added.
Helping Regeneron compensate for the decline of Eylea is the continued upward trajectory of Sanofi-partnered Dupixent, which gained two more FDA-approved indications in the second quarter and saw a 22% sales boost to $4.34 billion.
Regeneron reported sales in the quarter at $3.68 billion, good for 4% increase year over year and 21% boost sequentially.