The US Food and Drug Administration (FDA) has delayed decisions on two regulatory applications that would expand the use of Regeneron’s Eylea HD (aflibercept), dashing the company’s hopes of promptly bolstering the franchise’s reach amid biosimilar entries.
The FDA, which was originally going to make a decision by 19 August, has now pushed the target action dates back to Q4 2025.
Regeneron is hoping to win approval for a prefilled syringe version of Eylea HD, along with gaining 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. Following three initial monthly doses, the drug’s current dosing period is every eight to 16 weeks or every eight to 12 weeks, depending on the indication.
The delay does not come as a surprise. During its Q2 earnings call, Regeneron disclosed that issues at a filling site for Eylea HD meant regulatory delays were anticipated. The problems occurred at Novo Nordisk’s plant in Bloomington, Indiana. The Danish drugmaker bought the site from CDMO giant Catalent as part of a $16.5bn acquisition in December 2024.
Regeneron uses the site for filling vials of Eylea, the pharma company’s lead ophthalmologic drug. However, the company said the issues were not specific to Eylea’s production, with the same manufacturing issues leading to an FDA rejection last month for Regeneron’s blood cancer bispecific antibody candidate odronextamab.
During the Q2 earnings call on 1 August, Regeneron CEO Len Schleifer played down the severity of observations made during the FDA inspection.
Schleifer commented that the FDA did not request structural changes, adding that the “procedural” issues will not last long.
At the time, Novo Nordisk said in an emailed statement to Pharmaceutical Technology: “We take all observations seriously and have initiated a thorough review of our processes and procedures. A comprehensive response will be implemented to address the Form 483 observations promptly and holistically. We welcome FDA inspections as we aim to ensure continuous improvement and, ultimately, ongoing patient safety.”
In a 20 August release, Regeneron confirmed that Novo Nordisk has since submitted a comprehensive response to address the observations noted by the FDA.
Though a fast resolution is expected by Regeneron, it further delays the pharma company’s efforts to strengthen the Eylea brand. Eylea HD, the high-dose version, is viewed as the successor to Eylea – the latter’s sales have dropped sharply over recent years. It is co-commercialised with Bayer, which holds rights to the vascular endothelial growth factor (VEGF) inhibitor outside the US.
Regeneron’s position in the eye disease market has been significantly eroded by Roche’s rival drug Vabysmo (faricimab). Eylea’s sales dropped 39% to $754m in the US in Q2, meaning it has now lost blockbuster status in the country, though the revenue drop was also caused by the pickup in sales of its high-dose version.
Regeneron hopes Eylea HD – whose sales grew 29% this quarter – will help the company regain market share from Roche. Despite mixed results for its Eylea brand, Regeneron’s total Q2 sales grew 4% to $3.68bn.
Before Novo arrived as its owner, issues at the Bloomington facility caused a two-month delay for Eylea HD’s FDA approval decision in 2023. In November 2024, the FDA also found quality control lapses at the facility, including the discovery of a “pest” on the manufacturing line.
The filling plant, which has a total area of 950,000ft², has received sizeable investments over the past few years for expansion. The site is the main supplier of fill-finish work for Novo Nordisk’s billion-dollar weight loss drug Wegovy (semaglutide).
