FDA's Shift in Eylea HD Approval: Navigating the Clinical Path Ahead

Regulatory review timelines for Regeneron’s high-dose formulation of aflibercept, Eylea HD (8 mg), have been pushed to the fourth quarter of 2025 due to manufacturing issues identified during a recent FDA inspection of the company’s contract manufacturing site. The delay affects two regulatory submissions: a prior-approval supplement (PAS) for a prefilled syringe version of Eylea HD and a supplemental Biologics License Application (sBLA) seeking expanded approval for the treatment of macular edema following retinal vein occlusion (RVO), as well as broader use of monthly dosing across its approved indications.

The extended timeline comes after the FDA deemed newly submitted manufacturing information—provided in the wake of a routine inspection at Catalent Indiana LLC—to be a “major amendment” to both filings. Catalent, which was acquired by Novo Nordisk in late 2024, serves as the fill-finish site for Eylea HD’s syringe-based presentations. According to Regeneron, Novo Nordisk submitted a comprehensive response to the FDA in early August 2025, addressing the agency’s observations from the inspection.

Importantly, the delay does not impact the current availability of Eylea HD in the United States, where it remains accessible via vial administration. Eylea HD is approved for dosing every 8 to 16 weeks in wet age-related macular degeneration (AMD) and diabetic macular edema (DME), and every 8 to 12 weeks for diabetic retinopathy (DR), following three initial monthly doses.

The regulatory hiccup is the latest in a series of developments for the aflibercept franchise. In June, the European Commission granted a label extension for Eylea 8 mg in the EU, permitting extended treatment intervals of up to six months in both wet AMD and DME. By contrast, in April, the FDA issued a complete response letter (CRL) regarding Regeneron’s sBLA seeking to expand Eylea HD’s dosing schedule to include intervals of up to 24 weeks. While the CRL cited no concerns about the drug’s safety or efficacy, it signaled regulatory caution around ultra-extended dosing in the U.S. market.

Eylea HD was developed to reduce treatment burden by allowing longer intervals between injections compared to the original 2 mg formulation. Since its approval in 2023, the 8 mg version has gained traction among retina specialists, particularly for patients with persistent disease activity or who are unable to maintain frequent office visits. The pending sBLA would broaden its use further by including monthly dosing for patients who may benefit from a higher-intensity regimen.

Regeneron has emphasized that the manufacturing delay does not reflect any concern with Eylea HD’s clinical profile. Instead, the inspection at Catalent appears to have uncovered generalized issues with production processes or facility compliance—an increasingly common occurrence as the FDA sharpens its focus on contract manufacturing organizations (CMOs).

The review delays may slightly alter Regeneron’s commercial timeline but are unlikely to derail the broader trajectory of Eylea HD. With competition from biosimilars and rival agents like faricimab mounting, Regeneron has been positioning its high-dose aflibercept as a durable and versatile alternative across retinal indications.

Still, the incident serves as a reminder of the complexity of modern drug manufacturing—where regulatory success depends not only on clinical data but on the robustness of every link in the supply chain. For retina specialists and patients, the key takeaway is continuity: Eylea HD remains available in its vial form, and the company expects regulatory movement once manufacturing concerns are formally resolved.