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FDA has declined approval of Regeneron’s higher dose (8mg) of Eylea, understood to be a review of inspection findings at a third-party filler.

Regeneron Pharmaceuticals, Inc. (NASDAQ: REGN) has announced that the U.S. Food and Drug Administration (FDA) has issued a Complete Response Letter (CRL) for the Biologics License Application (BLA) for aflibercept (Eylea) 8mg for the treatment of patients with wet age-related macular degeneration (wAMD), diabetic macular edema (DME) and diabetic retinopathy (DR).   According to the company, the regulatory response is “solely due to an ongoing review of inspection findings at a third-party filler. The CRL did not identify any issues with the aflibercept 8mg clinical efficacy or safety, trial design, labeling or drug substance manufacturing, and no additional clinical data or trials have been requested”.  A Regeneron spokesperson declined on the identity of the filler and / or where it’s located.


Aflibercept (8mg) is being jointly developed by Regeneron and Bayer AG and Bayer has licensed the exclusive marketing rights outside of the U.S., where the companies share equally the profits from sales of Eylea and future sales of aflibercept (8mg) following any regulatory approvals.  Despite the FDA matter on the third-party filler, earlier in June, two-year top line data for aflibercept (8mg) indicated that 89% of all aflibercept (8mg) patients maintained ≥12-week dosing intervals through two years and many patients met the extension criteria for longer dosing intervals, including 43% for ≥20-week intervals and 27% for 24-week intervals.  According to the company, visual gains and safety of aflibercept (8mg) remained consistent with the established profile of aflibercept (2mg) Injection. The PHOTON trial (n=658) was a double-masked, active-controlled pivotal trial evaluating non-inferiority of aflibercept (8mg) 12-week (n=328) and 16-week (n=163), dosing regimens after three initial monthly doses compared to an 8-week dosing regimen for aflibercept Injection (n=167), after five initial monthly doses.


According to David M. Brown, M.D., FACS, Director of Research at Retina Consultants of Texas, and a trial PHOTON investigator stated, “the two-year PHOTON results certainly exceeded my expectations and indicate that the majority of patients may eventually be able to control their diabetic macular edema with as few as two or three aflibercept 8 mg injections per year, if approved by regulatory authorities, with similar excellent visual gains and a safety profile consistent with EYLEA given every 8 weeks.  Reducing the treatment burden in patients with diabetic macular edema is a critical unmet need, and the two-year PHOTON results reinforce the potential of aflibercept 8 mg to become the standard of care for the treatment of diabetic macular edema”.