FDA Rejects Regeneron’s Higher Dose Eylea Treatment

Due to an ongoing review of inspection findings at a third-party filler, the FDA has rejected Regeneron's aflibercept 8 mg for the treatment of patients with wet age-related macular degeneration (AMD), diabetic macular edema (DME), and diabetic retinopathy (DR).

In a communication known as a Complete Response Letter (CRL), the FDA did not raise any concerns regarding the clinical efficacy, safety, trial design, labeling, or drug substance manufacturing of aflibercept 8 mg. The FDA did not request any additional clinical data or trials, as stated in a news release by the company.

Regeneron expressed its commitment to collaborating closely with the FDA and the third-party filler to expedite the availability of aflibercept 8 mg to patients with wet AMD, DME, and DR.

Regeneron's submission of the Biologics License Application (BLA) was based on positive data from two pivotal trials: PULSAR, conducted for wet AMD, and PHOTON, conducted for DME. In both trials, patients who received aflibercept 8 mg (PULSAR: n=673; PHOTON: n=491) met the primary endpoint of noninferiority in terms of vision gains for both the 12- and 16-week dosing regimens. These dosing regimens followed initial monthly doses over a span of 48 weeks, in comparison to patients treated with an 8-week dosing regimen of Eylea (aflibercept) injection (PULSAR: n=336; PHOTON: n=167).

Furthermore, the majority of patients randomized to receive aflibercept 8 mg in both trials were able to maintain the respective 12- and 16-week dosing regimens throughout the 48-week period (wAMD: 79% and 77%; DME: 91% and 89%). The safety profile of aflibercept 8 mg was similar to that of Eylea in both trials and consistent with the known safety profile observed in previous clinical trials of Eylea. When comparing aflibercept 8 mg to Eylea, ocular adverse events were reported in 31% (n=491) versus 28% (n=167) in PHOTON and 38% (n=673) versus 39% (n=336) in PULSAR. Notably, neither trial reported any cases of retinal vasculitis, occlusive retinitis, or endophthalmitis.

Aflibercept 8 mg is a collaborative development effort between Regeneron and Bayer AG. Within the United States, Regeneron holds exclusive rights to Eylea (aflibercept) injection and aflibercept 8 mg. Outside the US, Bayer has obtained exclusive marketing rights. The profits from sales of Eylea and potential future sales of aflibercept 8 mg, following regulatory approvals, are shared equally by the two companies.

Regulatory filings for aflibercept 8 mg are currently undergoing review in Europe and Japan. Moreover, plans are in place to submit applications to other regulatory authorities in various additional countries.

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