FDA Does Not Approve Regeneron's High-Dose Aflibercept
Citing "an ongoing review of inspection findings at a third-party filler," the FDA declined to approve 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 Complete Response Letter (CRL), the FDA did not identify any issues with the aflibercept 8 mg clinical efficacy or safety, trial design, labeling or drug substance manufacturing, and no additional clinical data or trials have been requested, according to a company news release.
"Regeneron is committed to working closely with the FDA and the third-party filler to bring aflibercept 8 mg to patients with wet AMD, DME and DR as quickly as possible," Regeneron stated.
Regeneron's Biologics License Application (BLA) was supported by positive data from two pivotal trials—PULSAR in wet AMD and PHOTON in DME. In both trials, patients treated with aflibercept 8 mg (PULSAR n=673; PHOTON n=491) met the primary endpoint of noninferiority in vision gains for both the 12- and 16-week dosing regimens after initial monthly doses at 48 weeks compared to patients treated with an Eylea (aflibercept) injection (PULSAR n=336; PHOTON n=167) 8-week dosing regimen. Additionally, the vast majority of patients randomized to aflibercept 8 mg in both trials were able to maintain the 12- and 16-week dosing regimens to which they were respectively initiated through 48 weeks (wAMD: 79% and 77%; DME: 91% and 89%). The safety profile for aflibercept 8 mg was similar to Eylea in both trials, and consistent with the known safety profile of Eylea from previous clinical trials. Comparing aflibercept 8 mg to Eylea, ocular adverse events occurred in 31% (n=491) versus 28% (n=167) in PHOTON and 38% (n=673) versus 39% (n=336) in PULSAR, and there were no cases of retinal vasculitis, occlusive retinitis or endophthalmitis in either trial.
Aflibercept 8 mg is being jointly developed by Regeneron and Bayer AG. In the United States, Regeneron maintains exclusive rights to Eylea (aflibercept) injection and aflibercept 8 mg. Bayer has licensed the exclusive marketing rights outside of the US, where the companies share equally the profits from sales of Eylea and future sales of aflibercept 8 mg following any regulatory approvals.
Regulatory filings for aflibercept 8 mg are under review in Europe and Japan. Submissions to other regulatory authorities in additional countries are also planned.