At issue is an ongoing review of inspection results from a third-party filling company. No issues were cited in the FDA’s complete response letter about clinical efficacy or safety.
The FDA has issued a complete response letter (CRL) for a higher dose regimen of Eylea (aflibercept). Developed by Regeneron Pharmaceuticals and Bayer, Eylea is approved in a 2 mg dose to treat patients with wet age-related macular degeneration (wAMD), diabetic macular edema (DME) and diabetic retinopathy (DR), as well as a 0.4 mg dose to treat retinopathy of prematurity. The companies were seeking an 8 mg dose to treat age-related macular degeneration, diabetic macular edema and diabetic retinopathy.
The CRL was issued related to an ongoing review of inspection findings at a third-party filer. Regulators did not identify any issues with the Eylea 8 mg clinical efficacy or safety, trial design, labeling or drug substance manufacturing, and no additional clinical data or trials have been requested.
At the same time, Regeneron released two-year data from a study evaluating the higher dose in patients with diabetic macular edema. In these patients, Eylea 2 mg is administered every four weeks for the first five injections and then every eight weeks. In the trial with the 8 mg dose, patients were given Eylea every 12 weeks or 16 weeks. The results indicated that patients maintained visual gains and safety was consistent with the original dose.
“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,” David M. Brown, M.D., FACS, director of research at Retina Consultants of Texas and a trial investigator, said in a press release.
The BLA for the higher dose was accepted by the FDA for priority review in February and was supported by two studies: PULSAR in wet AMD and PHOTON in DME. In both trials, patients treated met the primary endpoint of non-inferiority in vision gains for both the 12- and 16-week dosing regimens after initial monthly doses at 48 weeks with those given the 2 mg dose.