The FDA issued Regeneron Pharmaceuticals, Inc. a complete response letter (CRL) stating it will not approve the Biologics License Application (BLA) for aflibercept 8 mg for the treatment of diabetic macular edema (DME), wet age-related macular degeneration (wAMD), and diabetic retinopathy (DR).
Refresh me on this drug.
Aflibercept is in a medication class of vascular endothelial growth factor A (VEGF-A) and placental growth factor (PIGF) antagonists that stops the growth of abnormal blood vessels and leakage in the eyes in patients diagnosed with retinal diseases.
Aflibercept 8 mg would be administered via intravitreal injection.
Now give me some background on it.
The high-dose drug is in joint development with Regeneron and Bayer AG; Regeneron owns exclusive rights to both Eylea (aflibercept) and aflibercept 8 mg in the United States, while Bayer has licensed the exclusive marketing rights outside of the country.
To note, both companies are currently equally splitting sales profits from Eylea and will follow suit for any future sales of aflibercept 8 mg (pending regulatory approval).
Additionally, in February 2023, the FDA accepted the companies’ BLA submission and granted aflibercept priority review.
How has it performed in clinical trials?
Two randomized trials—PULSAR (NCT04423718) study for wet AMD and PHOTON (NCT04429503) study for DME—reported positive data, with more than more than 75% of patients treated with 8 mg aflibercept were able to maintain the 12- and 16-week dosing regimens through the 48-week period (PULSAR : 79% and 77%; PHOTON: 91% and 89%).
Is that it?
More recently, Regeneron released 2-year data from the PHOTON trial that found 89% of all aflibercept-injected patients maintained ≥12-week dosing intervals.
Further, for those patients assigned to 16-week dosing regimen, 83% maintained ≥16-week dosing intervals through two years.
Gotcha. So why the rejection?
According to Regeneron, the CRL cited the FDA’s decision as solely due to an ongoing review of inspection findings at a third-party filler.
To note, the agency, “did not identify any issues with the aflibercept 8 mg clinical efficacy or safety, trial design, labeling or drug substance manufacturing.”
Is the FDA going to request more data on aflibercept?
Nope; at least, not according to Regneron: “...no additional clinical data or trails have been requested,” the company stated.
So what happens next?
Per Regeneron, the company is working closely with the FDA and the third-party filler to “to bring aflibercept 8 mg to patients with wAMD, DME and DR as quickly as possible.”So now we wait … stay tuned!