FDA Panel Recommends Approval of Aflibercept for Wet AMD

Mark Crane

June 20, 2011

June 20, 2011 — A US Food and Drug Administration (FDA) advisory panel has voted unanimously to recommend approval of aflibercept ophthalmic solution (Eylea, Regeneron Pharmaceuticals Inc), an injectable drug for the treatment of the neovascular form of age-related macular degeneration (wet AMD).

The FDA's Dermatologic and Ophthalmic Drugs Advisory Committee voted 10 to 0 on June 17 in favor of aflibercept, after a day-long meeting.

The aflibercept wet AMD regulatory submissions are based on the positive results from a couple phase 3 trials — the VIEW 1 study and the VIEW 2 study — the manufacturer said. In these trials, all regimens of the drug, including 2 mg dosed every 2 months (after 3 loading doses), successfully met the primary endpoint of noninferiority compared with the current standard of care, ranibizumab (Lucentis, Genentech), 0.5 mg dosed every month, which is currently the most potent treatment option for wet AMD. The primary endpoint analysis was statistical noninferiority in the proportion of patients who maintained (or improved) vision over 52 weeks compared with ranibizumab.

FDA staff, in a document released earlier last week, said a generally favorable safety profile was observed for both aflibercept and ranibizumab and that aflibercept was effective in treating AMD, the leading cause of blindness in the elderly. The most frequent ocular adverse events were conjunctival hemorrhage, macular degeneration, eye pain, retinal hemorrhage, and vitreous floaters.

"The positive recommendation by the advisory committee is an important step toward providing wet AMD patients with a new treatment option that could potentially reduce the burden that exists with current therapies," said George D. Yancopoulos, MD, PhD, president of Regeneron Research Laboratories, in a news release. "We look forward to continuing to work with the FDA as it completes its evaluation."

Vascular endothelial growth factor (VEGF) is a naturally occurring protein in the body. Its normal role in a healthy organism is to trigger formation of new blood vessels (angiogenesis) supporting the growth of the body's tissues and organs, the company said. However, in certain diseases, such as AMD, it is also associated with the growth of abnormal new blood vessels in the eye, which exhibit vascular permeability and lead to edema.

Aflibercept, also known as VEGF Trap-Eye, is a fully human fusion protein consisting of portions of VEGF receptors 1 and 2, which binds all forms of VEGF-A, along with the related placental growth factor. Aflibercept is a specific and highly potent blocker of these growth factors. It is specially purified and contains iso-osmotic buffer concentrations, allowing for injection into the eye.

The committee's recommendation for approval is not binding on the FDA. The recommendation will be considered by the FDA in its review of the biologics license application. Regeneron submitted a biologics license application for marketing approval in wet AMD in the United States in February and received a priority review designation. The target date for an FDA decision is August 20, the company said in a news release.

Regeneron and Bayer HealthCare are collaborating on the global development of aflibercept for the treatment of wet AMD, central retinal vein occlusion, diabetic macular edema, and other eye diseases and disorders. Bayer submitted an application this month for marketing authorization of aflibercept in Europe for wet AMD.

Bayer HealthCare will market aflibercept outside the United States, where the companies will share equally the profits from any future sales. Regeneron maintains exclusive rights to market aflibercept in the United States.