Every eye care practitioner knows the devastating effects of wet age-related macular degeneration on the visual function of our patients. AMD is the most common degenerative disease of the macula, and is the leading cause of legal blindness in the elderly population of the developed world. Evidence suggests that 10% of 65- to 74-year-olds and 30% of 75- to 85-year-olds show signs of AMD.1 The most severe manifestation of AMD is the wet form, so called because it is marked by abnormal choroidal neovascular membrane and associated vascular leak and retinal edema.
A major paradigm shift occurred with the suggestion that vascular endothelial growth factor (VEGF), known to promote both vascular growth and permeability, might be driving the abnormal choroidal neovascularization and retinal edema that leads to loss of vision in AMD.2 VEGF is a naturally occurring protein in the body. Its normal role is to trigger formation of new blood vessels (angiogenesis) supporting the growth of the body’s tissues and organs. However, in certain diseases––such as AMD––VEGF is associated with the growth of new abnormal blood vessels in the eye, which exhibit vascular permeability and lead to edema.
Approved by the FDA in 2006, intravitreal (IVT) injections of Lucentis (0.5mg ranibizumab, Genentech)—a humanized monoclonal antibody fragment that blocks VEGF—changed the standard of care for this blinding disease. Based on large pivotal studies, monthly injections of ranibizumab provide the best visual outcome and anatomic correction, and on average lead not only to maintenance of vision, but to gains in visual acuity.3
To date, the gold standard treatment for wet AMD is monthly injections of ranibizumab. However, due to the safety risks and treatment burden of monthly intravitreal injections and the rising costs, retinal specialists have been exploring other options. Physicians have attempted to decrease the safety risk and treatment burden by exploring less frequent dosing strategies and have tried to reduce the cost burden by substituting a related, off-label anti-VEGF agent: Avastin (bevacizumab, Genentech). Avastin is approved for cancer treatment and must be re-aliquoted by compounding pharmacies for eye use.
On June 17, the FDA’s Dermatologic and Ophthalmic Drugs Advisory Committee voted unanimously to recommend approval of Eylea (aflibercept ophthalmic solution, Regeneron Pharmaceuticals)—an injectible drug for the treatment of the neovascular form of age-related macular degeneration, or wet AMD. Eylea, also known as VEGF Trap-Eye, is a fully human fusion protein consisting of portions of VEGF receptors 1 and 2 that bind all forms of VEGF-A, along with the related Placental Growth Factor (PlGF). Eylea is a specific and highly potent blocker of these growth factors. The drug is specially purified and contains iso-osmotic buffer concentrations, allowing for injection into the eye.
The Eylea wet AMD regulatory submissions are based on positive results from two Phase 3 trials, the VIEW 1 and VIEW 2 studies.4 In these trials, all regimens of Eylea successfully met the primary endpoint of non-inferiority compared to the current standard of care, ranibizumab 0.5mg, dosed every month. The primary endpoint analysis was statistical non-inferiority in the proportion of patients who maintained (or improved) vision over 52 weeks compared to ranibizumab. A generally favorable safety profile was observed for both Eylea and ranibizumab. The most frequent ocular adverse events were conjunctival hemorrhage, eye pain, retinal hemorrhage and vitreous floaters.
With the introduction of Eylea, eye care practitioners will have another treatment option—one that does not require as many injections as Lucentis and Avastin.
The committee’s recommendation for approval is not binding on the FDA. The FDA, in its review of the biologics license application, will consider the recommendation. 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 FDA is expected to render a decision this November.
1. Phillips CO, Higginbotham EJ. Multivitamin supplements, ageing, and loss of vision: seeing through the shadows. Arch Intern Med. 2009 Jul;169(13):1180-2.
2. Adamis AP, Miller JW, Bernal MT, et al. Increased vascular endothelial growth factor levels in the vitreous of eyes with proliferative diabetic retinopathy. Am J Ophthalmol. 1994 Oct;118(4):445-50.
3. Rosenfield PJ, Brown DM, Heier JS, et al. Ranibizumab for neovascular age-related macular degeneration. New Engl J Med. 2006 Oct;355(14):1419-31.
4. Regeneron Pharmaceuticals, Inc. VEGF Trap-Eye (aflibercept ophthalmic solution) Briefing Document. Available at: www.fda.gov/downloads/AdvisoryCommittees/CommitteesMeetingMaterials/Drugs/DermatologicandOphthalmicDrugsAdvisoryCommittee/UCM259143.pdf (accessed July 2011).